DIP Episode 35 - Antifungals and Antiparasitics

Hi, hi, welcome. My name is divine. I am a PGY1, I guess a recent PGY1. And today's episode, this will be the 35th episode of the Divine Intervention Podcasts. And today we're going to finish up the antibiotics. I'm going to talk about the anti-fongals and the antiparasitic medications. They should be a relatively short podcast. So for the anti-fongals, right? So basically, fungi have cell walls and cell membranes. The cell walls, the amide of chitin and gluchen, and there's a big high-yielding enzyme you want to know that helps with making fungal cell walls. So again, not cell membrane, fungal cell walls. Okay, the cell wall enzyme you want to know is B2 D gluchen synthase, B2 D gluchen synthase. And then, if you want to make a fungal cell membrane, you need a cholesterol derivative known as egosterol. And there are many steps in this synthesis pathway, but there is probably only two that you need to know for exams. So what are those two? The first step you want to know about for exams is a person going from squelting to a monosterol. Testombanins, I'm known as squelinypoxidys. So squelinypoxidys acts on squeliny. And then, going from monosterol to egosterol with the enzyme 14-alpha demethylase. Okay, so monosterol to egosterol with 14-alpha demethylase. So if you created a drug that inhibited squelinypoxidys or 14-alpha demethylase, you could cure fungal infections. So first of all, let's talk about the cell wall inhibitors.

The first cell wall inhibitor I'll talk about are the drug last one as the kino-candins. So candins should already tell you that these drugs work well for candida. Okay, so the cell wall inhibitors, the kino-candins, the inhibitor that beta-d gluchen synthase enzyme that helps you making the cell wall. And basically, these drugs, the all-endent fungin, right? So like Caspo fungin, Micophongin, Anidola fungin, you basically use these all for invasive candida infections. So that's it with the cell wall inhibitors. For the cell membrane inhibitors, like I said, you want to inhibit squelinapoxidys. That was the first time I mentioned in going from squeline to lanosterol. And the drug that does this is terbina-fin. Terbina-fin classiclyon exams is for neo-fungus, right? So anico-micosis. And I'll just go ahead and say one thing. This is probably more relevant for step two, but maybe I'm going to use your step one question. But if a person has tiniacapitis, right? So like head fungus or neo-fungus, you never use topical stuff. Topical stuff will always be the wrong answer on exams. You always want to use the oral stuff like the systemic antifungals, usually like terbina-fin. Or you could also give like oral greasy ove. Now the second thing that my secubin inhibitor is a 14 alpha dimethylase. That's what's inhibited by these all. Okay, remember that's the enzyme again that converts lanosterol to agosterol. So the big hyodroges you want to know about here, there's ketoconazole.

Okay, ketoconazole. It's primary mechanism of action is like I said inhibits for thin alpha dimethylase. But there's some other hyodstock with ketoconazole, right? It also inhibits desmolyse. Okay, remember that's one of the enzymes that helps you convert cholesterol to many things in the synthesis of stuff in the adrenal glands. Okay, so like synthesizing androgens, mineralocorticoids, glucocorticoids. And also don't forget that this is the enzyme that's actually activated by ECTH as well. So this is why you can use ketoconazole to actually treat pushing syndrome, right? So an oversecretion of cortisol. If inhibited, there are big enzymes that helps with synthesis of all that fun stuff. Desmolyse. ketoconazole, right? Remember that crack amigos nomonic? We talked about in a prior podcast. So hopefully that helps you remember that ketoconazole is also a cytochrome P415 inhibitor. That's the key in crack amigos. And then it has antanrogen effects. The big thing I'll just say to remember here is that it inhibits multiple enzymes in the antigen synthesis pathway. So you can actually cause a gynecomastia and like decreased libido, for example. And actually there is a nomonic you'll learn about as you study for step one for the drugs that classically cause gynecomastia. And the nomonic is stacked like STACD. I'll let you think about why that nomonic mix ends. But the S stands for spiranylactone, okay? The T stands for THC, right? So like marijuana.

The A, I believe stands for alcohol. So if you use alcohol chronically, that can cause a high-press regionism because it impairs the functioning of your liver. So the person can get gynecomastia with that. The C's for cymedidine. Remember that's the H. The H is it one or two. Believe it's the H2 blocker that also has antanrogen effects. So you can cause gynecomastia. ketoconazole as I mentioned, estrogen obviously. And then the jocsin, okay? Remember that sodium potassium ETP is inhibitor. Hopefully I'll have some time to do cardio pharma series of podcasts. I'll talk about the jocsin. So other isols, right? This fluconazole, my conazole, this is acroconazole. This is the one that shows up quite often on exams, right? It's usually the right answer in terms of treatment of like dimorphic fungal infection like coxae or histoblastone, okay? But another high-yodon usual thing that maybe I know an unusual example question is you can actually use it. It's a conazole in HIV prophylaxis, especially in patients that live in susceptible areas, right? So you can use it to prophylax against coxae. For person, live for example in Nevada or California or West Texas, blah, blah, blah, blah. You can prophylaxis via cd 4 count is less than 250. But for his stone, for person, again, lives in a susceptible area like Kentucky, for example, you can prophylax against his stone at a cd 4 count less than 150 with it's a conazole.

