Transcript for:
Pharmacodynamics L7

e hey everyone how's it going um let me know if you can hear me okay I'm concerned about my internet connection I might need to restart my stuff if the stream is not looking good okay so you can hear me how's it look screen is good too okay I'll take your your word for it um welcome back it's 3:00 me just make sure I'm recording just uh just in case anything bad happens again like last time let's good thank you Jenna Peron I appreciate you both uh welcome back this is our last pharmacode Dynamics session together so we're doing our uh antibiotics review or introduction to antibiotics I should say not really reviewing it for seeing it for the first time um and the reason why they do this lecture early is because they want to make sure they kind of put it in the end of pharmacodynamics is in order to at least get your beaks wet a little bit just in order to uh have a little bit of exposure to antibiotics just because it is something that you're going to be touching on basically every aspect of medicine and so no matter where you go you're probably going to be dealing with some amount of antibiotics so Le want to cover it here get you started and then we can hit the ground running off for Farm one in the fall there which will be here before we know it as it turns out um okay so here's some instructional objectives we're going to be covering here and first I want to start off with the kind of a bit of a review on microbiology itself just to make sure on the same page when we're discussing um kind of our antibiotic lingo as we get into it here so the first thing we can um have to figure out okay well if a patient has an infection one you want to know where it's at but you also want to know what kind of bugs are there right because um as we'll find that depending on the type of infection you're dealing with whether it's so titis media menitis pneumonia cellulitis there's kind of a general spectrum of bacteria that are more or less likely to be present there and that often times will dictate what type of antibiotic that we use in order to treat those patients there are of course exceptions to the rule but generally speaking we need to understand how to classify these different organisms and then which ones kind of fit into the category so the first Broadway that we categorize our bacteria gram positive versus gram negative h delineation there between two big groups of bacteria and that's important because um if you tell me for instance you did sputum culture on a patient you suspect has pneumonia it's a gram positive coxy and clusters that tells you something very different than if you saw gram negative basili for example and so that's one of the first determinant we can get we don't even have to have a whole culture perform we can just have microscopic review and do the Gram stain to determine whether it's going to be gram positive versus gram negative and that's going to be one of the big things um or one of the big decision points on what type of antibiotic might be necessary because what we're going to find is is that every antibiotic only has a certain spectrum of bacteria that it treats so something that's really good at treating gram positives may have awful time treating gram negatives and vice versa in other cases you can have what we call very broad spectrum antibiotics meaning they treat a ton of different types of bacteria some are narrow Spectrum some are broad spectrum and they each have their place in medicine and when we're going to be employing these antibiotics in different clinical situations so generally speaking when we're thinking about our gr positive bacteria here we start for the gr positive coxide the big ones that we're going to be encountering here will include bacteria like our staf orus this is a big one because staff orus usually comes in one of two flavors you have your mssa which stands for methylin sensitive storus or you have MSA which is methylin resistant if you had to guess you can see methylin is an older antibiotic we used to use don't actually use it anymore but the name stuck and so it indicates whether the strain of Staff ORS you're dealing with is sensitive to that particular drug or resistant that's another big decision point if you think it's Mera you may have to use different antibiotics and if you thought it was mssa for example there that's a big one you're going to encounter there for a lot of like upper respiratory stuff you're going to see a lot of strap num numo for example um on the skin where's lot of grand positive bacteria so that's just staff up dermus for example and then in the GI track you can see organisms like your inner cacus so these are some of the co common sort of bacter you're going to be running into when it comes to treatment for different types of infections um you also want to be considering whether your antibiotics are going to be working against aerobic organisms or anerobic organisms because again those will cause different types of infections and may require different antibiotics so for example when we think about claustrum diffys seals that causes C diff infections that requires a different type of antibiotic than say an mssa infection for example and so you want to know what you're dealing with in order to know what kind of antibiotic you use to treat that um in the mouth for example we have a lot of gram positive Anor robes like peptostreptococcus and things like that cluster profin and so if you're suspect you have an anerobic infection again that will dictate what type of antibiotic you're going to be using there then you get into your Grim negative basil are super super common especially in things like urinary tract infections a lot of infections in the elderly would be caused by this gam negative basili um you have your Ina for example here this is where you get into stuff like Eola ecps Proteus salmonella for example here one notable anob out of this group here would be Boris fragilis that'll come up occasionally and then you get into the really scary stuff here so you get into things like ponus renosa asabor these can be a source for really resistant especially um Hospital chir infections you get these really resistant bugs like pseudomonas that can be really problematic in terms of which antibiotics we have available to even treat that um other stuff you can see come up include bugs you might find in like the upper respiratory tract things like hemophilus influenza more exy cyalis bugs like that and then even things like gorea can be found here as well and then out of the third group so you have your G positive G negative and then we talked about aerobes and anoes OB anes don't need oxygen um and then we have also what we consider to be our atypical path pathogens and so these are bugs that are they're resistant to the gram staining process they don't really fit into one category or the other and so we call them atypical as a result of that and so this includes things like your chlamidia species uh Legionella pneumonia micoplasma pneumonia U as you can tell you find a lot of these for like lung infections for example like pneumonias um so those will come up pretty commonly there as well so based off the kind of the common bacteria you're going to run into um you can basically see that for different sites for infection you'll get a general idea or a general feel for the type of bacteria that are likely to be there so for example if I'm dealing with the skin and soft tissue infection well what do you kind of notice on those common players here well staff and uh step epidermus and streptococus it's a lot of grand positive bacteria which makes sense because we have a lot of grand positive Flora on her skin anyway so if you were to have an injury or cut or something like that it gets infected what's it going to be infected by well change are it's when be Grant positives does that mean that it's always caused by those no but if you are treating someone empirically what does that term mean empirically well it basically means that you are um starting with your best guess because maybe you don't have cultures available cultures take a while to come back I'll talk about those later um and so you have a a patient you say yes I think it's this infection and then based off the odds these are the most likely bugs here so I think based off of that my best chances to cover that would be to use this drug that's called empiric treatment and so you want your first best guess to be correct more often than not and so this is why we cover for these more common bugs here uh if you notice for things like Bone and Joint which are kind of adjacent to the skin and soft tissues here you notice still there's a lot of gr positive bugs that are present however notice