DIP Episode 380 - USMLE Step 2CK/3 Rapid Review Series 72

Okay, welcome to episode 380 of the Divine Intervention Podcasts. My name is Divine and in today's podcast, we will be continuing the Rapid Review series for the USMELIS step 2 CK slash step 3 exams. This is going to be series 72. So, if you are taking your USMELIS step 2 CK or step 3, or complex level tour 3 exams, within the next one month, I will encourage you to sign up for the courses I have next week. I start off with an MBME Testicking Strategy course on Monday, and then I continue that with a 24 hour review course from Tuesday to Friday. We'll meet for six hours each day. There's many people that have taken these courses that have done extremely well on the exams. I see people, they take the Testicking Strategy course, and they say, wow, my Q Bank percentage is shut up after I took the course, or wow, my practice test course improved by 20, 30, 40 points after I took the course. Again, the review course is a very high level review course, really helpful for tons of people again. I've had tons of people take each of these courses and they've done really well on the exams. And then if you're looking ahead to step 2 CK step 3 in the summer, now that the match cycle is effectively over, I have a 40% step 2 CK slash step 3 school. Obviously, it's going to apply to people taking complex level tour 3 as well. It's going to be taking place from May 2 to May 13, 2022. The course is, you know, it's 75 hours long, but it's going to be like a big time review.

I literally made a podcast specifically on that, I will encourage you to check that podcast out. But what I will say is, it's going to be a 40% cup, because again, I want to really invest deeply in everyone that's attending. But if you attend it, you're not going to have a bad time. You're going to have a wonderful time. You're going to learn a lot in many different ways, in many different dimensions. The goal of that course is to prepare you like extremely well for step 2 CK or step 3, a complex level tour 3. Okay, so let's just jump right into it. So if you're interested in any of these things, just shoot me an email through the website. And I'll give you some more information on cost, on how to register and things like that. So what if they give you a question about a 55-year-old guy, the tell you that for the last three days, he has been having been in his thumb. And then you notice that you see some vesicular lesions under his, like around his nail food on his right thumb. And then they say what's your next step in management? Well, I would really hope that your next step in management is to go ahead and give the person a cyclover. Right? Oral, a cyclover. Right? So this person obviously has herpetic weight low. Herpetic weight low is treated with oral, a cyclover. They may try to trick you on the exam into giving IV a cyclover. You don't give IV a cyclover for herpetic weight low. Right?

Again, one concept I guess that is high to understand for exams is when you give oral, versus IV therapy. It's not everybody that gets IV therapy. Usually people that get IV therapy are people that fall into two categories. One, people that have very severe illness, right? They're like, he more than a million stable or, you know, they are super fraberal or they have like a powerful lucho cytosis and organ damage. And then the second group of people that get IV therapy are people that get people that cannot tolerate oral intake. So when I say to you, those are really the only two people that should ever get IV therapy on NV Me exams. If you're given IV therapy to people that should be getting oral therapy, in fact, the NV Me is they do this from time to time. When you put the same answer, they'll put the oral formulation of the drug and then they'll put the IV formulation of the drug. Again, you need to keep some of these principles in mind as you make these judgment calls on exams. So we know that, obviously, right? Herpanic weight loss caused by the Herpes virus, right? Remember, the Herpes virus causes many different problems, right? So it can cause, you know, the general infection, right? Which again, it's also treat all these cyclovere, right? But it can also cause the oral infection, right? Herpes libyalis, right? Again, both of these things can treat all these cyclovere, right? And many of these things tend to be reactivations of disease, right?

Now, remember that Herpes can also cause many injilies, right? Typically, remember, if Herpes wants to torture a person's brain, it's going to go after the temporal lobes, right? And many times, those people are going to have hemorrhagic lumbar punctures, right? So you check the CSF and you're going to be seeing, like, hundreds, sometimes thousands of red blood cells, right? Yes, you can have that in a sub-acnoid hemorrhage, right? But you can also certainly have that in a person that has, like, Herpes are meningitis, right? So remember, just keep those things in mind with Herpes, for example, right? So how does the cyclovere work? Or remember, the cyclovere is a DNA polymerase inhibitor. Now, I want to explain something to you here. The MBM Es, they love to do this thing where, again, and this is something I emphasize heavily in my test-taking strategies class and in my review courses, that the MBM Es these days, the answers you're expecting to the questions you read, and not the answers you're going to see on your exam. The thing the MBM Es love to do is, again, they're just trying to push things a step further. They're trying to see people that actually study them, people that actually understand things instead of just blindly memorizing things. So again, they put these things I call derivative answers on exams, where it's something you know, but you just put it in different terms. So that's something you want to be mindful of as you study for your exam, right?

