 Hey everybody, Dr. O here. This is going to be the first video in quite a long series where I'm going to cover the different types and classes of antibiotics. This is not a pharmacology class. I'm not going to cover all the details of every brand name, but we're going to focus on the major classes of antibiotics and I'll certainly give you examples. We're going to start here with the group of antibiotics called the beta-lactam. So this video specifically is going to be about penicillin, the natural penicillin and the semi-synthetic penicillins, but I'll do a separate video on cephalosporin and in a separate video where I cover both monobactam and carbapenems together. So they're all very significant. Hopefully you can see from this top image why they're similar because they all have the same beta-lactam ring, which some people would call the nucleus. So they have the same nucleus or they have the same beta-lactam structure. The difference is they're going to be primarily where you see the R's. The R groups, the slight changes in these R groups make these antibiotics different, which is some can survive the trip through the stomach, can be taken worldly. Others are going to have extended spectrum. Others are going to resist some of the resistance factors that bacteria have come up with. So the fact that they're similar is important, but their differences are primarily why they all exist. The other problem though is the fact that they're also similar means that some microbes have evolved the resistance to combat all of these. So if you develop an enzyme like penicillinase or more often called beta-lactamase, it doesn't mean that you're just penicillin-resistant. You would also be resistant to the rest of the group. So the similarities are kind of a problem too when you look at it from an evolutionary standpoint. How these work, the reason I have these all clustered together, is these are going to be your cell wall inhibitors. So they inhibit the production of cell wall. So the first thing you should think of whenever you think of a cell wall inhibitor is, number one, these are going to be way more effective against gram-positive bacteria, typically, than gram-negative. And that's because gram-positive bacteria, their big thick cell wall, is their primary defense. Gram-negative bacteria have an outer membrane outside of their cell wall, so they're not as concerned. So some of these certainly are effective against gram-negatives. I'm not saying that, but the first thing you think of is they're going to be a bigger effect on gram-positive. So here I just have a quick picture of what the peptidoglycan cell wall looks like. It's called that because you've got glycan. You have these carbohydrate backbones. That'd be the blue and orange structures there being held together by proteins. So most of these antibiotics are going to inhibit something called penicillin binding protein, which is a trans-peptidase, but they're going to inhibit the connecting, the cross-linking of these peptidogly, these carbohydrate backbones, which means you're going to have very weak cell walls. So again, I won't go through all this detail in the separate videos on this topic. These are usually going to be bacterial, they are going to be bactericidal. So you think about every time there's a new generation of bacteria, they're going to have a weaker and weaker cell wall until they reach the point where they either, it's so weak that they disrupt your or it disappears completely. So give after a few generations, this will be fatal to these microbes, bactericidal. All right, let's go ahead and jump in. So we're going to focus on all these groups here. It's going to be a little bit longer video, but bear with me. Super, super important in microbiology to understand antibiotics. So the first two we have are the natural penicillin. So these would be the ones that we actually found from the penicillium, you know, from the fungus, from the penicillium mold. They believe it was penicillium chrysogenum would be where they found this. Interesting story, they were looking, when they first found penicillin, they couldn't find strong enough strains that would produce enough of a potent antibiotic. So they put out a call for, you know, if you have anything that has a green or blue mold, like, you know, bring it to us, let's take a look at it. And the story, the legend is anyways, that a moldy cantaloupe is where the penicillium came from that was powerful enough and potent enough to make the antibiotic penicillin. So that's just kind of an interesting thing. It was first discovered in 1928, commercially used in 44. I covered the history back in a separate video. So the natural penicillins are the ones produced by these microbes. So penicillin G versus V, here's how I remember them. G comes before V in the alphabet, oral comes, or injection I comes before O, right? So penicillin G has to be injected. So G comes before V, I comes before O. Penicillin V can be taken orally. So that's going to be the key difference here. Penicillin G is primarily effective against gram-positive bacteria, small handful of gram negatives, but must be injected. Penicillin V, that slight change you see there with the R group with the addition of the oxygen, makes it more stable in stomach acid so it can be taken orally. So those are your two natural penicillins, penicillin G versus penicillin V. Let's move on then to more changes to the R group. You see, adding the amino group to the R group of ampicillin and amoxicillin created a semi-synthetic penicillin, which means you start with that natural penicillin and then make some changes to it. And now it's semi-synthetic. So part natural, part synthetic. So these are called the amino penicillins, ampicillin and amoxicillin. And what that primarily does is it made them extended spectrum, which means they still kill gram-positive bacteria, but they can kill more gram-negative bacteria than regular penicillin can. So that makes ampicillin and amoxicillin extended spectrum. But hopefully you'll see, you know, looking at these R groups, again, these side groups, you see one more change. Amoxicillin has the hydroxyl group added to it. And what that does is it makes it more stable in acid, which means it's going to have better oral absorption. So you can take ampicillin orally, but amoxicillin will be better absorbed. All right. So that's going to be the amino penicillins, ampicillin and amoxicillin. I do want to talk about one more that's not shown here, and that would be augmentin. So if you take amoxicillin, which is really the top of the line, you know, semi-synthetic penicillin, as far as we've talked about so far, you add one more compound to it. I like to call it potassium clavulinate. It's a hard one to say. Some would call it clavulinic acid. But what that does is it's actually a penicillinase inhibitor. So we mentioned, let me go back. We mentioned that penicillinases or beta-lactamases are going to be enzymes that some bacteria develop. Think of them like molecular scissors that go in and chop this beta-lactam ring. Well, our solution has been to create antibiotics that are that are penicillinase resistant. So that's what I would say augmentin is really the top of the line cell wall inhibitor, in my opinion. All right. And then the last group here, before we're done with this video, is going to be methicillin. So you've probably heard of methicillin. If you haven't, you've heard of MRSA, which is methicillin-resistant staphylococcus aureus. So methicillin, they totally change the side group. As you can see here, this is a dimethoxyphenol group or something like that. It's not important. But the wild change to the side group is what made this the first penicillinase-resistant penicillinase. So it made it resistant to this beta-lactamase enzyme that was trying to chop up these drugs. The problem is, of course, that we're trying to fight an evolutionary arms race, an evolutionary arms race, with microbes that are better at it than us. So we released penicillin. They came back with penicillinase resistance, or penicillin resistance. So we used methicillin and they developed methicillin resistance. So that's why methicillin is not even used anymore. It's been discontinued because there's just been too much evolution around it. Our next response would have been oxacillin, another antibiotic that's not on here, but it's another semi-synthetic penicillin that did replace methicillin in clinical practice because methicillin became worthless. And then we'll do other videos about vancomycin and some of those responses. So oh, you think methicillin isn't strong enough? Well, let's use vancomycin and then we'll wash your hands of it. Well, no, because use of vancomycin created Versa and VISA and VRE. So the microbes are going to continue to evolve around our antibiotics, just how evolution works. So all right, so these are going to be your natural and semi-synthetic penicillins. So watch for the other videos where I cover different cell wall inhibitors and then I'm going to go through all the other types of antibiotics as well. So I truly hope these help. Have a wonderful day. Be blessed.