Transcript for:
Overview of Beta-lactam and Penicillin

Crush it. Hey everybody, Dr. O here. I am gonna, this is gonna be the first video in quite a long series. Where I am going to cover the different types and classes of antibiotics, so this is not a pharmacology class. I am not going to cover all the details of every brand name, what we are going to focus on the major classes of antibiotics, and I will certainly give you examples. Uh, er, we are going to start here with with the group of antibiotics called the beta-lactam. So, this video specifically is going to be about penicillin and the natural penicillin and the semisynthetic penicillins. But we will do a separate video on cephalosporin and a separate video where I cover ____________ and carbapenem’s together, so, they are all significant. Hopefully, you can see from this top image why they are uh, similar because they all have the same beta-lactam ring which some people would have called the nucleus. So, they have the same nucleus, or they have the same beta-lactam structure. The differences are going to be primarily where you see the “R’s”. The “R” groups the slight changes in these “R” groups are what make these antibiotics different which is uh, some can be uh, some can survive the trip through the stomach and be absorbed uh, be taken orally, others are going to have extended spectrum, others are going to uh, um, resist some of the resistance factors that bacteria have come up with. So, the fact that they are similar is important but their differences is primarily is why they all exist. The other problem though is the fact that they are all so similar means that some microbes have evolved the resistance to combat all these. So, if you develop a, if you become, 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, er, resistant to the rest of the group. So, the similarities are kind of a problem too when you look at 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. That’s because gram-positive bacteria there big, thick cell wall is their primary defense. Gram-negative bacteria have an outer membrane outside of their cell wall, so they are not as concerned. So, some of these certainly are effective against gram-negative. I am not saying that but the first thing you think of is they, uh, they, uh, are going to be bigger uh, more, uh, bigger effective gram-positives. See, here I have a quick picture of what they peptidoglycan wall looks like it’s called that because you got glycan you have these carbohydrate back bones that would 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 transpeptidase, but they are going to inhibit the connecting cross linking of the peptidoglycan, uh, these carbohydrate back bones. Which means you’re going to have very weak uh, cell walls. So, again I won’t go through all these detail in the separate videos on this topic. These are uh, usually going to be bacterio, uh, they are going to be bactericidal. So, uh, you think about uh, every time there is uh, a new generation of bacteria. They are going to a have a weaker and weaker cell wall until they reach the point where they are so weak that they rupture, or they disappear completely. So, give, after a few generations this will be fatal to these microbes bactericidal. Alright, let’s go ahead and jump in, so we are going to focus on all these groups here it’s going to be a bit longer video. But, bare with me super, super important in microbiology to understand antibiotics. So, the first two we have the natural penicillin’s these would be the ones that we actually found from the penicillium, you know, from the fungus from the penicillium mold, its uh, they believed it was penicillin chrysogenum would be would be where they found this. Interesting story they were looking when they were first found penicillin, they couldn’t find strong enough strains that would produce enough of, of, er, a potent antibiotic so they put a call out for if you have have anything that has a green or blue mold like bring it to us, let’s take a look at it. And the story the legend is anyway a moldy cantaloupe is where the penicillin, penicillium came from that was powerful enough, and potent enough to make the antibiotic penicillin. So, it’s just an interesting thing uh it was first discovered in 1928, commercially used in 44, I covered the history back in separate videos. So, the, the natural penicillins are the ones produced by these microbes. So, a penicillin G verse V here is how I remember them, “G” comes before “V” in the alphabet, um, oral comes before er, er, er, ah, ah, ah injection “I” comes before “O”, so penicillin G needs to be injected. “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 hand of gram-negatives, but must be injected. Penicillin V that slight change of that you see in the “R” group with the addition of oxygen makes it more stable in stomach acid. So, it can be taken orally so those are your two natural penicillins. Penicillin G verse Penicillin V. Let’s move onto then uh, ah, more changes to the “R” group you see adding the amino group to the “R” group of the ampicillin and amoxicillin um, created a semisynthetic penicillin which means you start with that natural penicillin and then make changes to it. And now its semisynthetic so part natural and part synthetic. So, there are called the amnio penicillins ampicillin and amoxicillin and what that primarily does is that it made extended spectrum which means they still killed gram-positive, 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 looking at these “R” groups again and these side groups you see one more change amoxicillin has the hydroxyl group added to it. And what that does it, uhh, err, 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. Alright, so that’s going to be uh the aminopenicillins, ampicillin and the amoxicillin. I do want to talk about one more that is not shown here that would be Augmentin. So, if you take amoxicillin which is really the top-of-the-line semisynthetic penicillin as far as we have talked about so far. You add one more compound to it, I like to call it potassium clavulanate it’s a hard one to say um some would call it clavulanate acid but what that does it actually penicillinase inhibitor, so we mentioned let me go back. We mentioned that penicillinase is beta-lactamase are going to be enzymes that some bacteria develop think of them as molecular scissors they 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 um, cell wall inhibitor in my opinion. Alright, and the last group here before we are done with this video is going to be methicillin, so you’ve probably heard of methicillin and if you haven’t you have heard of MRSA which is methicillin-resistant staphylococcus aureus so methicillin totally changes the side group as you can see here. this is a uh, side group or something like that, uh, it’s not important. But the, the, wild change to the side group is what created made this the first penicillinase resistant penicillin, er, 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 are trying to fight an evolutionary arms race, an evolutionary arms race with microbes that are better at it then us. So, we, so we, um, we release penicillin they came back with penicillinase resistance er, penicillin resistance uh so we use methicillin and they and they develop methicillin resistance so that’s why methicillin is not even used anymore it’s been discontinued because there has been too much evolutionary around it. Um, our next response would’ve been oxicillin another antibiotic that is not on here. But it’s another semisynthetic penicillin that did replace methicillin in clinical practice because uh, methicillin became worthless. And then, and then we will we uh, we will do other videos about vancomycin and some of those responses, so, oh you think methicillin isn’t strong enough let’s use vancomycin and then we will wash our hands of it. We will know because uh, um the use of vancomycin created VRSA and VISA and VRE’s, so the microbes are going to continue to evolve around our antibiotics that’s just how evolution works so, alright these are going to be your natural and semisynthetic penicillin’s so watch for the other videos. Where I cover other cell wall inhibitors and then I’m going to go through all the other types of antibiotics as well. I truly hope these help, have a wonderful day, be blessed.