Transcript for:
Pharmacology I L2

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Knock on me. We won't have too many problems. Anyone confirm the sound's working? All right. If not, I'll just go with the assumption that it's working.

So looking here, Marissa says, good afternoon, would you mind going over dicloxacillin? It was indicated in a few derm conditions we learned in CMS. Yes, so dicloxacillin. if you recall, is one of those anti-staphylococcal penicillins. And so its role is fairly limited when it comes to how often you're going to use it, but it's very focused, meaning it's really used to treat MSSA, and that's kind of it.

So usually what happens is you'll have a condition where you're worried that maybe MRSA could be present. And so you'll start off with something like a vancomycin, for example, and then you'll see, okay, well, you know, a culture's come back and it says, oh, it's not MRSA, but it's MSSA. And so at that point, what you can do is discontinue the vancomycin, and then you could start on something like a dicloxacillin, oxacillin, nafcillin, any of those three would be reasonable.

The benefit of that is because Those anti-staphylococcus have such a narrow spectrum of activity. They're really geared towards MSSA specifically. You avoid putting selective pressure on a whole bunch of other bacteria, and you help to reduce resistance issues in the long term. So hopefully that answers your question. We'll cover some derm stuff here.

Let's talk about that. And if you have further questions about dicloxacillin, you can ask them there. I put up the...

Link for the chat, so if you want to click there, I'm happy. There's no drop frame so far, so I'm thinking whatever magic I did seems to be working so far. But let's get into it.

Let's talk about some derm meds. Here are my learning objectives for today, coming straight from your syllabus. And let's get into our introduction to dermatologic pharmacology. Now, I'm sure many of you, some of you, may want to go into derm.

Some people may cast dispersions on you saying, oh, you just want the sweet life. But my take is I say you get your you get your bliss. You chase that bliss down. I ain't gonna fall anyone for going to Durham. I teach for a living.

And any faculty members that give you any sort of any sort of shade or going to Durham should be like, dude, you teach like you got the sweetest job of all. Anyway, point being, though, is I've not done a lot of Durham in my particular line of work. It's not a particular passion I happen to have.

It is for my wife. I've tried to get her to give this lecture many times, but she refuses to do so. She has a public speaking phobia.

But I know enough about this stuff to at least be able to teach you effectively for our purposes here. The reason why I know that is because actually a couple of years ago, I had an actual dermatologist in one of my classes. And so he was from India, was coming over here to be able to practice.

And so he was going. to go to the PA route because that was the most kind of expeditious means of getting back into medicine but he was the expert he does he was a dermatologist so I say listen if I get anything wrong you tell me otherwise give me the thumbs up and at the end of it he gave me the thumbs up so those are my credentials I can at least say one dermatologist has approved this lecture but let's get into it so there are a lot of things to consider when applying medications to the skin um you can see some variability in response when we are applying topical medications here. So for example, you can see that drug penetration can be quite varied.

For example, places where the skin is thinner, you tend to see more permeability, meaning more drug can get through. And so when you think about medications applied to the skin, you think about them kind of just working at the skin level. But it's very possible for medications to permeate through the skin to get into the systemic circulation.

In some cases, that's what we're doing it for. So if we have like an estrogen patch, I don't want the estrogen working in the skin. I want it working systemically to treat someone's menopausal symptoms. Or if I'm using transdermal fentanyl, for example, I want that to get through the skin into the bloodstream to treat someone's pain, for example. And so which skin is going to be more permeable tends to be the thinner areas.

So for example, the scrotum, the face, the axilla, the scalp, thinner areas have more permeability. That will matter when we get into, for example, certain medications we don't necessarily want to get through the skin and into the systemic circulation. So this could also not only be a source for efficacy for the medications, but also possibly for toxicity side effects and things like that.

So the area where we apply it. is going to matter next up we're going to see that the concentration gradient will factor in here as well so how big of an initial concentration that we're giving will drive more drug across so one of the things you can see here is that someone was having difficulty with say steroid application or they were steroids not working as well because they're becoming resistant you can just give a bigger concentration and that will thereby force more drug across that's another way we could try to alter our topical formulation so you can see where we apply it matters how big of a dose we're going to give matters as well which seems intuitive dosing schedule you can find in some cases that the skin can kind of act as sort of a reservoir or a depot for the medications themselves and so as the drug starts to accumulate the medication over time it can sort of act like a storage spot where even if you don't apply it to the skin 24 7 Some of it can still kind of seep out from the skin reservoir into the bloodstream. And what that can mean is you can have maybe once daily dosing of medications that would otherwise seem to be fairly short acting. And then we have our vehicles and occlusion.

I say vehicles. I don't mean what you drove into campus today. What I'm talking about is what type of sort of what is the drug being placed into? Is it a cream, an ointment, a lotion? a gel, a foam, a tincture.

There's so many different vehicles that are out there. And these can also really dramatically alter the drug's permeability as well. They themselves may also be possibly therapeutic, where they can have moistening effects in some cases.

They may have drying effects. We'll go over the list of them here in just a second and try to compare and contrast those together. And as I said, the vehicle can be therapeutic.

The other thing to consider too is the occlusiveness. of the vehicle. When I say occlusion, it's when you apply it to the skin, how much of it's going to just sit there and just stay there. So if you were to compare, I'm sure most people have touched like Vaseline before or white petrolatum or petroleum jelly, whatever.

But it's a thick, fatty, oily kind of stuff. Substance. When you put it on the skin, it's not going anywhere. It's not going to evaporate. It just kind of sits there.

that is going to be much more occlusive than if you were to apply like an alcohol-based spray to the skin. That evaporates really quickly. It's kind of gone very quickly.

So the more occlusive something is, the more it's going to keep the drug there, the more it's going to cause that penetration to happen, which may increase the therapeutic effects of the drug, but can also in some cases lead to toxicity. Not only that, but also consider we can apply actual physical occlusion. So if I were to say apply medication to the skin and then apply, say, some kind of bandage or wrap around that, that thereby increases the occlusiveness as well.

I'll give you some examples of that here in just a bit. So we need to consider some things with the dermatologic vehicles here. So one, drug solubility in the vehicle. So if the drug's not soluble in the vehicle, it's not going to work. And some drugs may prefer more hydrophilic.

types of vehicles and some drugs may prefer more lipophilic but the vehicle needs to be able to solubilize the drug in order for it to even get to the skin to interact we'll also find that the ability for that vehicle to hydrate the stratum corneum can also enhance penetration so if you have some areas of skin that are very dry and hard that's difficult for things to penetrate through but if i apply something that's going to hydrate it that helps enhance penetration and then we need to consider the stability of the drug in the vehicle so anytime we introduce things like water into a formulation, that is going to be an area where things like bacteria can start to grow. You can start to see drug degradation in some cases. And so this is where we oftentimes need to include things like stabilizers or preservatives.

in order to keep the drug sterile and stable. So that way it's effective and doesn't cause like an infection for the patient there. So going from kind of our most drying to the least drying vehicles here, you can kind of see the spectrum.

So you want to have a general sense for these. So if I said, oh, the patient has, you know, a lesion that's oozing, has been vesiculation, crusting. which of these might you want to use versus if I said, oh, it's very dry, scaly, which of these might you want to use?

So things that are going to be more drying tend to be, one, tinctures, absolutely there because they tend to include alcohol. Things like lotions, gels are going to be the more drying side. Going on down the list here, we're going to see things like creams, paste, ointments tend to be least drying, ointments being on the far end there.

And so there's kind of an old adage, and I think dermatology people probably don't like it because it's kind of painting with too broad of a brush. But we're going general here today. And so they say, you know, if it's dry, you want to wet it.

And if it's wet, you want to dry it. Meaning that if you're having very dry, scaly looking skin, apply something that's going to be a more moisturizer. And if it's having a lot of fluid, ooze and things like that, try to dry it out.