So if your conazole cd 4 less than 250 susceptible area, cover coxae, cd 4 count less than 150, it's patient susceptible area histoblastosis, cover with it's your conazole. And then another isol is worried conazole. The only way I've seen this tested a common leon exams is in the context of aspergillus. So they can describe a person that has like a fungus ball in their lungs or a person that has a cgd, remember aspergillus is catalyst positive, so people cgd get recurrent infections with catalysts or positive organisms. Okay, where conazole is very good at covering aspergillus. And then the last set of anti-fungals, I'll talk about the things that just bind to a gastro and basically make holes in the fungal cell this is where we have like amphoteric, sorry, fungal cell membrane. So these are drugs like amphotericin B, aka amphoterable and nice statin, right? So amphotericin B. Basically, I've mentioned the mechanism of action. You essentially use this for any life threatening fungal infection. Like a person has like cryptococomininitis, classic H-patient, India-inxthane showing like the subbubble side. You can cover cryptocococomininitis with amphoterable and flu cytosine. Okay, although in this case you actually have to give it intraathically to the spinal cord because amphob actually cannot cross the blood brain barrier very well. And also, classically on exams, amphob is what you want to give for mucomicosis, right?

So, you can describe a diabetic patient with like facial infection and like headache or like sinus pain, think about mucomicosis, classically it's from rhizopause on exams. Now, amphoterable is a phenomenal drug. It cures most if not every fungal infection, but it is severely nephrotoxic. And there are certain things you could do to prevent this nephrotoxicity, right? You can hydrate the patient like cotton or you can actually give the liposomal formulation of amphoteric synb, it's actually relatively safe, at least better than the straight up amphoterable. And then my statin, my statin has the same mechanism of action. Classicly on exams is used to treat oral candidysis. Okay, you can use it as a swish in swallow. It's not reabsorbed in the GI tract, so not a huge issue. If a non-mustache can actually, my statin is actually a little more toxic than amphoteric synb, but it's not reabsorbed, so it doesn't cause much of an issue. And actually, I like when I said it would be talking about the last fungal drug class, there's probably like two more I need to talk about, although it's very little, there's flu cytosine, okay? So if you go back to your cell bulge here, right? The difference between cytosine and uracil is an amino group. Uracil does not have an amino group, cytosine does have an amino group. So if you remove the amino group from cytosine, boom, you'll form your cell. So it so happens that five flu cytosine is a fungal drug.

And actually, the way it works is that cytosine diamines will convert the five flu cytosine to five fluoride uracil. So basically, you're making an anti-cancer drug in the body. And then that five f-u-inhibit thyme deletes in this. And that is actually how five flu cytosine works as an anti-fungal. And again, because it's an anti-cancer drug, basically, it can suppress the bone marrow. So that's one classic side effect. But the big thing you want to remember of five flu cytosine is you can use it to treat crypto-cocomanian gytus. And then the last fungal drug is a greasy ofulvin, right? So greasy ofulvin basically works like the vinka alkaloid, right? To remember, your vinka alkaloids prevent polymerization of microtubules. Although the mechanism of ultrasound or greasy ofulvin is a little shaky, but just sort of take that for your exam. Sort of works like vinka alkaloids prevent polymerization of microtubules. Remember, this is also how cochisin works. Cochisin also works by preventing microtubule polymerization. And don't forget to remember the nomonic, gynus, coronas, and PB Rs induce chronic alcoholism. Greasy ofulvin is actually an activator of cytochrome P450. So that's just one of those things. It's an inducer. So you want to go ahead and keep that in mind. And then, so it's a microtubule it's very good at accumulating tissues that are reaching character. So that's why we use it to treat like demodophyte infections.

And you want to know your classic bugs that cause demodophyte infections, like all your tiniest, right? There's three of them that we classically text on exams. There's micro sporum. There is tricofighting. And there is epidermal fighting. Okay, so like micro sporum, epidermal fighting, and tricofighting. Okay, so now let's talk about the antiparasetics. I'll probably spend like two minutes on this. These drugs I am not going to discuss the mechanism of action because it offers probably like zero yield on exams. So you just need to know bug drug that covers it. So I'll just run through this real quick. This is very good flashcard material. So the first drug I'll talk about is primary queen. Remember it's used to treat plus modium infections, right? Especially P5 X and PO Valley. Remember those have like hypnosoid stitches that can lead to the liver and cause a malaria reactivation. So you can cover that hypnosoid face with primary queen. You'll probably want to avoid primary queen in a patient with a G6 pd deficiency because primary queen is actually a patholoxidizing agent. So you can mess with that growth of thion system. Now the next drugs I'll talk about there's chloroquine, atovacone progoneal, at the methyl lumephantrine. So again chloroquine, atovacone progoneal, at the methyl lumephantrine, you can use these to treat malaria.

