DIP Episode 71 - Oncology Pharm Part 2 (Final Part/Cell Biology Episode)

Okay, welcome. My name is Devine. I am a PGY1 resident going into ideology. Into this podcast we're going to finish up on Chromacology. I'll just go ahead and see this right of the bad that this particular podcast is super, super high yield because I'm not just going to be talking about the drugs. When I'm going to be talking about a lot of cell biology, cell biology correlates that you love to test in this context. So I'll encourage you to sort of pay attention to this one. And I'll try to work through the material relatively quickly so this is not too long. But trust me, there's a lot of high yield drugs I'm going to talk about today. So yesterday we stopped at BLU. My center member I said it's the only G2 specific agent. And then today we're going to the next drug class known as the Alkalytine agents, right? So the Alkalytine agents. Now, the thing is these Alkalytine agents, the key thing you want to remember is that they crosslink DNA. Okay? They crosslink DNA. The thing is I talked about how you want to recycle and for example cause intercollation of DNA web, they basically stand in the way of DNA forming bonds. The thing is in the case of these Alkalytine agents, by virtue of their mechanism of action which I'll discuss shortly, because cross-linking cross-linking happens where you basically, by certain chemical modifications you make to DNA, you make you begin to form like weird bonds, right? So normally like guanine binds with cytosine.

But if for example you methylated the DNA, right? Because remember, methyl is an Alkalytine agent. And then you begin to cause bonds to form between like guanine and thymedine, like a GT bond. And that's not ideal, right? That's what's known as cross-linking. Okay? That's how you differentiate cross-linking from intercollation. Intercollation is like, oh, G and C want to form a bond, where you sort of like stand as a mid-o-man and prevent them from bonding. And then cross-linking is you chemically modify DNA so that you begin to have weird bond formation. Okay? That's how you differentiate those two. It's actually very high yield to know those key differences. So the mechanism of action of these Alkalytine agents, right? So basically the key thing you want to understand here is that guanine has nitrogen on the seventh position. So it's called the N7. When you add a methyl group to this N7 position again, you can begin to make guanine's transform very strange bonds like GT base pairs. Now, the thing is these drugs in addition to methylated N7, these Alkalytine agents, there's actually some Alkalytine agents that also add Alkyl groups to the O6 position. Those are specifically the nitrosoerias because as you learn, the platinum agents are all Alkalytine agents, the cyclophosphamide, phosphamide are both Alkalytine agents, but these generally do not add methyl groups to the O6, right? All they do is like N7 methylation. I mean, N7 Alkalytine, then be more specific.

But if you want N7 Alkalytine and O6 Alkalytine, think about your nitrosoerias. I'll talk about those in a bit. So let's talk about the first group of Alkalytine agents. We have a cyclophosphamide and I-phosphamide. Again, the cross-ling DNA, the thing is they need to be converted to active metabolites by the liver, so by like the cytochrome P450 system. So the thing is if you give a CIPP-P415 inhibitor or the person has liver dysfunction, these drugs will basically not work. And the big, big side effect you want to remember with these drugs is that they cause hemorrhagic cystitis. Please don't forget, right? If they give you a question about a person that's from Egypt, that's swam in the Nile and then has hemorrhagic cystitis, hopefully you're thinking about she's to somahematobia. If you see a person that has like pink eye and they have like firing gytis, and they also have like maybe abdominal pain because this buck and caused diarrhea, and they also have hemorrhagic cystitis. I really hope you're thinking about firing go conjunctivitis associated with adenovirus. Adenovirus can also cause hemorrhagic cystitis. And the thing is the hemorrhagic cystitis that's associated with cyclophosphamide and Iphosphamide. And it actually comes from metabolites that's known as acroline. Acroline is a metabolite of cyclophosphamide, Iphosphamide, it is basically a vesicant, right? So if you see the word vesicle, it usually means bladder.

So a vesicant is something that like basically nooksia bladder. So the thing is you can try to prevent like ferradicol damage to the bladder by binding of that acroline metabolite with a drug known as mesna, okay? Very high to know that. Alternatively, you can actually give like very vigorous diuresis, right? So you give the person a crap ton of fluid and then give them leisics to basically just continuously wash through the bladder. In fact, some surgeons actually go with, I mean some oncologists go with like irrigation, like direct irrigation of the bladder. One other thing that maybe an usual animation you examine is the use of this drug in acetyl-sistine. In acetyl-sistine could potentially be used as well for hemorrhagic cystitis. Now, what do we use cyclophosphamide for? We use it for cancers, we use it for nephrodite nephrodite syndrome, and don't forget that cyclophosphamide is a pseudo-SID, right? So if they give you a person, question about a person that has been taking a cancer drug and then they have a low serimosponuality and a higher in osponuality, right? Or you can basically say like a uvolymic hyponitremia, right? So like a uvolymic hyposmolar hyponitremia, think about cyclophosphamide. And then the platinum analogues, again, same mechanism of acetyl-sistine DNA, the N7 position. The big drugs you want to remember here are drugs like cisplatin, cable platin and oxali platin.