And so what you can do, one of the decisions you're going to have to make is, okay, what type of vehicle am I going to go for? Is a cream more appropriate than a tincture versus an ointment versus a gel? So how do we make that decision other than just if it's dry, wet it, and if it's wet, dry it, right? Here are a couple of comparisons.

If you notice here, we have four columns. We have the creams, ointments, gels, slash foams, and then you get into like your lotions, solutions type of products here. And let's look at the physical basis. For a cream.

This is going to be more so an oil and water emulsion. And because it's oil and water, that will clue you into the fact that it's more water-based. There's some oil in there.

It's an emulsion, but it's mostly water-based. And you can see in the solubilized medium here, it's greater than 31% water. So let's look at some things here. The pharmacologic advantages here, it can leave some amount of drug on the skin. So as the cream base starts to evaporate, some drug is left over on the skin.

So that can help extend. duration of action right other benefits here spreads and removes easily no greasy feel that can be another consideration for your patient is okay well do they like the feel of it because i don't know i don't like oily greasy feeling stuff sticks on your hands you gotta go use soap and water get it off like it doesn't feel great but a cream or something could be much more preferable to patients in some cases location the body can use in most places it does need preservatives And so because of that high water content, you need the preservatives to keep it sterile and stable. And so this could lead to potentially maybe a side effect due to an inactive ingredient, for example.

Right. So you need to consider that occlusion levels fairly low because there's not that high oil content. It's just that oil and water because the water evaporates.

Occlusion is not great. We're not going to worry so much about the humectants portion here. It's kind of a... very esoteric term we don't need to worry about so compare the cream to the ointment those are kind of the two two big kind of um main vehicles you're going to run into you'll see creams you'll see ointments um ointments tend to be a water in oil emulsion so now because of that the water content is much reduced but the oil content is much higher and so here you can see some advantages that it has a protective oil film on the skin it does not evaporate easily And so because of that, it has a nice, just thick layer that's just going to sit there.

Spreads pretty easily. However, it's going to have that greasy feel. You can even see cases where it stains the clothes, which may not be great for the patient there. Notice from locations you want to avoid intertriginous areas of the body. Where do I mean by that?

I mean the groin, the axilla, anywhere where it's skin-on-skin kind of contact. Because that increases the occlusiveness and that can increase drug penetration, which in some situations... may not be desired okay um occlusion here much more moderate to high versus low for the creams and so those are kind of the big differences there so if the patient doesn't really like that greasy oily feel then maybe a cream is more appropriate for them or if they need that occlusion maybe an ointment's more preferable right anyway so then let's compare that to some gels and foams here you can see a water soluble emulsion here these are non-staining they're greaseless Um, think about the areas where applying the drug as well. So for example, a foam may be preferable to the scalp, or if you have areas where there's a lot of hair, because it's easier to work through there than if you were to apply, you know, if you took like an ointment. to the hair i mean i guess if you want to like give the patient a mohawk or something that would work pretty well but if you're trying to get the drug to the skin the scalp underneath this is going to be pretty difficult so phones could be pretty useful for that note here as well again needs preservatives because the water component there if there's an alcohol base those tend to be drying because it evaporates so quickly it'll take some water with it and so anytime you have alcohol involved it is pretty drying for the most part here and then if we're looking at things like lotions or whatnot these are typically going to have Um, very little in terms of occlusion, it will evaporate away here, but again, could be useful for things like the scalp, for example, here, it'll just depends on the situation.

So these are kind of the big kind of comparison points between your creams, ointments and gels, foams, types of products there, um, to have a general sense for what are the key differences here between the two? When might you want to use one versus the other? If it's a particularly dry type of skin, you're applying the drug to go with something that's going to be more hydrating.

If it's something that's going to be very wet. and then try to use something more dry, like maybe an ointment or maybe a, you know, alcoholic-based tincture or a foam or something like that. Anyway, so let's get into some more specifics here. Let's talk about acne in particular. So this is a multifactorial disease here, meaning there's a lot of components to it.

There could be environmental factors, genetic factors, your race, hormones, diet can all play a role here. But... There's four main sort of pathophysiologic steps here.

So one of which is going to be this increased sebum production. I mean, the oils are going to be produced within the skin. You'll then see also this alteration and the keratinization process.

Basically, you're going to have this hyperproliferation. They're going to basically cause a closure of the pore. By doing this, having a sebum-filled kind of occluded pore, you're going to see that anaerobic bacteria like... like propionibacterium actes here, are able to then start to grow and replicate.

And then from there, your skin wants to, your body wants to fight that infection. And so you're going to start to produce a bunch of inflammatory mediators. And then you get the inflammation component there.

And so you're going to find that all of these different steps here tend to perpetuate one another, leading to worse and worse in acne, which is not great. Again, there's other contributory factors as well. So, for example, areas where there's like a lot of pressure or friction.

So, for example. you know we think about acne usually like in your adolescent young adult types of populations um where the hormones are going to be raging um maybe they're participating in sports where they don't have shoulder pads on anyway see kind of like regional acne in those types of areas there um the season could matter so for example tends to get a little bit worse in the winter time versus improvement in the summer kind of just depend and what's also interesting i find is that you know people worry about having breakouts when they're really stressed out And you think, okay, well, why would that be? Why would you have more acne due to stress?

Well, when you get stressed, you produce much more cortisol. And cortisol is a type of glucocorticoid, which is going to be able to suppress your immune system. So now that bacteria, which may have been fought off before, now can proliferate and now cause these outbreaks of acne.

So stress can matter as well. You guys don't know anything about stress. You're just in PA school. It's probably one of the least stressful things. you could possibly do with your life, right?

That's what I've heard. Not really. So anyway, like I mentioned, with the pathogenesis here, we're going to see this pooling of sebum makes this anaerobic environment.

So you're going to get this proliferation of the bacteria, produces acne here. The body fights that, so it's going to make a lot of inflammation, right? Part of that, when you have these neutrophils invading, T-cells and whatnot, you're going to see this lipase from the bacteria start to hydrolyze triglycerides and free fatty acids.

And so this ends up leading that... keratinization process we talked about so you get that kind of micro comedone formation that happens there where again you're blocking off the pore everything's nice and anaerobic and the bacteria love to grow there and through the action of the immune system you start to generate pus and whatnot as a result of that and in cases you may find some of it being more versus less inflammatory so for example non-inflammatory types of acne may have a kind of these like open or maybe closed comedones versus inflammatory you get much more of these like big papular pustular you these nodular lesions that can form tend to be more severe. And so in those situations, we may need to kind of guide our therapy to try to deal with that inflammation a bit more versus maybe using less severe sort of options.

We'll kind of go through our different options available to us here in just a second. So anyway, looking at this, you get the abnormal keratinization from the microcomodone, the increased sebum production here, and then eventually get into things like papules and pustules. And...

nodules and cysts oh my all this can be forming from these different steps here along the pathway and just pictorially what this looks like again you can see the sebaceous gland here producing the sebum things are going to get to start closed over here you're going to see the bacteria growing And eventually the immune system just comes in and just cause a big inflammatory kind of response there. Not great. And of course, you know, our natural inclination when we see a zit is we want to pop it.

And that tends to make things worse. And it just gets worse and worse there. So we want to try to interrupt this as best we can.

It's also important to consider when we get into talking about different disease states. I want to always implore you to look into. are there drug-related reasons for this thing to pop up? Because what I don't like to see is a patient has a drug-related problem that no one's really recognized yet. So then you decide to treat the side effect of one drug with another drug, and that then causes other side effects, which you then treat with another drug, and it can perpetuate itself, which is not great.