So, like, for example, instead of putting a cyclovere as an answer, they can put, if they want to make an easier answer, or let me not say an easier answer, it's likely harder answer, will be a DNA polymerase inhibitor. But one thing that the MBM Es love to do these days is that they love to instead use this term, right? So, let me explain first. Instead of putting DNA polymerase inhibitor, the older other puts the answer that says inhibitor of a DNA dependent DNA polymerase. So, you need to be like divine. Are those not different terms, DNA polymerase inhibitor versus inhibitor of a DNA dependent DNA polymerase? No, they're the same term, right? Because what does DNA polymerase do? DNA polymerase uses DNA as a template, and then its output is DNA. So, DNA polymerase itself is DNA dependent, right? So, it's dependent on the template, it's DNA dependent, and then it makes DNA, it's a DNA polymerase, right? It's cyclovere and GAN cyclovere. Remember GAN cyclovere is not for herpes, it's more for CMV, although CMV is one of the herpes viruses, right? So, what GAN cyclovere is also a DNA polymerase inhibitor, it inhibits a DNA dependent DNA polymerase. Okay, but now, let's maybe try something else. What if we look at the HIV drugs, right, that are NRT Is or NRT Is? Remember, NRTI means nucleoside reverse transcripties inhibitor. NRTI means, you know, non-nucleoside reverse transcripties inhibitor. Well, let's ask ourselves, what in the world does reverse transcripties mean?

Or what does, what in the world does reverse transcripties do? Well, remember, reverse transcripties is an enzyme, right? Because remember transcription is where you go from DNA to RNA. So, reverse transcription is where you go from RNA to DNA, right? So, that means reverse transcripties uses an RNA template to produce DNA, right? It's that DNA of HIV that then integrates into the genome, right? And that's usually done by the integrates enzyme, right? So, if you think about it, since RNA, sorry, since reverse transcripties uses RNA as a template and makes DNA as its output. On an NBM exam, they can give you a HIV question. Instead of saying, or administer reverse transcripties inhibitor, they can put in the answer that says inhibitor of an RNA dependent DNA polymerase, right? I'll say that again, inhibitor of an RNA dependent DNA polymerase, because it depends on RNA as the template, what it produces DNA as its output, right? Another classic question they can write in this vein is they can give you a question about a person that has TB, right? And then they tell you that, well, the person is having these orange secretions, these red secretions, red tears, urine, earwax, right? And then they say, which of the following agents is most likely responsible for the following side effects? Well, remember that the agent that is responsible is rifamping.

But again, instead of putting rifamping, one smart thing our friends at the NBM is can do is that they will write RNA polymerase inhibitor. Okay? Well, if they want to make the question a little more challenging, they will put DNA dependent RNA polymerase inhibitor, and inhibitor of DNA dependent RNA polymerase activity, right? Because again, an RNA polymerase uses DNA as its template, and then it produces RNA as its output, right? So whenever you see a drug that is a DNA polymerase inhibitor, while RNA polymerase inhibitor, or a restaurant's cryptase inhibitor, I will encourage you to try to just think through and be able to express it in this X, Y, Z dependent, X, Y, Z polymerase template that I'm explaining to you right now. I know I may be like, wow, divine. You're explaining an inordinate amount of time on this. But this stuff is extremely high yield for the test. Right? Now, what if they give you a question about a patient? And they tell you that the patient, you know, was admitted to the hospital a few weeks ago for an infection, for kidney infection, and then they took an antibiotic. Well, then now, you know, a few weeks later, they have to crank up their televisions all the way up to be able to hear a thing. What antibody do those people take? Well, really, you're saying divine. This person likely took gentamisin, right? Likely took an amino glycoside, right? So I know some of you may be like, wow, divine. Yes, I get it.

Gentamisin, you know, the amino glycosides, they are auto toxic. But why didn't you pick vancomycin as your answer? In fact, let me tell you this. Friends at the NBM means, right? The smart thing that you would do to be honest with you, any smart question writer will put vancomycin as an answer. Because vancomycin is also auto toxic, right? And so of you may be like, wow, divine. That's very evil of you. How can you be suggesting that we put vancomycin as an answer? And we put gentamisin as an answer. The thing is, whenever they give you two answers, that's a fight for a question. Right? Many times none of those will be right. Or there is a differentiating factor that has been placed in the question that will help you pick one from the other. Right? So there is a differentiating factor in this veneer that I gave you that I would hope will make you not pick vancomycin and make you pick more an amino glycoside. Because think about it, I said that the person had an infection. If I missed it, my apologies, but let's say they had a kidney infection. Kidney infections are caused almost exclusively by gram negative organisms. Right? Don't get me wrong. You know, stuff's uprofidicose, gram positive can cause some issues. But for the most part, you're looking at an equal line, things like that. Well, if you want to cover gram negatives, you're going to be using an amino glycoside. Right? You're going to be using vancomycin to cover gram negatives.