These drugs are super nephrodoxic and the thing is the metabolite of these drugs that's nephrodoxic is something known as Amyphostin, so M-A-M-I-F-O-S-T-I-N-E. So these drugs are super nephrodoxic, oops sorry, made a mistake there. So the thing is the drugs, they are super nephrodoxic, they are metabolites that are toxic to the kidneys. You don't need to know exactly what those are, but the thing I want to mention is that you can prevent that kidney toxicity by giving a drug known as Amyphostin. Amyphostin binds up those metabolites so that they don't destroy your kidneys. Now these drugs in addition to being nephrodoxic, they are also auto-toxic. In fact, I will go ahead and say this, there are certain drugs that are both that are super nephrodoxic and for the most part are also auto-toxic. Those are drugs like vancomycin, so they share those two like side effects together. In addition to your platinum analogues, vancomycin has that property. Ethocrinic acid, remember it's a lube diuretic, remember your loops work at the thickest end of the lube of Henley to inhibit that sodium potassium, two chloride transporters. Ethocrinic acid, remember it's the only lube without sulfur allergy. It also is nephrod and auto-toxic. And then you have amino glycosides, right? Your 30th inhibitors, they basically kill initiation in ribosomes like gentamysine, your mesin, amicacin, and tobramysine and striptomysine. These drugs are also nephrod and auto-toxic.

In fact, you can use them to treat manoeuvres disease because you can have blood criniol nerve-8 with those drugs. Now, one big thing you want to know about these platinum agencies that the associated with really bad chemo-associated MSS, right? So a lot of nausea and vomiting. And the reason is that they actually agonists at serotonin receptors. So your platinum analogues very high, your platinum analogues agonists at serotonin receptors, right? And again, if you think about it, right, this drug that you've probably heard of in the hospital, Zofran, on Dancer Tron. On Dancer Tron is a serotonin receptor antagonist that blocks those serotonin receptors in the chemo-receptor trigger zone. And you're used to treat chemo-treatop, I guess, prevent chemo-induced amnesia and MSS. In fact, if you read the literature on Dancer Tron was actually discovered from people discovering the serotonin receptor agonist activity of the platinum analogues. Other things you can use to treat chemo-induced nausea and MSS, you can use metoclopromide, right? Meloclopromide will block those adopementate receptors that you can find again in that area post-traumatic chemo-receptor trigger zone. But also remember that metoclopromide being a dopamine antagonist, it can cause extraperamidol side effects like tardy dyskinesia. And don't forget that metoclopromide, right? It can also be used to actually treat diabetic gastroperaces.

Because if you remember from the side and neuro-podcasts, I said that whenever a chemical equation is that you should establish in your mind is that there's an inverse relationship between your levels of dopamine and your levels of acetylcholine. If you block dopamine receptors, your levels of acetylcholine will go up. If your levels of acetylcholine go up, you will have, remember, parasympathetic risk and digest, you have more flux through your GI tract and you can potentially treat gastroperaces. Remember that I read through my sin, which is a multiline receptor agonist, can also be used to treat diabetic gastroperaces. And then one of the drug you can use to treat a chemotherapy induced an nausea and MSS is a drug known as a prepetent. So the thing is there are neuro-kindin-one receptors, again, in the chemo-receptor trigger zone ear-oppostreama, so you can block those NK-1 receptors by giving a prepetent. And that should also again prevent or treat chemotherapy induced an nausea and MSS. And then the next group of alkalinity agents are the scosa, the nitrosoureus. Again, the cross-ling DNA, so the alkalinity, the N7 and O6 positions, so like N7, O6 on a 1. And the big drugs you want to know here, they are drugs like carmoustine, semoustine, they all end in moustine. Although there's a weird one, streptozosen, streptozosen, actually there are two weird ones. The first one out, weird one I'll talk about is streptozosen, is a nitrosourea.

It's actually used very specifically on exams to treat insulinomers. So if you ever see an insulinoma question, remember weeple striad, where people have like hypo glycemia and signs of hypo glycemia, and then the symptoms get better with the administration of glucose, especially in the context of the MEN-1 syndrome, has a pancreatic neuroendocrine tumor, considering giving those people streptozosen. But the thing is for the most part, your nitrosourea is the atnims end in moustine, right? I mean you've probably heard of the mnemonic that should put some nitro in your moustine. So again, streptozosen primarily for insulinomers, these drugs they are very good for brain cancers like glioblastoma multi-forming because they can cross the blood-brain barrier. In fact, I will tell you this, the current standard of care for the treatment of, for the treatment of, of GBM, so glioblastoma, is using these nitrosoureas. In fact, I will say for the most part, people tend to use a drug known as timozolamide. Timozolamide is actually an alkalinity agent. But here is where, again, this is not in first aid yet, but is just one of these cell biology principles that has sort of come out in recent years, and I can almost predict that it will make its way to the USM Ls in a few years. And that's the concept of something known as an MGMT enzyme.