We want to try to disrupt this as best we can. And so the medication list is very often... disregarded when trying to come up with a diagnosis for your patient but check out the med list see if there's anything on there that could potentially be playing a role for your particular patient whether it's a derm thing cardio thing whatever the case may be so in the case of drugs that can induce acne we have several that are available to us so one for example here are systemic corticosteroids so we see this for patients who are taking you know kind of chronic steroids which are suppressing the immune system that then leads to formation of this acne again which is a common side effect we know about. And notice here about two to six weeks after initiation of therapy.

So these are patients taking much more chronically. And maybe you're thinking about patients like autoimmune conditions, like say rheumatoid arthritis, for example. They may be more prone to this.

Or if you're like juvenile rheumatoid arthritis, which you may have as a young adolescent, for example, during puberty, that could be a double kind of whammy there. Hydrocortisone is not going to be really likely to cause this. We'll talk about steroids later.

So hydrocortisone is kind of the wimpiest out of the bunch here. So it's not usually going to be too big of an issue there. And then if you were to say, okay, well, the steroids causing the acne here, one you need to consider, well, do we really need the corticosteroid? In many cases, the answer may be yes, but could we reduce the dose or whatever the case may be.

But if you remove it, what's actually interesting here is it actually causes the acne to get worsened initially. And you're like, okay, well, why is that happening? And that's because as you... start to remove the corticosteroid, the patient's immune system kind of starts to come back to life to a degree and gets more active and is going to cause an increase in the amount of inflammation that you see there.

So it'll initially cause the acne to get worse and before it gets better, which is counterintuitive. Other agents which have been known to cause acne can include antiepileptics, which we use to treat seizures, drugs used to treat tuberculosis, lithium for bipolar disorder. So anytime you were considering drug induced acne, look for some of these agents here. And again, if someone has a seizure disorder, I don't necessarily want them to stop taking their seizure med because they have acne. Again, you're weighing the risk versus the benefits.

I'd much rather the patient have acne than have a seizure, right? But if we could consider switching to a different agent, which is maybe less likely to cause it, that could be a preferred option for you, right? When it comes to tuberculosis, you kind of don't have a lot of options there.

So again, you may just be having... something you have to just kind of treat through until the patients are off their tuberculosis medication, right? So again, your miles may vary for some of these.

So treatment here, acne tends to be more of a chronic kind of condition. We'll see that our initial therapy is going to be early and aggressive to try to get things under control. And then we can try to scale back towards maintenance therapy.

And so for a lot of these chronic conditions we'll look at throughout our year together or so is that they go through. ebbs and wanes or waxing wanes i should say where as the disease state gets more intense you scale up your therapy or if you have like a flare up you're going to scale up your therapy and as things start to die back down then you pull the therapy back and so you have this kind of ebb and flow that happens here um to where you want to get on as small of a medication as possible as meaning as low of a dose as few meds as possible But as those flare-ups happen, then you have to scale up therapy to meet that, but then you want to kind of calm back down. And so patients may go through this kind of process here where if they're having a flare-up, they'll say, okay, well, I need to go back on this.

And then as things start to die down, they can then scale it back. So you'll see that kind of theme as we go through a lot of these different chronic conditions here, going from more aggressive treatment to maintenance therapy and back and forth. So our goals here, we'd reduce number and severity of lesions, hopefully slow down progression signs and symptoms. I'd like to... limit recurrence.

We want to prevent long-term scarring that can happen here, disfigurement, and avoiding psychological suffering. I don't know about any of you, but having acne as a teenager kind of sucks. You're worried about what people think about you, even though they're probably not thinking about you.

Again, it can cause a lot of psychological suffering there. We'd like to avoid that if we can. Our treatment here is going to be focusing on the microchromodone. So if we can eliminate that follicular occlusion, which sounds like a cool jam band name or something, we can arrest the whole cascade.

Basically, by opening up the comedone, having this occlusion reduced, opening that thing up to air is going to help stop the rest of the cascade here. We'll look at our both pharmacologic and non-pharmacologic options we have to us. And in some cases, we may need to use multiple mechanisms of action because using different drugs with different mechanisms tend to synergize pretty well. And we'll find that by targeting different pathologic steps or pathogenic steps, we can be able to do that synergy quite nicely. Mild to moderate cases here, topical therapy usually works for most individuals.

For more moderate to severe cases, systemic therapy is going to be necessary. Usually going to be oral medications patients will be taking here. Now, you also want to consider the extent of the disease, meaning like how much of the body is it actually covering? So for example, if it's just like to the face, that's a relatively small area versus if it's like the face, the neck, the shoulders, the chest, the back, that's going to require much, much more drug to be applied there. At a certain point, it gets so extensive that logistically it's very difficult to keep up with using topical therapy.

That could also be another reason why we may switch gears and utilize our systemic therapy. The downside though, is that systemic therapy. is inherently more likely to cause side effects because you're applying the drug to the entire body, not just to the skin.

And so that's always going to be the trade-off we have here between the convenience of using an oral product, because I can just take a pill, it's easy to do, versus applying a cream to the face, applying cream to the chest, the shoulder, whatever the case may be. So logistically, there's some consideration there as well that we'll get into. So for non-pharmacologic therapy here, we're going to see that... Cleanliness is next to godliness, as they say here.

And so by utilizing our cleansing type of products here, usually soap-based products are going to be the surfactant system. What they're going to do is basically disperse and remove fats and oils from the skin surface itself. The downside you're going to find, though, is that a lot of these products tend to be pretty drying or irritating, which itself could also exacerbate the acne. So we need to balance that. desire for cleanliness, and also the drying and irritating factors of the products themselves, the cleansing products.

Soaps by themselves, while possibly effective, typically are not the best products we're going to use here because one, once they're rinsed off, there's not any active product around. So that oil production can start to kick back up again. And we can find that high pH, which a lot of soaps by their nature will have higher pHs, tend to be more alkaline.

They can actually degrade the activity of some of the other products we're going to use here. They also tend to be a little bit less tolerable than skin as well. So generally, the needle to thread there is we don't want to wash too frequently. You want to do it, but you don't want to do it too much.

Usually, twice a day is sufficient. Once in the morning, once at night, and you're good to go there. Let's get into the topical therapy now.

So as I mentioned, this only works where it's applied. So it requires application to the full surface area. That kind of makes good sense.

Most of these though will cause skin irritation. Just by their nature, they cause skin irritation. And that may be a reason why patients want to discontinue therapy early.

We can, in some cases, try to mitigate this by starting with lower strength products and then gradually increase. So one caveat or one kind of mantra that I'll use a lot throughout the class is start low and go slow. For these chronic conditions, it's more of a marathon and not a race. So there's no need to go, you know, super, super aggressive to cause a bunch of side effects. Yeah, it's effective.

But, you know, if it's so intolerable to the patient, they feel miserable. They may not want to stick with it. And, of course, compliance is always going to be the name of the game here. If they don't stick with the medication regimen, it doesn't matter how great it is, if they can't stick with it, it's not going to work for them, right? So starting low and going slow and gradually increasing to see what the patient can tolerate may be necessary here.

And if we can avoid using alcoholic-based solutions, that can also be useful because, again, alcohols tend to evaporate very quickly. They draw water with them, and so those tend to be more drying. So we'd like to avoid those the best we can. So as you can see here, there are multiple different medications we're going to have available to us. that we can use to treat acne, we're going to see that they will target specific steps along the process here, as we'll see.

So for example, something like benzoyl peroxide, topical antibiotics, they treat the actual bacteria themselves. That's great. Some of these will actually be able to cover multiple steps though.

So for example, benzoyl peroxide can also affect the keratinization of the follicle to prevent that to kind of open things up. So you may have multiple medications or one medication that can treat multiple steps of the process. And that tends to be pretty useful just from a utility sort of standpoint there.