Vancomycin almost exclusively covers only gram positive infections. Right? So if it was a gram negative, if it was a kidney infection or a ut, if it was a gram negative, it would be a gram negative. So if you want to cover gram positive, you're going to be using an amino glycoside. Remember, the amino glycosides are never toxic. Right? But they are also auto toxic. Right? Now, don't forget that the amino glycosides also cause neuromuscular blockade. Right? The essentially work as nicotinic receptor blockers, the PDD activity of the nicotinic receptor. So since they have like an ability neuromuscular blockade, to hand over these drugs to people that have neuromuscular diseases. Right? So both have ALS, for example, or people that have my stench, for example. Right? Or people that have like polyodermatolymideocides, or people that have like lambrin, eti and myesthenic syndrome, giving those people a amino glycosides is not a smart idea at all. Right? So a amino glycosides, again, they have that cluster of nephrotoxicity, but they also auto toxic. Now, I also want to draw your attention to vancomycin. Vancomycin is also nephrotoxic and auto toxic. Right? And don't forget, there are other drugs that have that symptom cluster of nephrotoxicity. Your lube diuretics, especially ethycrinic acid, is also nephrotoxic and auto toxic. And then the anti-cancer drugs is platen, is also nephrotoxic and auto toxic. Right?

So some of you may wonder, why is this cluster almost always seem to exist together that, oh, if a drug damages your hearing, it also could potentially damage your kidneys. The thing is, there are many transporters that we find in the kidneys, that we also find in the inner ear. Those transporters work almost identically to each other. Right? So if one drug can nuke your kidneys, you better believe that it could potentially nuke the person's ears. Right? Here's the slight variations, but they are very closely related. So most drugs that are auto toxic, to be honest, we feel, end up also being nephrotoxic. Now, what if they give you a question about a person that has HIV? Right? And, you know, the acidity for candy, they were just nearly diagnosed. The acidity for candy was like 50. And then they tell you that they were studied on highly active antiretroviral therapy. And then, they were also studied on appropriate, pre-filactic measures. And then weeks later, you notice that these people's potassium is really high. Well, what's going on there? Well, I'm really hoping you're saying, hey, divine, this person has problems with trimethoprims of methoxazone. Right? So why is this person's potassium really high because of trimethoprims of methoxazone? Well, don't forget, trimethoprims of methoxazone is, you know, it's a fully synthesis inhibitor, right? We use it to perphylaxis against toxoplasmosis when your CD4 count goes below 100.

And, pneumocystis-dravetsi when your CD4 count goes below 200. Right? Now, these drugs are fully synthesis inhibitors, right? So like, if you look at it, TMPSMX, trimethoprims of methoxazone, right? The so-for-methoxazone inhibits an enzyme called dihydroethorite synthetase, right? It basically competes with an agent called PABA for dihydroethorite synthetase, right? So, but once dihydroethorite synthetase binds it, it cannot work on PABA. It's almost like you're taking off the spot that should be taking off by PABA. PABA means paraminobenzoid acid, right? And then the trimethoprim part of TMPSMX inhibits dihydrofully reductase. So, you don't convert dihydrofully to tetrahhydrofully, right? Now, when you have tetrahhydrofully, when you don't have tetrahhydrofully, you're going to have a lot of major problems with synthesizing a DNA, right? And also going to have problems with like B12 and all that metabolism, right? Methionine and all those things, right? But that's not the point of this podcast, right? So, the thing is these drugs, right? TMPSMX works in this way, right? So, because it inhibits fully synthesis, it can actually cause a presence of one more suppression, right? But why do these people have hyperchilemia? Well, if you think back to the principal cell of the nephron, remember that the principal cell of the nephron has an inech channel, right? That inech channel is on the urine side, it's on the epical surface.