So the thing is, the MGMT enzyme is an enzyme that is actually naturally expressed in many cells, and the thing is, if you have a methylation error, it can actually fix that methylation error, right? So the thing is, if you are an alkalinity agent and your job is to calculate, like, methyligene, for example, and basically, from cross-links, if you are expressing that MGMT enzyme, that's not great for that drug, because that MGMT enzyme will basically undo the effects of the cancer drug. So the thing is, there are actually certain cancers that have an MGMT mutation, where like MGMT is like epigenetically silenced, when MGMT silenced, then you cannot undo the effects of alkalinity in agents like timozolamide. So in fact, I'll tell you this, many people that are being trained for GBM, they also get like some kind of testing for the MGMT mutation. If they have the MGM, if their cancer, if their tumor cells have that MGMT mutation, those people will have better effect from getting an alkalinity agent like timozolamide. But people that don't have that MGMT mutation, you probably don't want to give them timozolamide because it doesn't really work in that population. Now, the next alkalinity agent I'll talk about is Biosophane, cross-links DNA, big thing you want to remember again is that it can cause a pulmonary fibrosis like Bliomisin. I'll do remember Bliomisin is the G2-specific agent, right?

And then another alkalinity agent, I guess probably the last one I'll talk about is Procarbazine. Procarbazine is an alkalinity agent, but it also has like an off-pargadability to inhibit monoaminoxidates, right? So if you were to take Procarbazine with another serotonergic agent, that can potentially increase the presence risk of a serotonin syndrome. I mean, if they wanted to be evil to you on the US ML, they can say, oh, a patient is being treated with chemotherapy, right? So like they are being treated with Procarbazine. And then because of that, they have an immunodeficiency and then they have like a region like MRSA infection. And then you give those people a lenezolate and then boom, they can get serotonin syndrome from that. Because remember, Procarbazine is an MAOI in addition to being an alkalinity agent, but lenezolate in addition to being a 50s inhibitor of initiation is also an MAOI. So those two things, if you give them together, can trigger serotonin syndrome. That'll be a very clever step one question. Now, I guess going to the next group of oncology drugs, we have the topoisomerase inhibitors. Basically, remember, the way topoisomerase works is it relieves super coils. The way it relieves those super coils is that it causes DNA strand breaks, does some wiggling around, and then makes those DNA strands come back together.

Well, the thing is, these topoisomerase inhibitors, the way they work is that they wait for topoisomerase to have caused those DNA strand breaks. And then after you get the DNA strand breaks, those drugs inhibit the topoisomerase. Before, topoisomerase has the chance to sort of bring reactions together to join those strands back. So if you inhibit the topoisomerase at that point, you still have DNA strand breaks. If you have DNA strand breaks, that can trigger the poptosis of those cells. So that's how your topoisomerase inhibitors work as anti-cancer agents. And the thing is, there are two classes of topoisomerase inhibitors. They are topo-one inhibitors, right? So like topoisomerase one inhibitors. And these are drugs like Irino-Tican and Topo-Tican. You may say, oh, divine, how do I remember this? Remember, the I in Irino, for like the looks like a one, okay? So just remember it has one Irino-Tican, eating inhibits topo-one. So Irino-Tican, Topo-Tican, those are topo-one inhibitors. The topo-two inhibitors, they are called topo-two because remember, topoisomerase two causes two breaks in DNA versus topoisomerase one that causes one break in DNA. So your topo-two inhibitors include drugs like atoposite and teniposite. And again, you may say, divine, how do I remember these ones? Remember, the topo-side has E2-po-side. Okay? That will help you remember that inhibits topo-two. Okay?

And if you're going into antibiotic therapy, I don't forget that you're fluoroclinolones that can cause a cartilage damage, right? They also inhibit bacterial topoisomerase. In fact, bacterial topoisomerase occasionally is known as DNA gyries. Okay? You're fluoroclinolones are DNA gyries inhibitors. Now, next row class, we're going to have the micro-tubial inhibitors, your micro-tubial inhibitors. So the thing is, micro-tubules are like super important, right? You'll find them in like Celia, in Flajella, you'll find them in neurons, right? So it should make sense that if you're a micro-tubial inhibitor, you're probably not very good for neurons, right? There's a lot of neurotoxicity for the most part peripheral neuropathy with taking these micro-tubial inhibitors. And don't forget, right, from a cell biology standpoint, that your micro-tubules have a 9 plus 2 arrangement. Okay? And remember that you need alpha and beta tubulin to ultimately help you form those micro-tubules. So there are two classes of micro-tubulin inhibitors, right? You can basically have drugs that can bind to tubulin so that you never have the ability to form a micro-tubial polymer. So you can effectively say that these drugs are preventing the polymerization of micro-tubules. This is where your vincadrugs come from, right? So drugs like vinplastin and vincristin, okay?