All right, so let's start with benzoyl peroxide. This is kind of like the first line. And another thing to always consider too, when patients come to you for a condition is you want to consider, Hey, this is probably not like the first time the patient's dealing with it. They've probably been dealing with this for a bit of period of time here.

What have they already tried? Because so many different products are available for acne in particular over the counter. They've probably tried some stuff before. And so you want to figure out what worked well for them, what didn't, what made things better, what made things worse. And because if you try to start the same thing they've already tried and it didn't work for them, then they may think that you weren't listening to them or that you don't know what you're talking about or who knows what.

So figure out what they tried before and again, go from there. So first off, we're going to start with benzoyl peroxide here, which again, most patients have probably tried at some point, but can serve as sort of like a backbone to eventually add other things onto potentially. And so what this is going to do is get through the stratum corneum.

And then it gets converted into benzoic acid. And so that's kind of the active form of the drug here, where it will actually have antibacterial activity against the P. acnes. And it also causes kind of a peeling and comedolytic effect, meaning it deals with that, kind of breaks down that abnormal keratinization covering up the pore.

It will open things up, so that way some air can get in there. It will help to prevent the bacteria from growing so much. We'll start with low concentrations initially, like a 2.5% or so.

And then as we see how they tolerate it, we can increase the strength and the frequency. And these are available over-the-counter, so patients probably try this at some point. And then in some cases, we may actually be able to get away with combination therapy. So you may see combinations with certain antibiotics.

These are going to be prescription only, but you could have like benzoyl peroxide plus erythromycin, for example, or clindamycin plus benzoyl peroxide. And that just helps to simplify the regimen to a degree. But we'll talk more specifically about antibiotics here in just a minute.

Adverse reactions here you can run into can... Bleached hair can bleach the clothes. And depending on where it's being applied to, if it gets close enough to mucus membranes, it can cause some irritation there.

So, for example, if they're applying it like underneath the end of the nose and actually get a little bit in there to mucus membranes, that can be irritating for sure. So when applying this is maybe something where I say, OK, well, you know, watch out for the hairline. You know, if you're going to be going to bed before putting this on, make sure to use kind of a ratty T-shirt.

Don't wear like a nice. nice clothes because it can cause that bleaching effect there as well somewhat similar to benzoyl peroxide is a product called azelaic acid while not fully understood we think that it probably has some antimicrobial activity and interestingly too this is thought to also inhibit the conversion of testosterone to dihydrotestosterone so how does that factor in well if you recall we mentioned you know this is a condition that you know you think a lot about and adolescents and young adults and what's going on around that time well puberty is happening around that time and so this new production of testosterone can sometimes exacerbate acne well why is that well it's not the testosterone necessarily but it's the conversion of testosterone into a product called dht or dihydrotestosterone and in fact this is the more potent kind of androgen androgen is the term we use to refer to like these masculinizing types of hormones like testosterone and dht you And so DHT has a number of different effects here. In particular, it causes growth of the prostate, for example, causing things like benign prostatic hyperplasia.

But it also is responsible for causing acne or at least contributing to acne. And so, for example, if you ever see bodybuilders who are utilizing performance-enhancing drugs, they oftentimes will complain about acne because they have this higher production of these androgens, which then further worsen their acne. So by using azelaic acid, if it can help to prevent that conversion of testosterone and DHT, it's thought to help reduce kind of the hormonal component of acne to a degree, which may contribute to its efficacy there. Okay.

So again, start once daily and then see how they respond to it. It may increase up to twice daily. Skin irritation still is going to be the most common side effect you're going to run into.

Generally, this helps as time goes on, it does improve. You know, you could also utilize, you know, things like emollients as well. So if you have like an aquaphor or, you know, some sort of cream you can apply as well afterwards, that can also help out with the dryness and the irritation. And then also this can cause some hypopigmentation, which may be actually being used for that specific purpose there. So this could be a side effect that also may be a beneficial effect for some individuals depending on their situation.

Okay, so somebody had a question here that said, for benzoyl peroxide's OTC strength less, could the higher concentration be more beneficial than what patients may have tried at home? Absolutely. So when you're looking at OTC versus prescription-based products, you tend to find that the prescription-based ones will have higher concentrations in a lot of cases.

I'm actually going to try to pull up the monograph for... benzoyl peroxide just kind of give you an example and and so you're absolutely correct that having those higher concentrations may be useful in those cases where the otc stuff didn't really work so in that case you may have a patient where you're like okay we're going to try benzoyl peroxide and they're just like well my guy already tried that out why why would we use this again and so let me give you a example here um so if you notice here are the different doses forms you in the U.S. here. So you can see there's variable concentration.

So you can go from like, say, a 5.2 concentration as a foam or a cream here, get the 10%. So it's double the strength there. You could see, you know, 2.5%, 5%. So some of these are going to be less concentrated, and especially for those ones that are going to be available OTC. But some prescription-grade ones will have a higher concentration.

And so that could be something you consider utilizing those patients there. So like I mentioned, if they're kind of like, well, Why am I going to use that when it didn't work previously? And you say, well, actually, we're doing a totally different dose.

We're actually going up on the dose here, and this may be more effective for you, right? It's not like there's anything special about the prescription stuff. It could just be that, yeah, we just have a higher concentration in general, right? Does benzoyl peroxide come in an aqueous base only? So I wish, pull that right back up here.

So not necessarily. So if you can see here, if we're looking at the different dosage forms, here's one that's going to be gel-based. So it may be more aqueous in nature. Here's a foam.

Here's a cream. I don't see any necessarily more oil-based ones just looking at this. I don't notice there's a lotion.

So generally, it's going to be more water-based. That's probably good because you don't necessarily want this stuff just kind of sitting on the skin for long periods of time just because of the irritation it could cause. So from that standpoint, they tend to be more aqueous in nature, I would say, for those bases.

Maybe there's like a custom compounded version somewhere who could, who could say, right. All right. So talked about as like acid. Now we get into the retinoids. Now we're kind of stepping up our game a little bit from your baseline, kind of like benzoyl peroxide that most people have probably chosen.

Now we get into the retinoids, which for a while, things I tried to know and actually were not available over the counter. I remember when I went on a cruise with my wife very early on in our. marriage we've actually our wedding anniversary is coming up this weekend we'll be married 11 years on the 31st if you can believe that um and so we went on a cruise very early on we were in somewhere in the bahamas and went to one of the pharmacies there and it was wild because there's a lot of stuff that was over the counter there that was not so in the u.s so for example voltaren gel we were able to get without a prescription um like you could get like uh tyrol number three which has a codeine in over the counter and you could also get retin-a you which is another name for retinoic acid. And so that has changed as time has gone on, showing our age, unfortunately, but things change, right?

And so now you can get some forms of these topical retinoids available over the counter, but again, stronger versions are going to be more likely to be in the prescription-only kind of realm, okay? So anyway, so topical retinoids, these are basically going to be sort of this acid form of vitamin A. We don't know really why, but... We do see that by applying these, we get this correction of the abnormal follicular keratinization.

So you start to have that kind of comedolytic effect to some degree. You start to see reduced P. acnes count. So it has some antimicrobial activity and it overall can reduce inflammation. So if we're having patients with non-inflammatory, this comedonal acne, this tends to be first line.

And so you can see this being used maybe in lieu of something like benzoyl peroxide. maybe some cases in concert with, but there's some caveats we're going to look at here in just a second. Other things you may see this used for can include things like wrinkles, dispigmentation.