you can still get some odd things showing up here so for example if you were to have say like a decubitus ulcer I say bedbound and they get a decubitus ulcer that's on the sacrum for example there well you know it's pretty close to the rectum you could see possibly the gram negative rods or gr negative bugs that normally live in the gut could be present there so there are always exceptions to the rules for sure but again these are the things we consider to be kind of most commonly present we want to cover for these um you know things like menitis for example often times you need to look at the patient risk factors to see what things they may be more prone to um so for example very young children when they're first born don't have a very good immune system and so they can may be more susceptible to things like leria species causing menitis versus someone who say is an adult or teenager has a more competent immune system so the point is not to memorize all these bugs here based off the infection but I just want to give you a general sense for like okay well you know based off the type of infection there's going to be a likely set of organisms present and that then informs why I use this particular antibiotic I don't want you just to memorize when we get to it they like okay o tius media we're going to use moxacin but like why do we use moxacin well it's because of the likely bacteria that are present based off the coverage based on the type of infection is that informs what coverage we need for our antibiotics here um for the abdomen uh and abdominal infections like if we have someone who uh for example has like a ruptured appendicitis that can be really bad um you'll notice there's kind of two main flavors of bacterior that show up a lot of gram negative bugs like eoli and Proteus and Kella but then you also get into stuff like couple Gros like inter caucus we also get into things like bides which is an anoro so now I need to also consider not just coverage for a lot of these gram negative bugs but now I need to consider coverage for Anor robes as well and that may require in some cases use combinations of drugs where One Drug provides coverage for these bugs but to hedge my bets I'm going to include the second drug in order to treat these other bugs that could be present and then you can make decisions on down the road once you get cultures back in order to have to streamline things um UTI you're going to see a lot of gram negatives there however there can be cases where gr positive get mixed in so for example someone has a chronic catheter in place one thing you learn is anytime someone has Hardware in place that can include IV lines you know VP shuns um you know catheter urinary catheters IND draal tubes these are all great vectors for bacteria to get into the system where they might not have done so otherwise and so this is why we always have um strong pushes to hey do we need this IV still if not get rid of it do we still need to have this urinary catheter in place if no get rid of it right because that helps to eliminate potential source for infection uh mouth infe you see a lot of gram negative or I'm sorry anob coverage that we need to have there so for example if someone gets into a bar fight and one person bites the other person that could be a source for infection in which case we need need to make sure we're covering for those anti robes that are likely present in the mouth along with whatever is on the skin that could have and then introduced into that wound for example there uh in some cases you may find that the spectrum of bacteria can change based off of where the infection happened at so for example if you're looking at lower respiratory tract infections like pneumonia for example you have things like community acquired pneumonias but then you have nosocomial pneumonias nosocomial means that they picked it up from a health care setting so either the patient was in the nursing home or maybe they came in for to the hospital for a surgery and then they get this like secondary infection that happens it's a nosocomial infection um and if you kind of look at the list here you can see that the more likely to be present bacteria for the nosocomial stuff is always scarier and always more likely to be resistant than your community quired things so like you know H influenza strep pneumonia Legion we can treat that that's relatively easy but you come in with a Mera infection pseud amonous these can be pretty nasty bucks bus meaning treatment time may be longer you're using antibiotics with like a bigger spectrum of activity potentially and so all this kind of factors into okay well if I have someone who's walking off the street I diagnos with pneumonia I me choose an antibiotic you know a for them but someone who's coming from the nursing home they may require a totally different set of antibio antibiotics just to make sure recovering for the correct bugs that are there and as you practice you'll get a sense for okay when patients have this type of infections it's probably likely to be this type of organism boom I want to use this particular drug and so you get a general sense for that as time goes on so how do we determine whether or not a drug is going to be effective at being able to treat a given infection and we can do this in a couple of different ways since I'll talk about cultures and sensitivities in a second here one really helpful thing that you could use um that will be developed basically every hospital system you go to this is something called an antibiogram and so these are really helpful because basically when you send off a culture whether it be urine culture blood culture sputum culture whatever the case may be that all gets collected in the lab and they will keep a record of what grows in the sample and then they will subject it to sensitivity testing what that means is they will basically expose that bacteria to different types of antibiotics to see whether it is susceptible meaning it kills the bacteria it is intermediate which means kind of in between or if it's resistant meaning the antibiotic just did not work very well to kill off that bacteria and based off the number of different samples they're going to collect they can get a pretty good picture of sort of the local environment and what resistance rates look like within a community so this one in particular came from the St Ian's Hospital in main doesn't really matter how old it is but these are still things that are developed every hospital system you go to so for example here this BAS basically will tell you one the bug that they were looking at tell the number of isolates they have so you can kind of get an idea for the just the general prevalence of these bacteria in the samples that were collected here so for example you see a ton eoli that's just natural because again you get a lot your tract infections things like that so you're going to see a lot of that versus some things which are more rare so for example having pomonis was much more rare than an eoli sample so that's interesting but then it also will tell basically the percentage of samples that were susceptible to that particular antibiotic so you notice antibiotics listed across the top here so if I was going to treat my patient for an presumed ecoli infection would I want to use something that only has maybe like a 65% chance to kill it or do I want to use something that maybe has say a 96 or maybe 100% chance to kill it that could be something you have to consider when choosing what type of antibiotic to use there are other considerations we're going to get into but these are nice because they'll basically show you within this environment this particular one in Maine wher happen to be working um what the local infection patterns look like and what the local resistance patterns look like such that if you were to take this antibiogram and then go to somewhere like California none of this may hold up it may be completely different because resistance patterns will change geographically they can change over time too so this thing from 07 is probably no good anymore probably is not going to be all that consistent with what you might find today because again one of the big things we're fighting here is resistance to antibiotics because there's not a whole ton of new antibiotics coming out but the bacteria keep getting better fighting them and being resistant to them so these are useful tool now how do they even determine whether something is going to be effective against a particular bacteria and so this is where you get into your cultures and sensitivities culture meaning we took a sample from the patient we wiped it on this augur plate and we grew out the bacteria so that way one you can get identification