These drugs by basically preventing the formation of micro-tubules, preventing the polymerization of micro-tubules, if you may, essentially prevent metapheys from happening because you need to build micro-tubules for metapheys to happen, okay? So again, these drugs are neurotoxic because peripheral neuropathy because they prevent micro-tubule polymerization. And remember that that anterior grade, retrograde transport business from the cell sum in a neuron to like the to the synapse all depends on micro-tubules, right? So this is why these drugs are neurotoxic. So let me just tell you this right off the bat. If you ever see a question about peripheral neuropathy in the context of a cancer drug on an NBME, always listen to me right now. Always speak of vincristin as your answer. Always, always, always 100% pig vincristin as your answer, okay? And also don't forget that the drug, one of these drugs that used to treat a pericarditis and also used to treat gut in some cases, cotisin, also works by preventing micro-tubule polymerization. Now, your next class of micro-tubule inhibitors are drugs that prevent depolymerization of micro-tubules. So basically these drugs, they essentially, um, they essentially binds to micro-tubule polymers and prevent them from depolymerizing. So if you're thinking about this again from a cell biology standpoint, these drugs will prevent anapheys from happening because the thing is you need to break down that metaphase business for anapheys to happen.

But if you hyperstabilize those micro-tubules and they never depolymerize, depolymerize, then you'll never have anapheys happening. That's how this second class of micro-tubule inhibitors work and these are your toxins, right? So drugs like a pachletaxel and dosetaxel. Again, these drugs have peripheral neuropathy as a side effect, but I'm telling you, like if you do an NBME exam, you should always go with vincristin if that option is presented to you. So you may say, ah, divine. How do I remember that vinca alkaloids prevent micro-tubule polymerization and your toxins prevent micro-tubule depolymerization? Here's one thing that has always worked for me. Just remember one and then you will remember the, and then you take the opposite for the other. And to remember one, I even have a nomonic for that. I just remember a VP like vice president. So the V is for the vinca alkaloids and the P is for preventing polymerization of micro-tubule. So that's the nomonic that may help you there. Okay, now the next anti-cancery general talk about is atra. So all trans-retinuic acid, this is mostly used to treat your acute pro myocytic leukemia, right? Remember, your acute pro myocytic leukemia, it's a kind of acute leukemia, right? And it's associated with that fancish-mancy 15-17 translocation, right? Remember that you see our rods on an exam. If they were to present this kind of cancer to you, remember those our rods, they can trigger DIC, right?

So the thing is if you have that 15-17 translocation, you have a lot of buildup of pro myocytes and pro myocytes still have the property of cell division, right? And the thing is if you have a cell that can divide, that's not good for cancer, because cancer cells, what do they love doing with their lives? They love to divide. So the thing is if you can give an agent that will cause these pro myocytes to differentiate terminally to myocytes, you basically cause them to differentiate to a cell type that has no further ability to divide. That's where all trans-retinuic acid comes in atra is basically like think of it as a transcription factor assistant, okay? It basically makes those cells differentiate down to myocytes and then once they become myocytes, they cannot divide any further, and boom, you've basically stopped the cancer from growing, okay? So that's how all trans-retinuic acid works. Now the next drug I'll talk about here is a drug known as Bortezomib, Bortezomib. This is a very high yield drug that's beginning to make its way to the USML is Y, because you can actually use it to treat a multiple myeloma. So let's talk about the mechanism of action of Bortezomib, but before we do that we need to take a small detour into cell biology territory. Now what's this small detour? The thing is there's a transcription factor that actually promotes the proliferation of certain cancers. This transcription factor is known as NFKAPB, okay? So that's the first fact.

NFKAPB is a transcription factor that promotes the proliferation of certain cancers, like multiple myeloma for example. Now the thing is there is an enzyme known IKAPB that has the ability to inhibit this NFKAPB, which is clearly a good thing, right? If you have a ton of IKAPB, you'll inhibit NFKAPB, and then you don't promote the proliferation of cancers. So the thing is the problem is IKAPB is broken down by proteisms in the cell, okay? So think about it, if your proteisms are just working like a lot like all your overexpressing proteisms for some bizarre reason, you'll keep breaking down IKAPB, you'll never inhibit NFKAPB, and the cancer will proliferate. So for these cancers that operate proteisms, again, the heap breaking down IKAPB, and you don't have that inhibition. So the thing is the proteism has many subunits, one of them is a 20 S subunit. The thing is Bortezza may have the ability to inhibit the 20 S proteism subunit, right? And if you inhibit the proteism, right? You basically prevent the breakdown of IKAPB, if you prevent the breakdown of IKAPB, IKAPB will persist for longer periods in the cell, and then you'll then have the ability to inhibit NFKAPB, and you'll basically stop that cell proliferation. So that's how Bortezza may works as a treatment for multiple myeloma. Another treatment you may see on examples is Thalidomide.