So, so from other, you know, aesthetic purposes, some people might be using these products here just to help reduce like, you know, signs of aging and things like that. So looking at topical retinoids here, we're going to see pretty significant adverse effects as compared to your more kind of minimal kind of like benzoyl peroxide type side effects so you're going to see more erythema you can see desquamation burning stinging so this does reduce with time as patients are applying this consistently but also using hydrating emollients things like an aquaphor can be useful here to help reduce some of that side effect you can also see photosensitivity So in the areas where this is applied to, you'd want patients to either use sunscreens or to cover up if they're going to be outside, because otherwise it can be more prone to sunburns there. And we want to avoid this during pregnancy.

So as you see here, we can see this is an acid form of vitamin A. And basically, any time you are dealing with a fat-soluble vitamin, you want to stay away from pregnant patients. So for example, you don't want to mess with vitamin K. You don't want to mess with vitamin A or the other ones. So it's ED.

So A, D, E, and K are your fat-soluble vitamins. You don't want to mess with those in pregnant patients because the fetus needs those vitamins in order for normal function. So while the pregnancy risk is going to be fairly minimal with topical application here, tritogenicity or causing harm to a fetus is one of those things where I'd rather be safe than sorry. So it's one of those things where...

So patients, especially like, you know, pregnant moms, there's a lot of mommy guilt that goes into pregnancy where you worry every little thing possibly can have a negative effect. And so you're like, you know, you're very risk averse when it comes to pregnancy in a lot of cases. And so you worry about, well, what if this could cause harm?

Even if it's a very remote risk, you'd rather be safe than sorry in certain situations. Now, if it's like a life or death situation for the mom, well, then we may need to take that risk. But for acne.

Probably not going to be a life ending sort of condition. So in those situations there, I'd probably err on the side of avoiding these products here just due to the remote risk of harm to the fetus there. Because I'll tell you what, you know, when it comes to things like statistics, you could say, hey, this is a one in a billion chances things are going to happen to you. But if it happens to you, it's no longer one in a billion. It's one in one.

It happened to you. And so you don't want to be in that situation where you're like, well, if only I had avoided that. topical retinoid why was i so vain why did i worry about my skin being clear and free of acne that can be a big consideration right that guilt could be something people may want to avoid for sure and avoid potential harm to a fetus so anyway something to consider there's even more tritigin stuff we're going to see in just a second um we get to some of our top our systemic therapies so tritinoin itself is photolabile meaning you You don't want to put it on during the daytime. We could be exposed to a lot of sunlight.

So you do want to apply this nightly. And we can find that if you apply benzoyl peroxide at the same time as a tretinoin, this does inactivate it. So this could be a situation where you may prefer using benzoyl peroxide like in the morning and then like tretinoin at nighttime, for example. So separating those out could be important there.

Then to get into some other topical retinoids, you have things like adapalene or differin. This is another fairly common one we see being used for acne. It tends to be less irritating than something like just a straight tretinoin, so this could be preferred there.

And then we get into some other agents, things like tazeratine, allitretinoin, and bexarotene. Some of these are going to be more special to use cases. So, for example, certain types of cancer, these could be used to treat, or things like psoriasis, for example. So these are going to be less commonly used for your run-of-the-mill acne cases here.

But certainly tretinoin and adapalene, you're going to see kind of like your... Typically, your stable type of medication you're going to be using there. We also then have some topical antibiotics here. So, for example, plenomycin and erythromycin tend to be fairly effective here.

One thing you're going to notice is that the benefit of topical antibiotics is they don't cause a lot of systemic side effects. They tend not to be able to penetrate the skin all that well, leading to better safety profiles. So, for example, someone taking topical plenomycin, I'm not really worried about them getting C. diff.

because it's not getting absorbed. It's not affecting the GI tract bugs, right? The normal flora of the GI tract, I should say.

And because we're applying something to the skin, the concentrations you're getting are way higher than you would expect to see by taking a tablet of clindamycin, for example, or capsule clindamycin. So the concentrations locally are much higher, leading to increased activity. This can be overcome by resistance, and it's something we're seeing over time. is that efficacy has been getting worse just due to resistance to the bacteria.

So again, your myelos may vary in terms of how well this is going to be working for your patient. And again, acne is not something you're really going to culture and determine resistance rates. You're just going to try it out, see if it works for your patient.

If not, then move on from there. So then what do we do when topical treatment is not enough? This is where we start to switch over and consider some more systemic types of therapies here.

So first one here we're going to look at is isotretinoin or Accutane. This is kind of like the nuclear option. This is like kind of the strongest thing that we have to treat acne and really should be reserved for more of those severe cases where topical therapy, things like systemic antibiotics really aren't going to be sufficient.

And so the reason why that is, is because of the side effects that it has. and just the logistical sort of challenges with even getting access to the drug in the first place. Okay, so this is the first drug we're looking at that has what we call a REMS program, R-E-M-S. And what that stands for is Risk Evaluation and Mitigation Strategies. So what that means is that the FDA has noticed that there is a potential side effect here that is so severe they need to put a certain program in place to make sure the patients are going to be At little risk as possible for the severe outcome.

And it's different for different drugs. Some drugs have a REMS program because they cause agranulocytosis. This one in particular is because isotretinoin causes severe tritogenicity leading up to death of the fetus. Very, very severe negative effects on the fetus. So we want to make sure we never give this to a pregnant patient.

And so you can see the iPledge system is what we use for isotretinoin. They're committed to pregnancy prevention, which is also the motto I have for my two young daughters. Not before they're 30. No pregnancy whatsoever. I'm just kidding.

The point being is that because we know that this has the tendency to cause really negative effects on the fetus, and because think about the patient population we're using this in, young adolescents, young adults, hormonal individuals. I don't know if you've ever met an adolescent before, but they oftentimes have more time than sense and may make rash decisions about things like sexual activity, for example. So pregnancy could be a potential risk here.

And so what we do is we have this iPledge program where the provider has to be signed up with the program, the patient signed up, and the pharmacies will be signed up to this as well. And basically, you have to go through certain educations. You have to have routine pregnancy testing done, assuming the patient's capable of becoming pregnant. And if you don't follow these rules, you will then go to the pharmacy to pick up your prescription. Pharmacy says, I can't give this to you.

The system won't let me because you have not fulfilled the requirements here. And so you say, well, that's preposterous. I need my medication. And again, it's not, you don't need that bad.

So you got to go through the process here. This is like a legal kind of thing we have to do. It's even possible for men to be able to transmit some of the drug. and things like seminal fluid as well, we need to be considerate.

So they also need education as well. Make sure you're using different forms of contraception, making sure you're educated about actually using that contraception and all that. So otherwise, this is absolutely contraindicated in pregnant or breastfeeding patients here, okay?

I had a train of thought, and it just like derailed completely. I don't know where I was gonna go with that. So in that case there, we can see isotretinoin usually effective within about one to three months or so. Other adverse effects. This is really, really rough on the skin.

Very effective, but very rough on the skin here. We get this retinoid dermatitis. See a lot of erythema, pruritus, scalene can happen here. You get photophobia because it affects vitamin A in the eyes too.

If you go back to your ocular physiology, we know vitamin A is necessary for things like rhodopsin production and whatnot. So you can actually see photophobia as a result of this. You get sore joints, headaches. Even like your nails and your hair can be affected by this.

You can see changes in your serum lipids. And we also worry about signs and symptoms of depression. So this can actually affect mood, can cause worse depression for patients, or may kind of uncover depression in patients who may not have had a diagnosis beforehand. So there could be risk if patients have like a history of like suicidal ideation or self-harm or things like that.

Isotretinoin is probably not a thing I want to use for them, right? So a lot of considerations. Like I said, this is the nuclear option.

This is like the strongest thing you can get basically. And so you want to make sure patients are well prepared for here's all the side effects. Here's potential dangerous things. Let the parents know if there's, or, you know, caregivers, whoever say, Hey, look for signs of depression, things like that, which I think most teenagers probably have some, but if it's getting worse, you should look into that.