what it is and then you can subject it to the sensitivity testing and so basically what this is you'll drop these little discs here into the petri dish and based off of what we call the zone of inhibition this is the area around which no bacteria are growing and depending on the size of the zone of inhibition we give you a sense for how good that drug is at killing that bacteria because the concentration is going to going to be highest obviously where the disc is cuz the drug is that's where it's originating from and then it will diffuse out in a circular Direction such that the lower concentrations here may not be good enough to kill the bacteria but as you get closer and closer concentration gets higher then you notice no bacteria growing So based off the size of zone of inhibition can give you a sense for how good did this antibiotic kill the bug so if I were to look at something like this particular one here for example there's not much of a zone of inhibition this one is probably going to be resistant or this bacteria sample sample is resistant to this particular antibiotic versus something like this drug here or this drug here get much better sensitivity because you can see that it has pretty good job of preventing that bacteria from growing so that's good so you can see and you'll get a report back from the lab it usually takes two or three days or so for most um aerobic bacterial cultures and sensitivities after about two or three days the lab will send you back a sheet basically this says hey here's what grew here's what it was sensitive to here's what it was intermediate to and here's what it was resistant to and generally speaking When selecting antibiotic you always want to go with whatever is susceptible intermediate or resistant no good just not going to work very well for your patient there uh another way you could do this would be what's called an e test and so basically is a strip here they'll have various concentrations of a given antibiotic here so the highest concentration at the top and get progressively smaller and this will tell you specifically what concentrations do we start to see the inhibition actually start so obviously the higher the concentration the bigger zone of inhibition just because there's more drug there and so again these are useful tests to be able to tell us whether something happens to be susceptible intermediate or resistant to a drug so looking at this and again tell me if the video is not working out so well I think I don't know why it's being picity maybe I need to restart something I don't know anyway so controlling resistance this is the big problem we run into um we do not want to make decisions about what antibiotics we're going to use and how long we're going to use them for like we are playing darts because I don't know about you but my accuracy is not very good and so if it's just random what you're picking you're likely to either run into treatment failures or you may be going overboard such that you are causing potential resistance or side effects for the patient you're not doing them any benefits okay so why is this a concern well because we start to see the emergence of more and more resistant bacteria that don't really respond to what traditionally works well so for example you start to have let's say staff orius well back in the day there wasn't methylin resistant storus but it started to develop and become more common in response to people treating staffor infections have MRSA so a drug we'll talk about later that is used to treat MRSA infections called vomisin well guess what then you start to see venamy resistant staff oras at VSA that you see there or venamy resistant in acacus and so things will start to develop infection resistance I should say over time another group especially G negatives gam negatives are really nasty because basically what they'll do is they'll share these little plasmas of DNA with one another they'll be like hey I got a hot tip for how to fight this this carbapenam and make a little plasma and just send it off to another bacteria all of a sudden they get that new code basically unlocks and then says okay now I'm resistant too and so you can see they'll start to develop enzymes like exended Spectrum betalactamases they'll start to have carbapenemases these are all enzymes that they can now produce that basically destroy some of our drugs that have um you know and I always talk about antibiotics in terms of like Weaponry um so some antibiotics is like a f water and some antibiotics are like a nuclear bomb again which Armament you pick which antibiotic you pick is going to be dictated based off the severity of infection the type of infection and so in these cases here you have these bacteria that are producing enzy s they're basically destroying your best weapons and so once you get resistant to these there may not be a lot of other steps to take there may not be a lot of other Alternatives and again if you're thinking about it from a drug company perspective would it make more sense to make a brand new medication for diabetes you could also sell for weight loss you can Market to millions of people or would you rather make a new antibiotic that maybe only several thousand people a year are going to use well well monetarily speaking it makes more sense to go make the diabetes Med right and so because of that you'll see that there is are very few new antibiotics coming out from year to year thus making it difficult to outpace the resistance that we see so how do we prevent that well it's through very judicious use of our antibiotics following guidelines following your cultures not treating for too long not double covering all these other things that we can do as practitioners to make sure we're making the most out of the drugs that we have because again in the future we may not have a lot of Alternatives so we don't follow guidelines we we don't deescalate or streamline therapy when we should meaning going from a uh more broadspectrum antibiotic down to something a little more simple when you we have cultures that show that we could do that um you're treating for infections more than you need to so your prolonged period of treatment um and then even consider things like you know how long is a patient on the ventilator if they're IND have the indot tral tube in place they're iated like I mentioned a big tube of plastic going down their lungs could be a great source for bacteria to get introduced into that area to have a noomi infection so let's get them off the vent as best we can because it helps to prevent those noomi infections here um prolong hospital stays I think the shorter time you can spend in a hospital the better because you're less likely to have medical errors happen you're less likely to have these secondary infections happen so get them out of the hospital is a great idea to do that and then um looking at prior antibiotic use it's another big one because if you're using antibiotics prophylactically or if we using too broad a spectrum of antibiotics using too big of a gun for what we really need it for then that can end up leading to again overuse of these broads Spectrum antibiotics and then U leading to resistance issues right anyway so again why do we see so much resistance um a lot of it is not necessary from just human use some of this is through the use of antibiotics for animals for livestock pigs and chickens and cow and things like that so again it's not just our problems as medical practitioners but we do see as they get exposed to more antibiotics they're producing more multi-drug resistant microbes andless then pass them on to us and so again that's another consideration you'd be thinking about and there are lots of ways that these anti bacteria become resistant in some ways they modify the targets that the drugs are actually looking for so they may either change protein structure they may change the actual amino acid sequence um some cases they may have more e-lux pumps or they can actually shuttle drug out of the bacteria they may do things like you know remove channels that prevents the antibiotic from getting in either way however they're doing it is not so important to consider but point being is it through these methods they become resistant they make it more difficult to find a suitable drug to actually treat those infections especially considering some of the collateral damage that can happen from using some of these more broad spectrum antibiotics here so what can we do well usually most organizations will have what they call an antimicrobial stewardship program what does that mean well basically they try to be good stewards of the ant antimicrobials that we have and use them as wisely as possible and so this can include things like