Thalidomide, that thing that causes fochomilia, is also used for multiple myeloma, but they say, oh, divine, why would you give Thalidomide to a person that has multiple myeloma? Well, the thing is multiple myeloma is primarily a disease that occurs in old people, right? Old people are not necessarily trying to have kids, people like in their 70s, for example, right? So giving them Thalidomide, you're not really concerned about that, if you're sort of comparing the risk reward, the reward is better because you're also treating the treating the multiple myeloma. Now, the next drug I'll talk about is a matnip, right? So let me just go ahead and establish a principle for you right now. Any drug that ends in Nib, okay, is a tyrosine kinase inhibitor. Just settle that for you right now. If you ever see a drug and it ends in Nib, like a matnip, the satinib, or a lotnip, whatever, it's a tyrosine kinase inhibitor. So a matnip is a tyrosine kinase inhibitor, but it's used to treat CML, right? So CML, remember, that's again, fancy disease, phyladofiocromozome, 922 translocation, right? You found this BCR-Ebol tyrosine kinase. And because that tyrosine kinase is considerably active, you have like abrand proliferation of cells. So you can use a matnip to inhibit that BCR-Ebol tyrosine kinase and you're good to go. Now, because they never want to memorize the matnip for CML, they also begin to introduce a matnip on USML as a treatment for GI stromal tumors, right? So like gist tumors.

The thing is gist tumors express a tyrosine kinase that's known as C-Kept. It's very high to another for exams. So that C-Kept's tyrosine kinase, you can also inhibit it with a matnip. Now, the next drug class I'll talk about, I'll talk about both together. That's a lotnip and cytoxymab. A lotnip is tyrosine kinase inhibitor, right? Cytoxymab is a monoclonal antibody against the receptor. I'm going to talk about right now actually. So the thing is, there are a few lung cancers that express like abnormal EGFR genes. Okay? They express abnormal EGFR genes. If you want to be super specific, that's like the herb B1 receptor. Okay? The herb B1 receptor. Please don't confuse the herb B1 receptor with the herb B2 receptor. The herb B2 receptor is the thing that is also known as the HER2 new receptor in a certain breast cancer that is targeted by Cytoxymab, which I'll talk about in a bit. But EGFR gene ultimately helps you express the herb B1. Okay? And the thing is herb B1, right? It's a tyrosine kinase receptor. And one high yield cell biology correlate here is that herb B1 actually works through K-RAS as a second messenger system. Okay? So herb B1 is the receptor. It's a tyrosine kinase receptor. It works through K-RAS, again, very high yield to know that. It works through K-RAS as a second messenger system. So why is this important? The reason this is important is that you can block because I guess let me make things a little clear.

Her B1 acting through K-RAS promotes cell proliferation. And you know that this is something that cancer cells will want to take advantage of. So if a person has a cancer that overexpresses her B1, you can give a tyrosine kinase inhibitor to either block the receptor, right? And that's where her lotnip ERL-EL-L-O-T-I-N-I-B comes in. Or you can give a monoclonal antibody against that herb B1 receptor. In this case, it's a toxymab. So why do you think I went through the trouble of mentioning K-RAS as a second messenger in this system? Well, think about if you have a cancer that has a mutated K-RAS, then you will not respond to treatment with her lotnip or the toxymab. So why is this important for you exam? Well, this is important for your exam because guess what? Colon cancers, right? Many of them, at least a decent number of them, have those K-RAS mutations, right? So if you read first state, you probably remember something known as the adenoma to carcinoma sequence. The nomonic that people use to remember is like AK-53, right? So first you have an APC mutation and then after that you have a K-RAS mutation and then after that you have a P53 mutation. That's where AK-53 comes from. So if you have a K-RAS mutation, block the receptor, the upstream ERB1 receptor all you want, there's nothing's going to happen, right?