If you haven't seen inside out to yet, I should probably check that out. I think it's a pretty good representation of being adolescent and getting ready for puberty to start and all this kind of good stuff. But regardless, you know, a very factored drug, just a lot of caveats to it.

We also have systemic antibiotics that we can use. This is good for, again, more extensive disease, more difficult to treat disease cases here where maybe topical therapies just aren't going to be enough. This is probably to be used before you get to isotretinoin just as a trial to see how it's going to work.

We do like our tetracyclines the most common for this just because they're very safe, they're very effective for the most part, and they're cheap. They're pretty old drugs. You get these relatively cheap at the pharmacy. Couple caveats with using tetracyclines. One, make sure that they're not going to be taking this with like calcium or iron-based products.

Because again, they will chelate in the GI tract and not get absorbed. And again, we'd want this to be avoided. For long-term use, kids less than eight who have not had their adult teeth come in, and then pregnant women as well.

Some alternatives we've used in the past have included things like Bactrim, Azithro, Ciprofloxacin. But for simplicity's sake, I say stick with the tetracyclines first, unless you have some contraindication or some reason you could not use that. Other therapies that have been used as well can include things like salicylic acid. So this has been used for many, many years, although not necessarily with the greatest evidence to support it. We do know it has keratinolytic effects.

So for example, you could apply salicylic acid to like a wart, for example, to start to break down that tissue, which could have similar effects on the comedone. Some antimicrobials, some anti-inflammatory activities that could be useful there. We also then have antiandrogens like our drug spironolactone.

Now, we'll cover this more when we get into discussing some of our cardiology medications. But spironolactone, when used topically, is interesting because it works basically as a partial. androgen receptor agonist.

What I mean by that is it works kind of like sort of a weaker version of something like testosterone or dihydrotestosterone. So why that could be beneficial is if you have someone who is producing a ton of testosterone, more so than say their peers, for example, that may be contributing to their acne. So by using something that's a partial agonist, which can displace the testosterone, you overall draw down the overall testosterone activity in the skin. So you go from, say, like, you know, 100% down to, like, say, 50%. By reducing the overall testosterone activity, you actually end up getting less of that androgen effect, and that can help to improve the acne as well.

We'll look at spironolactone when taken systemically and some of the different side effects, because it gets a little more complicated there. But generally, that's why we're using an anti-androgen. as topical therapy because they help reduce overall testosterone activity there. And then we get into oral contraceptives. And so these are typically based off of an estrogen and then a progestin component.

So for example, ethanol estradiol is the main synthetic estrogen that we use in oral contraceptives. And then norethendrone is just an example progestin that we use there. And so by utilizing this, this can help to kind of regulate hormone levels because instead of relying on the normal menstrual cycle to produce things like luteinizing and follicle stimulating hormone to then produce estrogen. Instead, we can kind of regulate that by giving just exogenous hormones. And so for some individuals that may be useful to help kind of regulate their levels of different hormones and kind of improve.

So for some people, they actually improve their acne and some individuals actually get worse. There's some nuance there. I'm not going to talk about all that here.

We'll get into that when we talk about OB-GYN stuff in the next semester, I believe. So we'll go into much more detail there. There are some situations where we could consider utilizing intralesional steroids. So these help more so with very strong inflammatory components here. So you could actually inject these into individual nodules.

While, you know, that could be all well and good. If you have like a lot of these nodules here, that could be very difficult from a logistical standpoint. So typically the smaller the number, the easier this will be to do. and you can see some systemic absorption. So we do worry about some adrenal suppression as a result.

I'm going to talk more about that in detail in just a little bit here. And then we can see some local tissue atrophy, so it could be some downside. Now, we could use oral corticosteroids, but we'd want to use fairly low doses as best we can in order to reduce overall this kind of high adrenal activity here. And in those patients having kind of like a bigger inflammatory flare-up, you could use maybe like a short course of like higher doses, and then as you start to reduce that inflammation, scale things back down. So typical oral corticosteroids we'd use include things like prednisone and dexamethasone just for representative examples there.

So questions, okay, those are the options. How are we going to kind of go through this? And I think going with a stepwise approach going from simplest to more invasive makes a lot of sense here.

So dealing with these kind of more minor types of acne, kind of the lower grade types here. We can see things like topical retinoids can be a very good choice here. So something like a tretinoin cream is totally fine.

You also consider benzoyl peroxide or salicylic acid. So you have a couple of options you can then consider. If they're not going to respond to that or it's much more severe, so you go to like a type 2, for example, here, this is where you get into using combination therapy. So if you notice topical retinoids plus benzoyl peroxide, topical or antibiotic there. So using clindamycin, erythromycin.

as a topical option may work at that point. If they're either not responding to this or you step it up to the type three, this is where we get into the systemic antibiotics. So you may still be using some of your topical products like your retinoids, depending on how they were working before. But now you'd want to introduce something like tetracycline.

So minocycline, doxycycline, any of those would be totally fine to utilize here, plus your typical topical therapy. What was working for them before, I'd say use it there. Also, you could consider, depending on overall hormonal activity, may consider something like oral contraceptive or something like a spironolactone.

That'd be something to consider there as well. And then... Once you have exhausted all of that, then we need to start consider utilizing something like isotretinoin.

That's kind of like the last line of defense. Once you've kind of exhausted everything else, now you get into the isotretinoin. And so again, just because logistically speaking, it's more difficult to get access to that medication because the side effects are so bad.

I don't want to reserve that to the very end or the very severe cases there. So that's kind of your step. So if I gave you a test question and said. You know, the patient says they've been taking benzoyl peroxide for, you know, a couple of months, but it's not really improving. Where would you want to go from there?

And so you probably say a topical retinoid. If I said, oh, they're using a topical retinoid plus benzoyl peroxide, where do you go from there? Oh, you know, say a topical antibiotic would work there, you know.

So kind of have an idea of kind of a step-by-step approach on how you might go along with that to say, okay, here's what the patient's responded to. Here's what they've maybe had bad experiences with in the past. What do you want to do next?

Those are always good questions to ask on a test there. All right. Next up, we're going to talk about dermatitis here. I'm kind of using this as sort of a launch point to talk about steroids more specifically. And we'll get into it.

So, again, we can see that atopical dermatitis is going to be a very common skin condition here. Eczema is another name for this. And what we're seeing is this kind of chronic inflammation. Caritis is a part of this and can be seen as part of this kind of atopic triad.

You may see asthma, allergic rana, conjunctivitis, along with atopic dermatitis. uh playing a role here and so um looking at this we can see that in terms of presentation there's kind of these major indicators and the minor indicators here which you know may not be as quite as indicative of eczema as some of the major indicators here but these are things we're looking for it's your family history of this you know um we have things like elevated ige levels etc right so our goals for these patients here that are so itchy and inflamed is reduce um provide symptomatic relief here if there's any specific triggers for them So things like allergy testing may be super useful for these patients here. Get rid of those if you can. And then try to prevent future exacerbations.

Try to prevent adverse reactions to treatment, which we're going to look at some of the strategies there in just a moment. And then treating the secondary skin infections. Because as patients get itchy, they're going to start to scratch. And then as you start to disrupt the skin barrier, now bacteria can get in and cause infections.

So if there is a secondary skin infection, we want to treat that too. So non-pharmacologically speaking, we can utilize things. And again, this happens a lot in kids. And so oftentimes they're more difficult to manage because of things like, you know, they're going to scratch. They're going to, you know, not really have a lot of control over that like adults might.

And so using things like, you know, lukewarm baths, keeping their fingernails short. Some cases using like a sedating and a histamine, like a Benadryl prior to bed can sometimes keep them asleep deep enough to where they're not going to start scratching. Distractions, remover tints, things like that all can be very useful.