changing your formulary or restricting your formulary this could include things like following treatment guidelines you may have cases where you are cycling out certain antibiotics to where you can say okay for this couple year period we're GNA use this one and then we'll cycle it out to use a different one to kind of relieve some of that pressure to cause resistance to occur um we may do things like put restrictions on what you can order so for example if you're working down in the ER and you say hey I want to use this antibiotic that's like super great and treats everything I want to use it for this patient here you might get a call from the pharmacist being like actually about that yeah did you get infectious disease to uh sign off on that and you're like excuse me you're questioning what I ordered I'm the PA here I do what I want in some cases we got to tell you uh actually no you got call infectious disease and have one of them sign off and so we might actually put restriction on that so that way you're not just using things willy-nilly you have to make sure that someone else who is an expert in the area can sign off on it be like yep that makes sense your case is good let's go ahead and let's approve it otherwise you don't get no drug so again these are all tactics we do to try to manage and try to curb resistance as best we can okay so enough about that let's get into the actual antibiotics themselves and some of the principles we're going to consider when we are choosing an antibiotic so first of which is spectrum of activity that's kind of what we've been talking about so far so does the antibiotic that I'm choosing have activity against the bacteria that I think is most likely present within this patient so if I think someone's cominging in with an atypical pneumonia meaning caused by chlamidia or Legionella or micoplasma if I'm assuming that does the drug that I choose actually have coverage against that particular bug or set of bugs that's the first step because if it doesn't then pick a different drug altogether from there you then consider the kinetics of the drug itself so we think about things like the absorption does it even get absorb to the system can it only be given IV can it be given po those are considerations does it distribute and actually get to the body compartment we want it to you'll find for things like menitis that certain antibiotics can cross the blood brain barrier just fine and they have an easy time getting there to treat the infection some other drugs though are way too big and they almost can never get across so if the drug doesn't even get to the side of infection it can't do its job so it's no good you also need consider the elimination because we don't want these drugs to stick around for forever and you'll actually find that some of these antibiotics especially some of the common ones have a low therapeutic index meaning that even at you know slightly higher than normal dosages you could if insensitive enough patients run into problems where you have things like renal dysfunction hepatic dysfunction have hearing damage damage for example so lots of stuff can happen and so because of that we want to make sure that we consider the kinetics for our patients and again these things can change from day to day especially in really critically sick patients here from there we want to consider the pharmacodynamics for these antibiotics here so some terms we're going to use and we'll talk about here in just a moment are going to be whether the drug is bacterio cidal versus bacteriostatic and we'll talk about the difference between time dependent killing and the concentration dependent killing so I'm going to talk about those in a moment here but the next thing here I want to mention are the toxicities and again it's nice that a lot of antibiotics are pretty specific for treating the bacteria I mean they're try not to kill off our cells they want to kill bacterial cells not ours um however it does not mean that these are without toxicities and so as a result of that you're going to see that there can be GI issues show up there can be things like hematologic toxicities renal injury and so we need to be cognizant and be monitoring for these things some of which we know we're going to be more common than others but we need to be thinking about them more impatience about them be like hey if this happens then maybe you need to come back in and see me if this happens that's normal that's totally fine if this other thing happens go to the ER right away and so again by educating talking about these things patient can be well aware of what's happening to them that just isn't you know further development in their illness it's actually related to the drugs we're using to treat them so bacteria Cal versus bacteria static generally speaking does the back antibiotic kill the cell outright or does it just inhibit it enough such that it's not going to be actively replicating and remember when we treating an infection it's not just antibiotic that's doing its job but it's also the patient's immune system that is helping us along so in some cases by putting a bacteriostatic antibiotic on board that could be inhibiting the bacteria from growing just enough to allow your white blood cells to come in and then finish off the job so bacterio cdal kills the cells outright this will include drugs like things like your penicillin seos sporin and we'll talk about why that is specifically when we get into the mechanism of action kind of make some sense as like to see oh yeah this makes sense that it kills the cell out out right versus other drugs are going to be that bacterio static it's not to say that bacteriostatic drugs are worse than bacterio cdal they all have their places but it's just different in terms of how they're going to be affecting the cell and so things like your tetracyclin things like your macrolite antibiotics have fall into this bacterio static category another consideration to you always want to think about I mentioned how your own immune system is working in conjunction with the drugs is what the patient's immune system isn't all that are doing all that well so what if you have an immunal compromised individual is their immune system even up to the task to be able to help the antibiotics out and so are situations where if I have someone who has a really poor immune system system let's say for example they're on chemotherapy and their nutrifil count is like two or if they have really uncontrolled hiv/ AIDS and their CD4 counts like undetectable there those are instances in which we may prefer using something bacteria Cal because there we are assured that's going to be able to kill off that bacteria entirely as opposed to just inhibiting it so there are some considerations there but generally know the difference between when I say something is bacterio cdal versus St be able to describe the difference between those two okay and then we get into whether a drug is considered to be concentration dependent or a Time dependent killer what does that mean so basically what this means is I'll show you some pictures here in a second is that for concentration dependent Killers antibiotics the higher the drug concentration is the greater The Killing we're going to see and even if levels for that antibiotic drop very low we still have bacteria dying off because of something called the post antibiotic effect or PA AE so even if you couldn't detect the drug level there's still enough residual effect around such that bacteria still dying off even before the next dose you give you I'll show you a picture of what that looks like in a second here time dependent killers are only going to be able to kill the bacteria while the drug concentration is sufficiently high to prevent this bacteria from getting back online starting to reproduce on go mitosis all that stuff so there's a term here we're going to use this called the minimum inhibitory concentration mic that is basically the lowest level of a drug that will be able to achieve its intended effect to either inhibit or kill the bacterial cell outright so for a Time depend a killer we need to stay above the mic for as long as we can ideally 100% of the time because there's no postantibiotic effect meaning once the drug level drops below the mic bacteria is going to start to replicate again and so because of that time dependent killers are frequently either given more frequently so they'll have a smaller interval meaning maybe I'm giving something every 6 hours every eight hours whereas with the concentration pend just using something that's going to be every 24 hours right so that can sometimes factor into the actual frequency of dosing as well if you go back to our kinetics lecture we talked