It brings in sodium and sodium is coming into the principal cell, right? You are literally depleting the extracellular environment of the principal cell of positive charges. So, you're going to build up a series of negative charges. That series of negative charges or those negative charges, right? Let me be grammatically correct here. Those negative charges that you're building up, right? It's going to start ripping potassium ions out of the principal cell. And that makes sense. Remember, potassium is primarily an intracellular ion. So, there is a ton of it inside the principal cell, okay? So, normally just by gradient energy, right? Because again, there's more potassium inside the cell than outside the cell. Potassium will flow down its gradient to the outside of a cell. But you essentially augmenting that potassium gradient by this build-up of negative charge on the outside. It's almost like you have creatine and electro-study gradient as well that will draw potassium out, right? So, that inech channel, as most sodium is reabsorbed, you create those negative charges and then you draw potassium from the cell, right? So, the thing is, try to open stuff from a thox as all. Actually works like a potassium-sparing diuretic. It blocks those inech channels. So, think about if you block those inech channels, then you never end up creating those or you unamot reduce magnitude. End up creating almost no negative charges in the extracellular environment of the principal cell.

So, that means you have all these positive charges there that are not supposed to be there. So, those positive charges, if you can imagine it, they would potentially repel a person. Because those potassium ions that are trying to come out of the cell, when they see all these positive charges, they almost like repel back. They're like, go back to where you came from. Don't come out here, right? So, they are repeled. So, those potassium ions that are not being excreted, right? With your urine, they're going to build up in your body. So, you're going to get hyperkalinear. Hyperkalinear is a time-honored side effect of trimethyprem, so-from-a-thoxesol. Now, the thing is, since I guess we're on the topic of trimethyprem, so-from-a-thoxesol, you can also give your question about a person that takes TMPSMX, right? And then they tell you that the person, you know, starts becoming fatigued, starts having shortness of breath. And then they show you that this person has an in the developed jaundice, and they have an indirect hyperbularibinemia. Well, what in the world happened there? Well, I hope you're seeing that, hmm, divine. The stuff that happened there is this person has G6 PD deficiency, right? G6 PD, right, is again, glucose-6 false-fidihydrogenase. Now, G6 PD, you know, is an excellent recessive disease, right? So, you shouldn't be showing up in ladies on the exams, right? It should be a male-only question-out. I hope you're kind of latch on to that.

But, you know, in addition to just showing up in guys, right? Remember, in G6 PD deficiency, glucose-6 false-fidihydrogenase doesn't work. So, you're going to have a lot of problems with degenerating any DPH. All right? You're going to have a lot of problems with degenerating any DPH. And, you know, you need any DPH to deal with reactive oxygen species in your body. So, when you're taking a drug, that's a patholoxidizing agent, right? Like this sulfur drugs. Remember sulfur? If you remember from, you know, general chemistry in college is in group six of the periodic table like oxygen. It's a very patholoxidizing agent. So, it can cause oxidative stress, right? So, that oxidative stress, if you're not able to make any DPH, you cannot do that growth-athion system properly, right? So, you're going to be kind of being troubled there, right? So, that's why sometimes before people have started, especially these African Americans, or people from like susceptible populations like Greek, Mediterranean populations, you don't, it's not always done, but a prudent physician should probably order. G6-PD assays in these people, right? So, remember, G6-PD deficiency, right? Because you cannot deal with oxidative stress, that damages the ribloxel. A ribloxel explodes, right? You're going to have a lot of himoluses, right? You're going to have indirect type of urbanemia. That's why the person has those findings.

And then, another thing I guess I would say is that, remember, these people that have G6-PD deficiency, right? They're going to have high-ends bodies on a blood smear, and they're also going to have bite cells, right? So, again, think of G6-PD deficiency being problematic when you eat things like phababines that are powerful oxidants, right? When you take things that are powerful oxidizing agents, like those are like nitrates, right? So, they can give you a person, you know, that is taking nitrates for something, right? Like nitrates, nitro-perside, right? Those drugs are very powerful oxidizing agents, right? You're just be careful of those things in people that have G6-PD deficiency. You have one primary coin, right? Primary coin. Many people that have populations that have G6-PD deficiency, and also have malaria in those populations, right? So, you can already be seeing, getting to see the MBM, it concoct this malaria question, present to primary coin, and then, boom, they have all these findings, right? Again, think of glucose 6-phosphate dehydrogenase deficiency, right? And again, people that have G6-PD deficiency, whether you like it or not, these people are susceptible to infections, right? Especially the infections that are cleared by neutrophils. Because the thing is, again, NEDPH is very necessary for, surprise surprise, NEDPH oxidize to work, right? So, if you have an NEDPH deficiency, you don't have enough co-enzyme for NEDPH oxidize to work, right?

