DIP Ep 674: USMLE Pharm Crash Course, The Drugs That Matter (Part 5)

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This episode is part five of a pharmacology crash course series specifically designed for USMLE Step 1, 2, and 3 candidates. The host review

Key takeaways

• Isoniazid inhibits mycolic acid synthesis and can cause peripheral neuropathy by inducing a functional Vitamin B6 deficiency.
• Rifampin is a potent cytochrome P450 inducer that can accelerate the metabolism of drugs like warfarin and oral contraceptives.

Main topics

• Tuberculosis pharmacology
• Antifungal mechanisms and toxicity

Notable quotes

Clozapine is the most effective antipsychotic.

Conclusion

The episode serves as a high-yield review of critical drug classes for

Transcript preview

Speaker 1 (0:00) All right, welcome. My name is Devine. Let's pick up back where we left off. So this stretch, we're going to be hitting the... you know, some more drugs. Again, I say that this is like a farm crash course. And honestly, like this course, I think will be really helpful for people, you know, studying for step one, for step two, CK for step three. Again, it's going to be a six part series of the most important drugs that tend to pop up on the USMLE exams. I remember there's a class I was teaching yesterday. People were like, hey, Devine, like, how do I study pharmacology for step three? Well, this six part series is a great place to start. It's a great, great, great place. to start. And if you like the way I teach and you like the way I integrate information, you're going to love my classes. I have a series of classes taking place in the month of October. So I have a test-taking strategies class that's two and a half hours long. I have a biostatistics class that's four hours long. I have a social sciences, quality improvement, hospital medicine or ethics class that is five hours long. those classes are all for step one all the way to step three. There's tons of people that have taken those classes and they have found that to be really helpful because, again, the classes are not lectures. They're reviews, right, that are done by way of questions. So I review the content. I review test-taking principles by using questions. And I make a lot of integrations. I use a lot of cases, right? So it's like you're learning problem-solving while you're taking these classes. And then for step two and step three specifically, I have a 20-hour review. That's a 5D class, four hours a day. And then I have a last minute review that's three hours long. And also for step one, I have a 25-hour step one review. That's taking place in the first week of November. And again, all these classes over Zoom, they are completely thought by me. So again, I think many people have taken these classes, found them to be really helpful. I've had like I literally got an email from a person that took my step two class recently and they got a 260 on their exam. They literally took the class within the past month. Right. So these classes are well validated. People do really well after taking these these classes. All right. So let's and if you want to sign up, just click in the link below or shoot me an email through the website or something like that. All right. So again, picking up back off where we where we left off. Right. So. Speaker 1 (2:21) Again, I'm going to hit some drugs that are really important here. And again, I'm telling you this, understanding not just presentation, but understanding mechanisms, understanding side effects will really go a long way for you. Really, really go a long way for you with this stuff, right? So just kind of keep that in mind, right? So what if they give you a question about a person, right? And the person is being treated for TB, right? The person is being treated for TB. And then they tell you that this person... you know, starts having like a pins and needles sensation in their extremities and things of that nature. If you see that, what should you be thinking about? Well, I'd really hope you're thinking about isoniazid toxicity, right? So remember, isoniazid is one of these drugs that is used for TB, right? It works. How exactly does it work? Well, basically, it inhibits mycolic acid synthesis, right? In the mycobacterial, you know, cell wall, right? So... That's why isoniazid, we really don't use it for anything that is not mycobacterial because it is very specific for mycobacterial species, right? And one thing that you should know about isoniazid is that the way that it gets metabolized in the body is by a process known as acetylation, right? Acetylation. And obviously that's going to take place in the liver. Right. So the thing is, patients that are slow acetylators, they build up very high levels of the drug and they are very prone to toxicity. This is one of those things I'm sure you probably last saw studying for, you know, some exam or early med school. And you think that they'd never tested on the USMLEs until you see that your mouth kind of drops, drops wide open. Right. So I'd keep that in mind for your exams. Right. And. The thing is, the reason people get peripheral neuropathy with isoniazid is not because of isoniazid itself. It's just that isoniazid depletes your vitamin B6. It causes a functional vitamin B6 deficiency. How does it do that? Well, the thing is, remember, another name for vitamin B6 is pyridoxal phosphate. Well, the thing is, for... So pyridoxine to be made into pyridoxal phosphate, it needs activation by an enzyme. That enzyme is known as pyridoxine 5'-phosphokinase, right? So isoniazid is a very potent inhibitor of that enzyme. So if you inhibit that enzyme, you will literally not make the active form of vitamin B6. So you're going to have a functional B6 deficiency, right? Functional B6 deficiency, right? So that's why you're told whenever you're taking isoniazid that you take B6 at the same time. You take B6 at the same time, right? So anybody studying isoniazid, especially people that are like diabetics, people that are alcoholics, you know, people that are prone to B6 deficiency, diabetics, alcoholics, people that are pregnant, people that are malnourished, they're told that, hey, make sure you're taking B6. If not, that neuropathy is going to come quick and it's going to come fast, right? And again, remember what I said, isoniazid is literally activated by the liver, right? Acetylation. So it just kind of tells you, it kind of makes sense that this drug may also be hepatotoxic. right? And the hepatotoxicity is dose-independent. It is dose-independent. It doesn't depend on the dose. You can have hepatotoxicity pretty much at any dose, right? So again, you can have LFT abnormalities in a person that is taking isoniazid, right? And I guess since we're talking about TB, let's kind of delve into rifampin, right? So remember rifampin, you definitely want to make sure you know the mechanism of action, right? It inhibits DNA-dependent RNA polymerase. Guys, let me tell you something. Whenever you're learning these drugs that work at the genetic level, I will encourage you to not just know the simplistic mechanism of action like, hey, inhibits RNA polymerase. No. The thing is, our friends at the NBMEs, they have this weird thing they want you to know. Like, hey, is it DNA dependent or is it RNA dependent? So it inhibits the DNA dependent RNA polymerase. So that