about the differences between something you give a big dose one time a day versus a smaller dose three times a day you get differences in those Peaks and troughs and for a concentration b a killer one time a day is great because I get a high peak that's what I'm looking for time dependent Killers though you have to give more frequently in order to get those higher troughs to keep it above the mic to be able to continue to kill those bacteria off so what does this kind of look like well if I was was to compare the drug concentration of Time Versus uh concentration on the y- axis here um you'd be able to see that for a Time dependent killer if you notice here so let's say the mic is say three if you get down below this concentration you notice the bacteria starts to grow again starts to become more cloudy because there's more cells present there so I want to keep for a Time depend a killer I want to keep it above this M for as long as possible the term will sometimes used to describe that called the Au or the area under the curve either way what it just means is once we drop down below this mic bacteria going to start to grow again so we want to keep it for a Time dependent killer as much time above the mic as possible which you can see here so for example there's a group of antibiotics we're call the betal lactams they need as much time above the mic as possible on the flip side though if I'm looking at a concentration depending killer and so the example here would be our aminoglycosides they want to get as high of a concentration as possible and even if we dip down below the mic that's okay because it's a concentration b a killer it has post antibiotic effect meaning if the level drops down too low you're still going to get that nice effect from the drug bacteria is not going to grow and then you hit the patient with the next dose 24 hours later maybe okay so another the difference between time versus concentration minut killer and be able to describe that and so here the general category of antibiotics again I'm not going to go into as much depth as I might if I was doing this in farm one this is just the introdu ction get your feet wet just to get you exposed to it so that way you can be like oh yeah I think I remember what are you talking about a cell wall inhibitor and the penicillin is one of those and again we'll give you kind of the general rundown here refer back to that so how we're going to be breaking up the categories of antibiotics is largely going to be based off of their mechanism of action okay so first of which are going to be what we call cell wall Inhibitors this is a big group and includes one category called the betal lacum antibiotics and I'll describe what a betal laim is here in just a second it also includes your penicillin your sephos sporin balacas Inhibitors we talk about all these and then also includes a drug called venamy Venom a little different than the betal lacum we'll talk about the differences in just a bit these are all your cell wall Inhibitors okay then you get into your protein synthesis Inhibitors and we'll talk about how those work but basically these are going to be affecting the ability for cells to produce new proteins and if you can't produce new proteins you're not really going to have a very functioning cell so again I'll go into more depth on the mechanism just a bit here but this includes big categories like youro glycosides tetracyclin macrolides clinty for example here and then we're going to see there's things we can use that inhibit the sort of nucleic acid function or the synthesis of nucleotides and things that get Incorporated to DNA and RNA similarly here if you don't have good functioning DNA if you can't produce new copies of DNA you can't undergo mitosis so it's another way we can arrest cell growth and cell proliferation by disrupting this process here so in FL quinolone metronidazol will fit into that category as well okay so as I mentioned we're going to see that the betal lactams include things like your penicillins again I'm giving you some representative examples I'm going to go into more details on these here in just a little bit um things like your sephos sporn if you ever heard of like klex or seaner where these fit in here along with your betal laimas Inhibitors um so for example if I'm putting a combination of amoxicillin plus clavulan this is considered to be a beta lactase inhibitor I'll talk about what what that does and why it's important here in a bit and then we'll get into vomisin which is kind of like your gold standard for treatment of Mera and a lot of different skin soft tissue infections joint infections things like that we'll get into as well um within the category of betal lactams we're going to see here you'll have Penicillin classes so again this is like umbrellas within umbrellas within the penicillin we have what we call the natural penicillin this is not spelled incorrect correctly natural penicillins you'll have the anti-sta laal penicillins then we get into our extended Spectrum penicillins anti demonal penicillins and then we'll talk about the combination of penicilin plus the betal Lacamas inhibitor I'm going to go over all these in more detail in a second just TR to give you the overview so you kind of see the umbrella type of structure we're dealing with um similar to this we're going to see the sporns monobactams and carbon penams the things that tie all these together all the different classes here together are the fact they all contain the beta lactam ring what is that it is this fourpoint structure here this is the business end of these antibiotics this is what actually interacts with the bacterial cell wall to cause disruption to cause cell death is this Square core here all of these contain the beta lactam ring what's different though is all the stuff to the side all these other side chains here are what's going to be different and that's what's going to dictate its difference in antimicrobial coverage to where something like a natural penicillin pretty wimpy but then by changing the structure in the side groups you get up into your carop penum which are basically like nuclear weapons essentially they nuke almost everything and so there's a very fine sort of progression here from the very natural penicillin which is the first antibiotic we ever had all the way up into like our carbon penins we'll talk about more detail um within the natural penicillin this is where you get into things like penicillin V or penicillin G this is just a straight up penicillin like the straight one we got from the mold way back in the day this is the very first one we had here but from there they started to develop them for other uses so for example um they talk about ones that are going to be anti- staffo penicillin so these are ones going to be useful for treating things like mssa or methylin sensitive staff oras and so this will include things like dxic silin nyin and an oxicell you then get into some of our extended Spectrum penicillins these are also known as the amino penicillins amiop penicilin so this is like your moxacin ampicillin if you work in Pediatrics you're going to get very familiar with moxacin you're using it all the time these in other places as well but definitely impedes for sure and then we get into our anti pseudomonal so these are interesting because um pomonis in particular is a very nasty gram negative bacteria that um can become very resistant to to a lot of antibiotic classes here and so we had to develop penicillin that are very specifically useful against that pseudomona so if I assume my patient has a nosocomial pneumonia coming from a nursing home I might have reason to believe they have a pomonal infection I may need to bring out these really broad spectrum antibiotics like pyin or ticker aylin so those are kind of like your heavy duty killers there and then in some case we'll actually pair the penicillin plus something called a beta lactam inhibitor so one reason that these uh penicillins become or the bacteria become resistant to them is because some of them start to produce an enzyme called Beta lactamase And so what does that do well betal lactamase basically Cleaves this ring here if you could break up this betal laam ring antibiotics not going to do anything anymore so instead if we can give you a beta lactamase inhibitor to keep that enzyme busy it allows your penicillin to do its work even more effectively so for example if you ever heard of augmentin is a combination of oxicell plus clavulanic acid those two together increases the spectrum of activity for Amoxicillin such that is able to kill more bacteria and a more wide variety of bacteria than amoxicillin by itself similarly you see the combination of ampicillin Plus sbam