Don't forget that atovacone plus clindamycin is actually one potential option for prophylaxis in a patient that has a neuromus, that has HIV against a pneumocystis-jurveti when the cd 4 counter goes below 200. Next drug, sodium stable glucone to use these to treat leshmaniasis. So sodium stable glucone slashtomaniasis, nifordemox and benzenezo. You can actually use those to cover tripanosomal cruzii. Remember tea cruzii causes big everything. It can cause ecalegia, so biggest of us. It can cause a dilithic cardiomyopathy, so big heart. It can cause a big GI tripe because it can cause phrasprone disease. It can destroy your albax and mysensplexi. And then the next drugs are suramine and melastopro. These actually cover tripanosomal cruzii. That's the African sleeping sickness. Those can be covered with suramine and melastopro. And then prezyquantil and your bendazol. You can actually use that to treat it like a lot of type warm infections, a lot of fluke infections. So your bendazol, albendazol, fire bendazol, mebendazol, blah blah blah. Selenium sulfite. The big thing one of the memories that it covers malacisia ferifer. Remember the spaghetti and meatballs appearance on microscopy? Lindein was actually previously used to treat scabies. But on exams, this will always be the wrong answer because it's neurotoxic because it's like seizure. So you don't use it anymore. The patient has scabies.

So usually you'll say fingerwebs has all these nasty stuff, very itchy person, usually a person like pretty bad hygiene, quiet and give permethrine. Topic opemethrine is the drug of choice on exams for treating scabies, not lindding, lindding, causes or seizures. Now the next drugs I'll talk about are paromomysin and nitazoxanide. So paromomysin and nitazoxanide. Those cover cryptosporidium parvone. Okay. So think about a HIV patient that has watery diarrhea and they say, oh you do, you do a stool whatever and you find acid fast osis in the stool. If you find that thing about a sea parvone, cryptosporidium, not cryptococcus, cryptosporidium, you cover that with a nitazoxanide and paromomysin. Although don't forgive a nitazoxanide can actually also cover intamibahistolyrica. Although you can use metronidazol for that as we remember the get gap on the metronidazol in get gap stands for intamibahistolyrica. Remember that's like the highoportosol infection that presents as a bloodied area and can also present with liver lesions. Now, Ivermectin. The big thing to remember here is that it covers strongeloidis, stercoralis and you can also use it for uncle checkovolvulus. So Ivermectin and then just strongeloidis and uncle checkis. Those can be covered with Ivermectin. And then paliviziumabribevaryn already talked about this paliviziumab use it to cover RSV ribavaryn, remember it inhibits RNA polymerase and also inhibits aninosimmonophosphid dehydrogenase.

Okay, so you can use that for hep C, you can use that for RSV as well. And then one other like weird antibiotic I just never mentioned is phedaxomycin. You can use it as a like a basic like a third life for C-DeF. You do for C-DeF, you try metro first metronidoso. That doesn't work. You can consider oral vancomycin, not IV, oral vancomycin. And then if that doesn't work, you could consider phedaxomycin. That doesn't work. Then you're probably looking at a fickle transplant. Okay, so you basically transplant poop. So thank you for walking along with me with this journey through antibiotics. So we're done with the antibacterials, the antifongals, the antipyraesthetics, and the antivirus. If you know this information, it should be good to go on micro from ecology for any body exam. So I wish you all the best. If you ever have any questions, feel free to drop me and I will see you in the next podcast. Thank you and God bless.

$\beta$-D-glucan synthase, which synthesizes fungal cell walls.

Azoles (e.g., Ketoconazole, Fluconazole, Voriconazole).

Aspergillus species infections.

Topical application will always be incorrect on exams; systemic/oral antifungals (like Terbinafine) are required for deep fungal infections.

Binding to ergosterol and forming pores in the fungal cell membrane.

Griseofulvin.

Cushing's syndrome (oversecretion of cortisol).

Echinocandins (e.g., Micafungin, Caspofungin).

Both bind to ergosterol, but Nystatin is typically used topically/orally for candidiasis, while Amphotericin B is reserved for severe systemic infections.

Fluconazole and Voriconazole.

Microsporum, Trichophyton, and Epidermophyton.

Primaquine.

Nitazoxanide and Paromomycin.

Microsporum, Trichophyton, and Epidermophyton.

Echinocandins (e.g., Micafungin, Caspofungin).

Both bind to ergosterol, but Nystatin is typically used topically/orally for candidiasis, while Amphotericin B is reserved for severe systemic infections.

Fluconazole and Voriconazole.

Microsporum, Trichophyton, and Epidermophyton.

Primaquine.

Nitazoxanide and Paromomycin.

Microsporum, Trichophyton, and Epidermophyton.