So they can give, I can envision this as a step one question where they talk about a person that has, is taking a lotnip, cytoxymab, they are not getting any tumor response, right? Think about a K-RAS mutation as the potential incitina event there. So, again, that's why colon cancers are not very responsive to these agents. Now the next drug I'll talk about is a T-RAS TUSYMAP, right? So T-RAS TUSYMAP, you've read about this before. It's a monoclonal antibody against the ERB2, okay? That's also called HER2 new. It's commonly expressed in many breast cancers. So T-RAS TUSYMAP blocks that receptor, right, so that you can basically decrease the growth of the breast cancer, although the thing is, yeah, it's good that, oh, I have a drug that can kill ERB2. The only problem is that having an ERB2 overexpression in breast cancer is actually a bad prognostic factor. That's actually a high-alt factoid to know for exams. So, one of the ways TUSYMAP works, right? So this is where they can bring in immunology on your exam. Is that it works through something called ADCC. ADCC stands for antibody-dependent cellular cytotoxicity, okay? Don't forget that IgG, and I believe IgE and C3 B also have the ability to do ADCC, okay? So, TUSYMAP, right, one of the ways it works is through ADCC, right? So let's let us talk about how TUSYMAP may use ADCC to kill a cancer cell. So the thing is, TUSYMAP, for example, could bind to the breast cancer cell, right?

And then, because TUSYMAP is an antibody, the constant region can be bound by receptors on the surfaces of certain cells, for example, like the natural killer cells, right? So if that constant region binds to a receptor on the surface of a natural killer cell, to be more specific, actually, the receptor binds to a CD16. Remember, CD16 and CD56 are the cell markers for NK cells. So you bind to the CD16 receptor on natural killer cells. When you bind to that receptor, you basically have the natural killer cell then beginning to release a lot of pfeffering. And that pfeffering can go and pfefferate the cancer cell. And then the grand sign goes into the cancer cell, activates caspiesis and causes apoptosis or cell death of those cancer cells, okay? And one key thing you want to remember with TUSYMAP is that it can cause dilated cardiomyopathy. In fact, the classic question is patient that is being treated with chemotherapy for breast cancer and then the ejection fraction goes down, right? Think about TUSYMAP. Also think about your antrocyclic because it so happens that antrocyclic is right, so like doxodonorobicin also used to treat breast cancer. Another way they can work this question is they can talk about a person that has breast cancer, her too new mutation and then they say in a prior to studying TUSYMAP, what is the next best step in management? This is probably more of a shelf exam or step two, CK or step three question.

But what they can do is they can say that like you I'll say for the most part, before these drugs are started on people, on college students to get echocardiograms on these people, right? To like estimate their EF, so that oh, if their EF is like 50% before they started the drug and then you now notice that oh crap, the EF is now 40% six months later, you should not that point that maybe I should probably stop this drug and maybe try some other agent for the scancer. So again, TUSYMAP causes dilated cardiomyopathy. The dilated cardiomyopathy associated with TUSYMAP though is reversible. When you stop the drug, the cardiac function comes back. Contrast this with your anthrocycling, right? So like donorobicin, doxoroobicin, these drugs cause dilated cardiomyopathy, but it is irreversible, right? So you basically have like permanent systolic dysfunction, although you could potentially have prevented this by giving a drug known as dexerzoxin. Dexerzoxin is an ion cheleter, so you're basically inhibiting that fentanyl reaction that is promoted by the anthrocyclin. Now the next cancer drug I'll talk about is retoximap, right? So retoximap is a monoclonal antibody against CD20, so basically, right? Because CD20 is found on essentially every B cell, it's very good at depleting a person's B cell population and it's very high to know that retoximap, one of the mechanisms it uses in its anti-cancer business is actually ADCC. That's why I described ADCC in the context of a trastuzumap.

Now on a, I guess on really fair note, EBV, right? Epitome bar virus, you'll remember it's one of the herpes viruses, it uses CD21, right? That's why it infects B cells for the most part, it uses CD21 to infect B cells and macrophages. Now the next cancer drugs I'll talk about are, you are aromatis inhibitors, right? So like drugs like anastrozole, letrozole, exemesting, right? So anastrozole, letrozole, exemesting. So the thing is, basically, if you want to convert androgens to estrogen, you use an enzyme known as aromatis, right? So if a person has an estrogen-responsive malignancy, like breast cancer, for example, if you give an aromatis inhibitor, you prevent the formation of estrogen and you basically make that cancer cell not get like growth signals, so you can treat the cancer that way, right? So again, aromatis helps you convert androgens to estrogen, right? So if, for example, you're going from angestine diet to estrogen or from testosterone to estradiol, aromatis makes that happen. Now what's the primary use of aromatis inhibitors on MBM Is? The thing is, you can use these drugs for like breast cancer, chemotherapy, in postmenoposal women. It's actually high you to know those points, not in premenoposal women, postmenoposal women. Why is that? The thing is, in premenoposal women, the primary source of estrogen is the ovary, right? Aromatis inhibitors are not going to do squat for you on that those circumstances.