soam in this case here is the betal Lacamas inhibitor or piperin taso backdam one known as zosin this is really this is like they call it gorilla cylin sometimes because it's such a big player it kills so many different bacterial strains uh but also it's prone to overuse and prone to resistance as a result of that so this is one of the examples of a drug where we might actually require infectious disease approval before you actually get access to it potentially then uh we'll get into our seis sporns another very common class antibiotics are going to run into these actually get broken up into generation so the first generation with the first ones to come out here this includes very common ones like ANF or seolin some people say seasin let's say seolin if you work in surgery you're going to see that all the time because that is used for surgical sight infection prophylaxis so whenever you're going to slice into a patient there's a potential despite how much of antiseptic use you have and good sterile technique there's always a chance a bacteria could get in there and cause a surgical sight infection and does Insurance want to pay you for that to treat that heck no they don't so infection control is really really important and one thing we do before you go to surgery within an hour so we're going to give you a dose of ANF and that prevents you hopefully from getting a surgical sight infection so think some of these are IV some are po so some of these are going to be able to see out in the you know General use by outpatient use and some of these are going to seem more relegated to like in hospital use depending on which ones which we'll get into more details later on um you have a second generation here an example would be sephir oxine then we get into our third gen sephos sporns these are um even more broadspectrum than the first and second uh a good Workhorse antibiotic is rosin SE triaxone that's when you're see used all the time it's given as an IV or an IM injection um really good coverage treats a lot of different types of infections and it's really easy to dose people like it because it's so simple to use you just say one gramar R and q24 IV boom done you don't have to worry about kidney function you don't have to worry about other drugs are on it's just easy lot people like it but again overuse can lead to resistance and then we finally get into our fourth gen uh seis borns here there actually a fifth gen which I'll talk about a little bit later on um it's a fourth gen would include drugs like sapine this is very similar to that drug piperacillin I mentioned before in the penicillin as it is a very broad spectrum drug treats Pamona so again gets used for a lot of those nosocomial type of infections um then you get into the monobactam class there's one drug here it's called asram and then carbapenams again are another class of really broadspectrum antibiotics these are like you know something like aipim or pipper cylin is not able to treat that pseudomonal infection car caroms are the even bigger guns we bring out so always consider carpet penum like you know the nuclear bomb of penell essentially or betal lactams I should say U so things like meenum mum get used here so how these are going to work all of those classes I just mentioned are working through the betalactam ring and basically what they're doing is inhibiting cell wall synthesis so there is a protein called The penicilin Binding protein I'll give you one guess as to where we came up with that name at but basically the binding protein is responsible for producing the kind of interlocking layers of the bacterial cell wall and so if you disrupt that protein from doing its job you are not going to have a very structurally sound cell wall and in fact it will start to break up and it will start to open up and so just like punching a hole through a wall stuff can start to leak out I guess any walls where you can punch in stuff imagine punched a big you know water balloon stuff's going start pourn out and basically that kills the cell because you can't really survive you have a big giant holes gaping holes in you all your stuff's leaking out so in that way betal Latium antibiotics are bacterial cyal because by open up those big holes all the stuff lices out of the cell is dead it's cooked done so betal laams are all bacterio cyal in the way that they work there so as you can see here there's interfering with the bacterial cell while synthesis because they bind to this peny binding protein it's not just the penicillins that bind to this penic Bing protein it's all the betacam Rings all the betal latim classes we just saw there carbapenam sephos sporin monobactam they all do the same thing here so their mechanism is all the same so if I asked you on a test question I said what's the mechanism of action for betal lactam antibiotics you'd say disruption of the cell wall I could go even further then I could say well what's the mechanism of action for rosan T aone okay then you got to figure okay what kind of drug is Seth Triax okay remember oh yeah it's a it starts with SE so it must be seos sporin sephos sporin are betalactam antibiotics oh yeah betalactam they interfere with the peny mining protein they disrupt the cell wall so by going through that kind of hierarchical system you don't need to know the mechanism of action for every single drug you can simply know what's the mechanism for that group of drugs and knowing that se sexin Falls in that group is easier to remember than having to memorize each individual drug separately so when you try to organize these out try to do it by grouping them into greater classifications so if I can put okay betal laum is one big umbrella you say Okay within that umbrella I got my penicillins I got my seil sporns my mams and then Under the Umbrella of sephos sporns you say okay my first second third fourth generation under penicillin I got my anti stacle my anti sudal mop penicillin so try to group them together in such a way such it makes it easier to kind of go through that high hierarchy as opposed to memorizing each drug as an individual entity grouping will be really important to help you kind of put everything together when we get into it as I mentioned resistance is a big problem and so a lot of bacteria started to get kind of wise to the actions of the betal lactum drugs and decided to make betalactamase so that one would basically cleave the betalactam ring right there basically make it ineffective so if I cleave that ring the drug can't bind to those peny binding proteins anymore it's not going to do its thing other ways that they have um develop resistance can include things that decrease permeability so if the antibiotic can't really penetrate through enough of the outer cell membrane it may not be as effective or the bacteria may have evolved to have modified peny binding proteins where it has less affinity for the betal lactans itself so these are just ways resistance can develop and may require us to go from one set of drugs over to another is because of this resistance patterns will emerge so going into a little more detail on these we can see that if we start out the very Basics we go straight with Penicillin penicillin as we can see here um has pretty narrow spectrum of coverage here but it still has good coverage against several things that you're going to run into somewhat commonly so for example um we still have pretty good coverage against like syphilis so we've been treating syphilis for hundreds of years um and so penicillin still has good activity against it and so in some cases resistance really is never a problem other cases it is and and so for syphilis you still get a Shad of pen ayin and you're good to go um you also see it potentially being used for some things like you aerious species things like that um like I said remember these are bacterio Cal however this applies to all the betal laams they are time dependent Killers so if you were to compare dosing strategies between something like penicillin versus say aor quinolone you'll see that the penicillin has to be given more frequently could be every 8 hours could be every six in some cases there are certain types of infections say for example someone has a uh say an infected case of endocarditis their valve gets infected in some case we use penicillin itself and we'll do that as a continuous infusion so we'll be giving the same dose every 24 hours over that whole 24-hour period because that ensures as much time above the M as possible just to illustrate that it's a Time dependent kill that applies to all of the betal lacum antibiotics here um using or going up from your basic penicillin to things like a moxacin for example and ampy fits in Category 2 again same mechanism side