And again, maintain good hydration, which makes me want to take a drink of water right now. So the reason why I use this as sort of a launching point to talk about steroids is because this is the gold standard for treatment here. And so the agent that we choose is based off of severity, location, things like that.

And so for our steroids, we're going to talk about them in terms of level of potency and go from low. to medium, to high, to ultra high. We're going to look at a few different ways we can differentiate these. And so low-potency steroids, these are more suitable for areas of thin skin.

So the face, intertrigenous areas, infants, for example. And these are better for long-term therapy because the lower the potency steroid you can be on, the less likely you are to run into systemic side effects. Okay?

So lower potency steroids are good for chronic long-term use. Medium potency can be used kind of for the rest of the body. And then if we have situations where we're having severe exacerbations, then we get into the medium to high potency types of corticosteroids. Note here that we'll go like, say, one to two weeks, and then we scale things back. So again, that ebb and flow, the waxing and waning of therapy, when you have the exacerbations, you'd step up therapy, and then as things die down, then you go back to your...

maintenance therapy which are going to be these more low to medium potency steroids here we'll see adverse effects are going to be typically systemic in nature as we're going to see here and one of the things you're going to see is that as more of those steroids start to penetrate through the skin and into the bloodstream you're going to see some pretty particular side effects and we've not had an opportunity to talk about this elsewhere like an ent or um you know ophthalmology but we'll talk about it here but basically you know locally you can see some issues you can see things like skin atrophy worsened acne potentially due to the you know um suppressant effects here uh dermatitis that could be related to the vehicle they're in but the systemic stuff is what i'm kind of more concerned about with these especially um higher potency steroids so one thing you can see adrenal suppression why do you get adrenal suppression Well, this is because when you apply exogenous steroids to the patient, the adrenal glands operate off of a negative feedback loop, right? So they're getting signals from the pituitary gland that tells them to produce steroids, corticosteroid, cortisol in particular, I should say. So when you apply exogenous steroids, you tell the hypothalamus and the pituitary, hey, there's enough steroids around here.

I'm not going to send that signal to the adrenal glands. I'm going to tell them they can take a break. And so if you're doing this chronically, either with like oral steroids, IV steroids, high potency topical steroids, the adrenal glands will get that signal to shut down and they'll stop producing cortisol because you're supplying exogenous steroids.

Well, if you were to say, for instance, stop taking the exogenous steroid cold turkey one day, the adrenal glands are not going to just turn back on like a light switch. They take time because you need time for the pituitary and the hypothalamus to detect. hey, we're losing steroids here.

Let's start to get the adrenal glands back online. It takes time. And so you could put the patient into a situation where they're having adrenal insufficiency. What happens then?

Well, they're not producing cortisol, so they cannot produce things like, they have a hard time regulating things like blood sugar. So they may get hypoglycemia. They may have problems regulating their blood pressure.

So they're getting hypotension. They can develop circulatory shock in some rare cases. So it can be very serious. So in those situations, You don't want to stop steroids cold turkey. You want to have sort of a taper built in.

Or in the situation here, you'd want to go from, say, a high potency and scale it back down to a medium or low potency. So that way they're always getting some degree of exposure. So generally speaking, when it comes to these more systemic actions of steroids, you want to go as low a dose in as short a time as possible to help reduce this.

Other problems you run into from the exposure to these steroids are extensions of the actions of what these steroids do anyway. So for example, they suppress the immune system. So you're more likely to have infections. They raise your blood sugar. They can raise your blood pressure.

You can see things like growth retardation in kids. So we want to try to avoid this as best we can by utilizing the lowest potency steroid possible for as short a time as we can. For some people that do require higher potencies, they may require longer treatment times, but we try to mitigate this as best we can. And we'll find a couple different ways we can do that. So...

There are several different charts that are out there. I'm going to show you a few of these. And my purpose is not to have you memorize each category and each drug that fits into this category. But here you can see they go from mild to moderate to potent to very potent.

Here's an even more detailed example here where there's two pages of this stuff. Notice there's so many of these. You go from super potent to potent to upper midstream, midstream, lower midstream, mild, least potent. Do I want you to memorize this list?

No, I do not. And at least no hydrocortisone is the very bottom, the least potent, just because it's the most common steroid you're going to run into, especially topically. What I do want you to know are four things, four things that can affect how potent a steroid is.

Okay, so let's look at those four things a little bit more detail. One of which is just the drug itself, just by its own nature, may be more potent than others. So for example, here you can see beta-methazone.

it's always going to be at the top of the list here. Because of its nature, it's going to be a more potent steroid, has easier time getting through the skin, can affect more of those systemic actions that we saw before, and sometimes may be necessary, may need something this strong. So the actual drug itself factors in.

Another thing that will factor in will be the strength of the product. So in some of these cases here, you'll see certain steroids will jump up or down. the list based off of the concentration.

So going from, say, a 0.1 to a 0.2 or 0.3 may be enough to go from a medium to a higher potency, or vice versa. So the concentration will matter. Because again, if I put more drug on the outside of the skin, that's going to draw more of it across.

You have a bigger concentration gradient, more of the drug's going to get through. So the drug itself, concentration gradient, but the dose we're giving will matter here. The next thing we'll factor in is going to be the salt form of the drug. So in some cases, you can find by changing the salt form, this can also affect potency as well.

Let's look at the example hydrocortisone. You notice here all the different versions. This is just the base hydrocortisone. If I change the salt form and I go to, say, for instance, the hydrocortisone butyrate or evalerate, this is now going to be more in your kind of mid-level kind of strength steroids here.

So concentration, the drug itself, the salt form can factor into the potency. And then the fourth thing is going to be the actual dosage form itself. So you will find that by going from something that is less occlusive to more occlusive, this can also bump something up in the potency charts.

So if you have something that is a cream that doesn't have as much occlusiveness as something like an ointment, that could bump it up. So if you're going to do it with a more occlusive type of dosage form, a vehicle, the more potent it's going to tend to be because the drug sits around for longer, sits there on the skin, is more easily able to cross over. There's more opportunity crossover, I should say.

Okay. So those are the four. Drug itself, salt form, concentration gradient, and the vehicle.

All four of those. So know how those will be affected if you change those. So I say, hey, if I'm going from, say, hydrocortisone base to a more lipophilic hydrocortisone butyrate, what does that do to potency potentially?

Oh, yeah, it increases potency. More of it's more easily able to get through. Or if I increase the concentration or if I increase the occlusiveness of the vehicle. Kind of have an idea of what that's going to do. If you go and work in Durham, you will figure out that, hey, you're going to have a stable of medications that you use.

It's probably not going to be every single one of these, but you'll probably have like five or ten. You'll be like, oh, yeah, for this type of patient, this is what I'm going to use. For this type of patient, this is what I'm going to use.

And so you'll kind of figure out your own kind of stable of meds you're going to use. Kind of like your team of Pokemon that you pick out. Like you'll have your team and you'll say, OK, for this situation, I'm going to bring out the Pikachu. This is what we're going to do here, right? You kids still play.

Pokemon, right? The Pokemans? No, I'm just kidding.

Other things we could do if steroids are not going to be sufficient or if we, otherwise patient cannot tolerate the steroids here, this is where you get into your topical immunomodulators. Immunomodulators just means that we're going to be suppressing the immune system to a degree. And so two drugs here we're going to have include tacrolimus and then pomecrolimus.

Again, these are topical versions of these drugs. You'll see tacrolimus as well being used systemically as a... immunosuppressant for things like transplant medicine for example but here we're using suppress immune system in the skin itself and while effective can also have secondary side effects so one of which can be pretty severe burning sensation patients may experience a lot of photosensitivity so you want them to be using high sps sunscreens to make sure to prevent you know risk for sunburns and things like that and we can see risk for cancers so certain cancers risk go up as you're utilizing these which makes them kind of second-lined if patients can otherwise not take topical steroids. Also, if patients already have a weakened immune system, this could then further weaken that just due to natural absorption of the drug itself from the skin. Other therapies, we could sometimes utilize oral corticosteroids to provide kind of like a nice burst or short course of higher dose steroids to the body.