But if your postmenoposal, the primary source of estrogen is guess what? You add depo sites, your fat cells, and fat cells express a crap ton of aromatis. So given an aromatis inhibitor, and other circumstances is a very good idea, okay? And the thing is, in general, you want to try avoiding aromatis inhibitors. Again, in premenoposal women, because it can cause very severe like hot flashes, right? So like these like menoposal symptoms. So again, premenoposal women, breast cancer chemo-prophylaxis, go with tamoxifen. Postmenoposal women, breast cancer chemo-prophylaxis go with an astrosol, your aromatis inhibitors. And the thing is, your aromatis inhibitors, because they actually decrease the formation of estrogen, they actually have like a lower thrombuane body risk and a lower endometrial cancer risk compared to a tamoxifen. But because they are depleting your pool of estrogen versus tamoxifen that has like some estrogen agonist activity in bone, your aromatis inhibitors actually have a pretty high risk of like joint pain and enthrownages, and also like osteoporosis, okay? That's actually a pretty high-yoda factor to know there. Now, next cancer drugs I'll talk about are the close cousins of the aromatis inhibitors. So these are drugs like tamoxifen and raloxifen, okay? So these drugs are serums, right? So they're like selective, what does this sermifondzane for? So selective estrogen receptor modulator.

So these drugs, they are used in again premenoposal women for breast cancer chemo-prophylaxis. And what are the key things you want to know about tamoxifen, right? So you want to know how it works by tissue type, right? So in the breast, tamoxifen is an estrogen receptor and tagonist. So it's great for breast cancer, right? But in the uterus, tamoxifen is an agonist, it's an activator of estrogen receptors, right? So you actually have, people have an increase in the metrocancer risk, it'd be take a tamoxifen although it's not a very significant risk, but it's significant for mbme exams, okay? So I would encourage you to know that. But in the bone, tamoxifen actually also activates estrogen receptors. So it actually decreases the ladies' risk of osteoporosis. In fact, this is one of the reasons why it's close causing a raloxifen is used for the treatment or the prevention of osteoporosis, but that's in like a very select population of individuals in general. A patient has osteoporosis, he probably want to put them on a biswasophane. Okay, now one other thing you want to know about tamoxifen is that it is actually more effective at preventing breast cancer if you compare with a raloxifen, okay? And again, because it has like estrogenic properties, you can have a thrombone-bolic disease, right? So like dvt, strokes, piz, if you're taking a tamoxifen. Now, let's compare contrast tamoxifen with raloxifen, right?

So the thing is raloxifen in the breast is an estrogen receptor and tagonist, but not as powerful as a tamoxifen at that business. So that's why raloxifen is not as effective in preventing breast cancer. But in the uterus and here's where things are different. Raloxifen is an estrogen receptor and tagonist. So it actually has no increased risk of endometrial cancer compared with tamoxifen that has an increased risk of endometrial cancer. And then in the bone, raloxifen is actually an estrogen receptor agonist, okay? So you can actually use it to prevent or treat osteoporosis. And then I guess the next drug I'll talk about is a drug known as full vestrant. Full vestrant, FUL, V-E-S-T-R-A-N-T. It's an estrogen receptor and tagonist. You can actually use it to treat like certain genecological malignancies. And then the next drugs I'll talk about are luperlyde and glycerylene. So luperlyde and glycerylene. Goccerylene is G-O-S-E-R-E-L-I-N. These are gene-rH analogs. Keithy owner, remember, if you give gene-rH analogs in a pulsatile fashion, that will operate the HPG axis. But if you give your gene-rH analogs in a continuous fashion, that will inhibit the HPG axis, right? So these drugs, if you give them continuously, that will inhibit the HPG axis and then cancers that are responsive to outgrowths of the HPG axis, will no longer grow, right? So like you can use them for prostate cancer, for certain gynecologic malignancies.

You can actually also use them to shrink fibroids, right? So like lyomyomas. So usually, before a person goes for lyomyomas surgery, right? You can actually give luperlyde for like six months to decrease the size of the fibroid by like 50%. Okay. And then the next drugs I'll talk about, like flutamide and bicarlutamide. So the all-ending amide. So flutamide, bicarlutamide. They are like hydrogen receptor antagonists. You can use them to treat like menastarica prostate cancer. And then the next drug I'll talk about is like finasteride, you testeride. Just think of them primarily as being used to treat BPH. But if sort of right, go with these drugs I've been talking about. So I'll just mention them here. So the thing is finasteride, you testeride, the inhibitors of an enzyme known as 5-alphoreoductase. So why do we care? The thing is 5-alphoreoductase helps us convert testosterone to a more like supercharge from testosterone known as DHT, dihydrotestosterone. It so happens that DHT is like the primary thing that promotes the growth of the prostate, right? Promotes the growth of the prostate. So if a person has BPH and they have insignificant symptoms, you can try to kill the growth of the prostate by effectively decreasing the amount of DHT in the body. And one very effective way of doing that is by inhibiting 5-alphoreoductase, which drugs like finasteride and dihydrotestosteride. You inhibite 5-alphoreoductase, you decrease the formation of DHT.