effects are going to be very similar just the spectrum of coverage is what's changing here really so they's still time dependent Killers there're still bacteria Cal so as long as you know that all the carb or I'm sorry all the betalactams have the same mechanism they're all bacteria ital and they're all time dependent Killers you now know every drug within that class fits the same bill there so look for the similarities between the drugs to more effectively categorize them and then you can start to spot the differences little unique sort of idiosyncrasies that will delate one drug from another like maybe a very particular side effect that it causes or a very particular allergy you got to watch out for whatever the case may be so Moxy gets used a lot um typically has a little bit better coverage against a lot of things like respiratory infections and bugs are likely to there so sometimes we use this either for treatment of those conditions we may use this in some cases like prophylaxis if you have like really high-risk patients maybe like poor immune systems or if you're trying to prevent something like a bacterial endocarditis um so a lot of different uses for these generally speaking your penicillins things to worry about rash rash is somewhat common but again nothing lifethreatening generally speaking in some cases though patients are having a true hypers sensitivity reaction which can include axis and so this is one of the problems you're run into because and this is kind of a soap box I'll get on for a second here um whenever you say oh patient has a penicillin allergy anytime you hear an allergy the next question should be what was the reaction because if they say diarrhea that's not a true allergy that is a side effect of the drug and it makes sense because as you give the antibiotic it's going to disrupt your gut Flora it's going to cause diarrhea that's just natural it happens saying you have a allergy to penicillin and you say oh I had Anis I almost got intubated got the epinephrine all n yards that's a true hypers sensitivity so you want to be cautious when trying to evaluate these things because um some cases you could be kind of in the gray area where they're like I got a little bit of a rash when I got a peny so I just told them I'm allergic okay so do you want to rechallenge that or not is the question and so depending on what the patient tells you what their history is you may may not be may or may not be is likely to want to rechallenge that because again no one as a healthcare provider wants to cause anlis in your patient we don't want to cause the patient to have a bad outcome and so providers are to some degree warranted are are a bit hesitant to push the envelope for a lot of those things so just something to consider um other problem too is that when you say penicillin they may not actually have been penicillin it could have been another agent um but generally speaking if someone has an allergy to penicillin or anything within the penicilin group the whole group's cut out at that point so if this say yeah I had a had a true anif flacc reaction to Amoxicillin you basically cannot use any other penicillin in that group and that's a problem because now that cuts off a whole bunch of really good drugs to ever be using that patient in some cases there may not be a lot of good Alternatives so it's really important to first of all identify did they truly have an an allergic reaction and if so then okay document that but if not um then consider okay well is this person a good candid to go and try this again to see are they going to have a bad reaction here and so there are some cases where I've had conversations with providers in the ER and you know they may have had kind of a a very edge case it seemed very remote chance that the patient was going to have a true reaction if they were use this antibiotic and I said okay well you know the chances are very low but you know let's just do a test dose in the ER because if they're going to have a bad reaction you'd rather be in the ER than anywhere else and if they don't have a reaction they can take the drug and tolerate it maybe they're good to go maybe we can take off that allergy off their profile entirely and so we've done that in several cases and it usually turns out just fine again there's always off chance that they may have a true hypers sensitivity but it's fairly rare for the most part okay so getting into seos sporns same mechanism as penicilin nothing different here um they're still affected by the same types of resistance mechanisms again the really big thing that changes here are going to be what these side chains look like so they had this kind of ring structure here and these different side chains they'll delineate which seos sporns you have but the same core here the same betacam ring is still present so that makes resistance issues um mechanism of action all that's going to be identical between the groups there still bacteria Cal still con concentration I'm sorry time dependent Killers I should say because again you want to keep above the mic for as long as possible and so what's neat about the seil sporns is that as you go up in generation you'll see the spectrum of activity start to change a little bit to where you have pretty good Grand positive coverage early on on then as you go up in generation starts to kind of dip down and then around fourth gen starts to go back up a little bit but if you notice the G negative coverage meaning the variety of gram negative bacteria that it treats is going to be on a steady uptick all the way throughout to the point where um you know maybe you're only getting like very kind of Basic G negative stuff with the first gen like maybe a little eoli here and there maybe a little bit of clella but then as you start to work up to the generations you get to a point where like oh now we can actually treat like pseudomonas like there big scary bacteria potentially big scary gra negative bugs um nothing we've seen so far though is good against Mera and so when I talk about big scary bugs the two big ones I always allude to most often are pomonis and Mera and so so far we've seen a couple of drugs that can treat pseudomonal infections like I mentioned uh sephine which is a fortune sephos sporin uh mentioned piperacillin Tas aaam it's another good anti sudal penicillin um I haven't seen anything yet that treats Mera so when you hear Mera or ponus ear should prick up about that because those are big considerations if we need to cover for that or not so as I mentioned you're going to get the most grand positive coverage in the early Generations so things like seolin or um uh seilin fall in this category here and as you go up you're going to see better and better gr negative coverage so in particular like the third gen sephos sporns like seaner like seaone those are bread and butter type antibiotics if you're worried about most gram negatives you can get away with the third gen seis sporn and you're good to go um fourth gen is when we get into that pseudomonal activity so this is where you get the sapim here there's there's even a higher grade now things like SE terene um those have very specialty type of coverages and you'll tend to find that when you see new antibiotics come out we try to reserve them excuse me uh like they're fine china basically sorry for the burp um so we don't want to bring them out just for any old bacteria if I can get away with like the paper plates of like a penicillin or sexin I can use that for anybody coming up you know Bubba coming down from down the street coming up for for some barue he ain't getting to find China but if like your grandma's coming over and she's got that really judgy judgy sense you got to make sure everything's super clean in the house you want to bust out the Fine China for her so you got to make sure that we are very um selective about when you bust out these new antibiotics because they're nice and shiny and new when they first come out but overuse will end up causing more resistance you want to reserve those new ones for when you do have you know those resistant bacterial infections start to pop up because you may not have a lot of other options there so generally speaking at this point I don't know that I'm going to have any test question that will say hey specifically can you tell me between a first or second or third generation spilos borin we'll we'll drill down more detail on that I think in the fall but you should be able to recognize all these drugs as a sephos sporin and based off of knowing that it's a sephos sporin you should know what it mechanism is should know that they're bacteria Cal should know that they're time dependent Killers similar to all all the other beta laams so again start