And then we would want to use that for kind of providing more rapid relief. for severe cases here, but we would then want to taper down. So then taper back to whatever their topical steroids happen to be.

This could include prednisone, dexamethasone, methylprednisolone. Any of these are totally fine. Same side effects as what you would see with the topical steroids.

It's just these are more likely to cause those because they're being systemically administered. So I remember one time when my mom was in the hospital and she was having a bad pulmonary exacerbation. And so the nurse came in and she said, all right, got one drug to raise your blood sugar and one to lower it.

Well, the nurse was giving both a steroid, which is usually necessary for those types of pulmonary exacerbations, and then also insulin. And again, this is one of those examples of two drugs that counteract one another because the steroids are going to increase the blood sugar, and then the insulin is used to lower it back down. It's just a natural kind of fight that they'll have with one another. Okay.

Next, we have the other topical antibiotics we might be using. So these are agents we're going to mostly be seeing used for... First aid kind of purposes, you know, kind of general wound management here.

First of which is bacitracin, which is going to be another cell wall active kind of agent here. And it really is a large microbial range here in terms of coverage. Anything from strep to anaerobic, coxalide to tetanus, really, really effective here. Note, this was not in our list of systemic antibiotics.

This actually is really, really toxic. But fortunately, when applied to the skin, even to wounds, we don't really see any absorption. There's no systemic toxicity to worry about.

We just would never want to use this systemically there. You can either find this by itself as just straight bacitracin, or you may see it used in combination to some people call either double or triple antibiotic. And so it may include things like neomycin, polymyxin B, which I'll get into in just a second. Adverse effects wise, the biggest thing these causes may be some allergic dermatitis, but that's pretty rare for the most part. Another one here is mupiricin.

This is going to be used to disrupt protein synthesis, in particular in MRSA. And so where we use this most frequently is to eliminate nasal carriage of staph aureus. So if you were to come into the hospital, for example, they may do a nasal check to see if you're harboring staph aureus.

And you can use Bactroban or mupiricin to basically eliminate that sort of carrying of the staph itself. Not absorbed, so no systemic concerns there. However, it can cause some mucous membrane irritation.

due to the vehicle that you're using there so that could be one common side effect you run into next up is polymix and b this one is really good for treating a lot of gram-negative types of organisms here um here with this one you do want to be cautious if you were to have really um large open wounds or like denuded skin so i think about like motorcycle accidents or people are kind of like dragged on the ground they can have huge areas of denuded skin you would want to be cautious using polymix and b just because of the amount you're going to use because there could be Some risk for absorption, which can lead to things like neuro or nephrotoxicity. So in those instances, using just a straight bacitracin may be a better option for those patients. But if it's like a typical NIC, cut, laceration, whatever, polymyxin B is going to be totally fine there. And then we have some of our aminoglycosides, things like neomycin and occasionally gentamicin.

Remember, these are going to be protein synthesis inhibitors here. Good for treating a lot of gram-negative infections. Here, if they have, again, very large open wounds or huge areas of denuded skin, can see some systemic accumulation, but it's pretty rare you're going to run into that problem there. One thing to note here, if you're going to see skin sensitization, it's probably going to be due to neomycin. So, for example, if someone were to have an allergic reaction to triple antibiotic ointment that had polymyxin B, neomycin, and bacitracin in it, chances are they had the reaction to the neomycin.

So in that situation, I would just switch them over, just using single bacitracin, and you're good to go from that standpoint. I know I have a couple of topical antifungals here we can see. Here we have the azole, antifungals, clotrimazole, ketoconazole, et cetera.

These can be used for vaginal uses, for topical uses. Keep in mind, treatment times, as we mentioned before, are longer than bacterial infections, just because of the slow-growing nature of the fungus itself. This might be like a two-or three-week kind of treatment time versus... like a seven to 10 day.

It just kind of depends on the type of infection. Fortunately, a lot of like the vaginal infection can be treated with like a one day course or a three day, seven day course, just depending on the product that you're using there. For topical uses here, you sometimes may see these being used as corticosteroids. Those are just being used to help reduce the overall either symptom irritation. The isolated fungals, it's actually gonna be treating the actual infection itself.

Here's one example of one called Slythelopirox. This is actually a nail lacquer, so it's called Pinlac. And so you can apply this to the nail like you would like a nail polish, and you can help to treat these kind of nail-based infections.

Keep in mind that because of the long treatment times, people often are not going to be compliant with this, meaning it's going to be less effective. Or, you know, some nail infections with fungus take up to like a year to treat, and patients may start to see improvements and be like, okay, well, I'm cured. Stop using the product, and then it comes right back. The benefit with Penlac is the fact that it's a lacquer. It stays around for quite a bit.

So this is about as occlusive as you can get as you apply it to the nail. It kind of dries on there and just kind of keeps working. So it can be useful from like a compliance standpoint for patients to kind of keep with it and use it regularly.

We have things like naphthene, terbinephine. These are going to be good for treating things like an athlete's foot and other types of tinea type of infections. There again, side effects are mostly just local irritation.

So nothing big to worry about from that standpoint. And then we also have things like nystatin. We talked about nystatin before as being utilized orally and being nice because you could treat things like thrush, for example, because it does not get absorbed systemically.

When used topically, it's good for other types of candida infections. So, you know, candida infections like diaper rash, for example. We would actually use nystatin, the powder, around patients who would have like stomas like G-tubes and things like that because it was able to prevent infection due to fungal.

causes as a result of that so it could be another useful there a use for it there and then finally there's a couple topical antivirals we have here one which is going to be acyclovir pencyclovir has been used as well mentioned these before same mechanism of action working as sort of a guanine analog that the virus cannot then add other nucleotides to to disrupt dna production here and is good against herpes virus and so again good if you did want to use systemic acyclovir for whatever reason you can utilize this topically and have reduction in overall symptom time remember earlier use the better as soon as they start getting symptoms start applying it early to help improve its overall efficacy there And final one here, miquimod is going to be utilized for managing things like certain types of warts and also certain types of cancers like a basal cell carcinoma. So this one's interesting because it actually stimulates the immune system. It actually helps to stimulate macrophages, to produce more TNF-alpha and interleukins.

And so skin irritation is almost universal for these patients. And actually, that's a good thing because it's stimulating the immune system to fight off that particular infection, whether it be virus, due to... causing a ward or something like that. And so the more inflammation you get, these edema and there's erosions, ulcers actually means it's being more effective.

However, that could be to the point where patients don't want to keep taking it because it's so uncomfortable. But again, the other way, the pros and cons, you know, in terms of what we're treating there. And then I'll do it for dermatologists, kind of majority of topics here. No, I don't, we blocked off three hours. I'm not really confident that I could even do three hours talking about.

dermatology put a gun to my head but that is the majority of it is there any questions or anything i can answer for you at this particular time if not you're free to go bye con dios hoping like somebody like my closeted like derm people come out but ask a little questions that they're curious about i don't see anything here so far and look at that now that whatever magic i performed i dropped zero frames this is actually a very successful stream by all accounts so okay for that hopefully my luck will continue as we go forward all right no questions at all All right, well, you guys have a good one. Thanks so much for joining me. I appreciate you all.

I think we meet later this week. Is that the case? Yeah, so Thursday, I'll be talking to you guys about something I can wax on for about three hours for, most likely.

It'll be the autonomic nervous system. So get ready for that. It's going to be a fun one. If you have any questions in the meantime, let me know. Otherwise, I will talk to you soon.

Have a good one. Bye.