Fungal Skin Infections Medications: Mechanism of Action (Nursing)

00:00 Now, let's connect the pathophysiology to how our medications work. Now to kill fungi, we don't want to harm the cells, human cells, but we want to kill that fungi, so we need a target. We look at the differences between the fungal and the human cells. One major difference is the cell membrane structure. So fungal cell membranes contain a unique sterol. It's called ergosterol. Now this ergosterol serves a similar function to cholesterol in human cell membranes. The unique difference between the fungal cells and the human cells makes ergosterol an excellent target for antifungal medications. Now let's talk about some topical azoles. The azole antifungals, these are medications that end in A-Z-O-L-E like in names you'll see there like quatrimazole, myconazole, and ketoconazole. These are medications that will target ergosterol synthesis. Now when you target the synthesis of ergosterol, we're going to have less of it and that is bad news for the fungal cells. Because these medications specifically block an enzyme called 14-alpha dimethylase, they need that 14-alpha dimethylase to convert a precursor molecule into ergosterol. So in case that is a lot of words that are spinning around in your head, what these medications do is they block the process of converting a precursor of ergosterol into ergosterol. So that's going to attack what the fungus needs in order to live. Now, if a medication prevents the synthesis of a key membrane component, what do you think happens to the fungal cell? Pause and see if you can answer it.

01:42 Well if you said the cell membrane loses its integrity, and then it has increased permeability, then the cell contents leak out, and outside substances leak in and ultimately the fungal cell dies. You were exactly right. I'm going to enter this disclaimer before we talk about this next group of drugs, because there's a lot of controversy about how exactly these are pronounced. We did our best, we did our research. If you disagree with us just let us know. But the group is allylamines. Okay, now allylamines like terbinofene and naphthofine, these also target the ergosterol synthesis, but it's in an earlier step in the pathway. So allylamines inhibit an enzyme that's called squalene epoxidase. I know that is a lot of strange words, but the important takeaway point is that you keep in mind these drugs work at different points of the process. Think of it this way. Imagine a manufacturing assembly line for ergosterol. Now azoles block one of the last steps in the manufacturing line, but allylamines block an earlier step. So here's why this is so cool. This not only prevents ergosterol production but will also cause a toxic buildup of that substance we talked about, squalene. Now, this will build up inside the fungal cell and kind of get this double whammy effect to take that fungal cell out. So that's why medications like terbinofene are often more effective against certain fungi, particularly those causing nail infections because they have both a fungistatic effect, meaning it stops growth, and a fungicidal effect which actually kills the organism. Now there's several other agents that work through various mechanisms. We're going to take a look at four other topical agents. Butenafine works similarly to the allylamines. Now, keep in mind that picture we have of that manufacturing center. Cycloperox disrupts the cell membrane transport and inhibits metal dependent enzymes. Tolnafdate disrupts the hyphal growth. I know that's a weird sounding word, but hyphal growth is the extension of the fungal bodies as they're spreading. So this medication will disrupt that growth and the cell membrane function. And finally, Amorolfine inhibits two different enzymes in your gastro pathway. Now there's an important clinical point that I want to bring up because sometimes, people have a consistent misunderstanding about this. Nystatin is something that you might be familiar with for treating oral thrush. I want you to keep in mind this is not effective against dermatophytes. It works completely differently. See a nystatin it binds directly to the existing ergosterol rather than preventing its synthesis, and it's only effective against Candida species. This is critical that you remember that when you're selecting and evaluating treatments.