So, your reactive oxygen burst is going to be okay, but it's not going to be as good, right? It's not going to be as good. So, notice I, you know, I didn't say, oh, how do I suppose it will work? But, again, if NEDPH oxidize doesn't work, it's just going to have problems, right? You're going to have problems. But the reason why this would have, like, overwhelming strings of infections, like people with chronic granuloma, those disease, is that even if glucose 6-phosphate dehydrogenase doesn't work to produce NEDPH, there are other enzymes in the body that can make NEDPH, right? Like, if I'm not mistaken, there is an enzyme known as MALIC enzyme. It's like, again, we're not going to go deep into biochemistry today, but I believe it's called the NEDPH-dependent MALIC enzyme. I think MALIC enzyme converts NEDPH-plus to NEDPH, right? So, that's like an alternate pathway that can help. So, since we've gone on for almost 23 minutes, I'm going to go ahead and pause here. Can I do offer one or one tutoring for all the USMEL exams? Step one, step 2 CK, step 3, pre-clean cool medical exams, 30-a-clature shelf exams. I also offer tutoring for the internal medicine of entering exam and the board exam. So, if you're interested in any of those things, just shoot me an email. I have worked with thousands of people in my life. Again, fast majority of the people have worked with have done extremely well on the exams. At least my podcasts should give you a good indication of how I teach.

And for those that are attending the webinar tonight, the webinar will give you a very good indication of what my courses look like. We're going to be going for just an hour in the webinar, right? But my courses are 24 hours long, my school is 75 hours long. So, you can imagine times 24 or times 75 of what you see today. Right? Now, give you again an idea of how well put together the courses are. And then I do have these podcasts, an Apple podcasts, on Google podcasts, on Spotify, at least the most recent 150. So, the 230 or so podcasts that you don't see there, again, it's a rule. It's nothing I can't really circumvent it. So, if you want everything from episode one, all the way to episode 380, just go on the website, divideintroventionpodcasts.com. If you subscribe to the website with your Word Press accounts, you'll actually get an email notification whenever I make a new podcast. And then I have a You Tube channel called Divine Intervention, USMD podcast and videos. That's where I post the videos that I make. And then, I also help with Eras applications. I know literally like the day the match ends, is the day the next era cycle starts in my book. I've already started working with people for the Eras applications for the 2022-2023 cycle. So, if you're interested in any of those things, shoot me an email and I'll give you some more information. So, thank you for listening to me today. Have a wonderful rest of your day. Have a wonderful weekend. God bless you.

I'll see you in episode 3 D1.

Oral acyclovir.

Only for patients with very severe illness or those who cannot tolerate oral intake.

Aminoglycosides (e.g., gentamicin).

$\text{Na}^+$ reabsorption creates a negative electrical gradient, drawing $\text{K}^+$ out of the principal cell and into the urine.

Glucose-6-phosphate dehydrogenase (G6 PD) deficiency.

Vancomycin primarily covers Gram-positive infections; Aminoglycosides cover Gram-negative infections.

It is a DNA polymerase inhibitor (specifically, it inhibits a DNA-dependent DNA polymerase). Be prepared for alternative terminology like "inhibitor of a DNA dependent DNA polymerase."

It is a folate synthesis inhibitor. The trimethoprim component inhibits dihydrofolate reductase, while sulfamethoxazole competes with PABA for dihydropteroate synthetase.

Hyperkalemia. Mechanism: $\text{Na}^+$ reabsorption creates a negative charge in the tubular lumen, which electrochemically draws positive potassium ions out of the principal cell into the urine.

Inhibitor of an RNA-dependent DNA polymerase. This reflects that reverse transcriptase uses RNA as a template to produce DNA.

Indirect hyperbilirubinemia and bite cells (schistocytes).

To prevent opportunistic infections, such as Pneumocystis jirovecii pneumonia (when CD4 count < 200) or toxoplasmosis (when CD4 count < 100).

It is a DNA polymerase inhibitor (specifically, it inhibits a DNA-dependent DNA polymerase). Be prepared for alternative terminology like "inhibitor of a DNA dependent DNA polymerase."

It is a folate synthesis inhibitor. The trimethoprim component inhibits dihydrofolate reductase, while sulfamethoxazole competes with PABA for dihydropteroate synthetase.

Hyperkalemia. Mechanism: $\text{Na}^+$ reabsorption creates a negative charge in the tubular lumen, which electrochemically draws positive potassium ions out of the principal cell into the urine.

Inhibitor of an RNA-dependent DNA polymerase. This reflects that reverse transcriptase uses RNA as a template to produce DNA.

Indirect hyperbilirubinemia and bite cells (schistocytes).

To prevent opportunistic infections, such as Pneumocystis jirovecii pneumonia (when CD4 count < 200) or toxoplasmosis (when CD4 count < 100).