And in the long term, you can significantly shrink the prostate on that those circumstances. Now, one of the things I will say with that is, finasteride, you testeride, I use for the long term treatment of BPH. But if you want to like immediately help BPH symptoms, you want to give an alpha-1 blocker, right? So you want to give drugs like tam solucin, right? You can also give like a prazosin, doxazosin, the alpha-1 blockers, remember that prazosin, doxazosin, alpha-1 blockers both at the bladder neck, right? And at the blood vessel level, right? So they can cause like orthostatic hypotension. So if you want something that's a little more specific for the prostate, right? Like the bladder neck around the prostate, you want to give tam solucin, tam solucin works on alpha-1 AD receptors, which are only found around the bladder neck. And don't forget that tam solucin can also be used to treat nephrolithiasis, because again, by blocking those alpha-1 receptors, you'll put up the bladder neck. And people also say if you read the literature that it can dilate your eaters, so that can help you basically drain a kidney stone. And then the final, final drug I'm going to talk about is a clomifin. So clomifin, the big thing you want to know is that, I mean, think about it. Clomifin sounds really similar to moxifen or eloxifen, right? So clomifin is actually a serum, okay? The only thing is that it's more of a partial agonist that estrogen receptors, right? So think about it.

If you're a partial agonist, in the presence of full estrogen, you effectively actinazan antagonist, those estrogen receptors, right? So the thing is, clomifin is used to treat PCOS, because by basically being an antagonist in the brain, right? Like more upstream, right? So like in the hypothalamus, for example, you can basically remove that negative feedback of estrogen, so you have like more gene-arge postatility. And that can promote fertility in the setting of a PCOS, right? So basically, if a patient has PCOS, they're trying to get pregnant, just give them clomifin, and it helps in a great majority of cases, okay? So that's where I'm going to stop. And that's officially the end of on-pharmacology. I know today was kind of a lot. I probably talked about like 20, 30 different drugs today, but I promise you this is a very high yield, it's a very high yield podcast. In fact, I'll probably, when I'm putting this on my website, I'll probably call it like cell-ball, like a cell-ballgie podcast as well, because there's a lot of high yield cell-ballgie stuff that could be tested from this, and also from episode 70. And then before I sign off, just one again, throw this out there that I offered tutoring for step one, two CK, two CES, step three, medicine-entrining exams, and also the medicine-board exams. And I also prepare applications and help with interviews for like med school and for residency, so like ERAS and AMCAS.

So if you're not anyone that needs any of those things or friford, send them my way. I've done this for hundreds, probably like a couple thousand of people, so I'm pretty conversant with this. So just send them my way. The email is Divine Intervention Podcasts, so podcasts with an S at gmail.com, and I can sort of point them in the right direction. So have a wonderful day. I am super glad the Lakers are one yesterday. I am really hoping that we beat the team we're facing tomorrow. We beat the jazz, and then I keep climbing up that Western conference at table, and then win the MB finals and everything we owe to the world. So I'll see you guys in the next podcast. That'll be episode 72. Have a wonderful rest of your day and God bless. Thank you.

Intercalation physically stands between base pairs (e.g., ethidium bromide) to prevent bonding, while cross-linking chemically modifies DNA bases (e.g., alkylating agents) causing abnormal bonds (like G-T).

Acrolein. This metabolite is a vesicant and can be prevented by administering Mesna or vigorous diuresis/bladder irrigation.

Platinum analogues (cisplatin, carboplatin) and aminoglycosides (gentamicin). Vancomycin also shares this property.

Remember "V" for Vinca/Preventing Polymerization; then take the opposite for Taxanes.

Streptozosin (or other nitrosoureas like Lomustine).

The presence of an activating KRAS mutation, which bypasses upstream signaling blockade.

Alkylating agents (e.g., nitrosoureas).

It works through ADCC (Antibody-Dependent Cellular Cytotoxicity); it can cause dilated cardiomyopathy.

Fluoroquinolones.

Tamoxifen has an increased risk of endometrial cancer because it is an agonist in the uterus; Raloxifene does not increase this risk.

Finasteride or Dutasteride.

The MGMT gene must be mutated/silenced; otherwise, the drug's effects are undone by the functional MGMT enzyme.

All-trans retinoic acid (ATRA).

Alkylating agents (e.g., nitrosoureas).

It works through ADCC (Antibody-Dependent Cellular Cytotoxicity); it can cause dilated cardiomyopathy.

Fluoroquinolones.

Tamoxifen has an increased risk of endometrial cancer because it is an agonist in the uterus; Raloxifene does not increase this risk.

Finasteride or Dutasteride.

The MGMT gene must be mutated/silenced; otherwise, the drug's effects are undone by the functional MGMT enzyme.

All-trans retinoic acid (ATRA).