to try to group these in their categories together so you can start to say okay what are the commonalities amongst these different groups These are nice because this is just a very large umbrella of betal laum drugs we'll start to get into some other umbrellas here in just a bit but start with the grouping thing generally speaking so one thing that um some people still believe or still are taught are that if you have a hypers sensitivity to penicillin you cannot get any other beta drug because they're both betalactam so if I have a reaction to the to peny I should have a reaction to all the other ones right that's not true because it's not really the beta lactam ring is what people are having an anaphylactic reaction to it's all those side chains and so if the side chains look appreciably different to your immune system the body's not going to have a problem with that for the most part and so for a long time people thought well if you have a penicillin allergy you're probably going to have a reaction to sephos sporns too so we're just going to knock out both groups and so for a while like you said you had penicillin allergy you knocked out like seor and penicillin that makes up like I don't know 75% of all antibiotic usage it's just random guess but that's probably pretty close and so you run out of a lot of really good options or you at least cut yourself off from that well part of the problem was why that happened was because back in the day we used to require to grow the mold to produce the antibiotics and so you would have a lot of cross-contamination you have mold that mainly produce penicillin but they also made a little bit of sephos sporn in there too and vice versa so you'd have contaminations between the products there now all these are synthetically made there's no cross-contamination so they have actually found that if you have a true type one hypers sensitivity true antic reaction to penicillin the chances of you having a reaction to a sporn are extremely low some people approximately about 3% of seen some estimates to be less than 1% so this is the uh the situation I get into with providers where they're like well the patient said they had a penicilin allergy but it was when they were baby and they're not really sure what happened but it's in the record it's in the mar that says hey they have a they have an allergy and I get a flag when I put in for the sefalosporin I said well I said well listen the chance of hypers sensitivity are super super low let's just do a testos here in the ER and I showed them the data and some people still say no a lot of people newer providers will be minable to that give them a testos and guess what they do fine and that's really helpful because now once you have at least one documented good case where it did was not a problem then you can use that moving forward and so that's one of the first things I always look up whenever I have patients who have a documented penell sepor allergy I look to see what they've received before and if they've gotten like a million doses of seos sporns previously not had a problem well then there's no reason you can't keep doing it from now on because again you're going to get those warnings those flags in the system not all of them should be listened to they should be addressed but you don't necessar have to listen to everything they say you can say like well with context that's not really going to happen in this cave anyway other common side effects nause vom diarrhea that probably applies to every single drug we're going to talk about from here on out nause vom diarrhea so if I ask you which drug causes nause vom diarrhea it's all of them they all can cause it but again things like diarrhea are going be much more common with antibiotics just because they are disrupting the gut flora and so again that's very common side effect we can warn patients about that hey make sure getting good oral intake of fluids maybe some pedite you know especially having pretty severe vomiting or diarrhea but these are not anything really to be all that too concerned about all right I mentioned you can sometimes get into cases where you're mixing the betal laimas Inhibitors plus penell so for example amoxicilin plus clonic acid Augmentin another common antibiotic you're going to run to espcially ineds um the nice thing about this by including the ba lactamase inhibitor you start to increase anerobic coverage so this is really the first spot where we're starting to see Anor robes being covered here for things like if you had say uh cat bite or a human bite or you had something like you know diabetic foot infection there are cases here where there are more likely to be anerobic bacteria present so these provide good coverage against that also now we start to see some coverage for mssa so now we're start get a little bit of Staff orus coverage here too so in lots of different cases we're going to be using this again still bacterio Cal still tendent killer it's just that the betal Lacamas inhibitor makes the penicillin do that much better work just broadens out the spectrum of activity just works a little bit better all right so then switching gear now we're going from the betal lactams but we're still sticking with our cell wall active drugs here this is where we're get into one called venamy if you're not familiar with vamy super common in the hospital setting this is our go-to drug for treating MRSA so if you want to star that or underline what the case may be um this is your go-to drug if you suspect at all that your patient has MRSA infection skin soft tissue infection um coming from a nursing home with pneumonia anything like that you want to suspect MRSA could be present and again A lot of times when we're treating empirically for patients what we'll do is we'll start out with these bigger Spectrum guns start these bigger Spectrum antibiotics and then once we get culture sensitivities back we actually know what's present then we can start to scale things back down so it's not unreasonable someone could start on a vamy we get the results back that says oh actually it's not MRSA it's mssa so methon sensitive staff orus okay I don't need the vanum is anymore I can then scale down to something like thicy or one of those other type of anti-aoc penicillin that's perfectly fine it should be done a lot of people will get into and again you want to treat the facts not the feelings so to speak and you know don't mean that in the political standpoint what I mean is um is that uh often times providers will do things because it makes them feel safer and not necessarily be doing the best by the patient and so one of the problems you get run into when you get things like cultures back from culture and sensitivity is that you'll say Hey you know you start them on broads Spectrum covers are on vam and they're on you know um peppero backdam and it comes back and it's just mssa okay I don't need all those antibiotics for that I can simplify the regiments but the patient's been improving their white Count's coming down and their fever's coming down and you're like well if it's not broke why go trying to fix it so you may be hesitant to want to change up the regimen if the patient's improving because you're like well what if I change it and then they get worse right so even though the facts will tell you that no streamlining is good it helps to reduce side effects and reduce things like hospital stays and resistance issues and all those good things it's hard to fight that feeling of like well what if what if I'm the one person though where that's not the case and so sometimes that can be a difficult um conversation to have or can be difficult to break people of that habit but it should be done streamlining from empiric therapy super super important because you're not just thinking about your patient you're thinking about all the patients that may be treated in a line in perpetuity right so VY here still a cell wall disruptor but it does not work the same as the betal LA betal laum drugs here basically it binds to different proteins and the cell wall but still causes similar disruption of the cell wall it's still bacterial cidal it's still going to lice open that cell and kill it off directly note here it's still a Time dependent killer meaning it needs to be given more frequently in order to stay above the mic for as long as possible and so if you notice here if you look at this guy it's a big molecule it's huge and in fact if you were to take venamy and orally it doesn't get absorbed systemically it's just too big to get through we still to give it Orly we'll talk about why but basically if you see General indications here anytime you see imersa come up vamis is probably going to play a role here to some degree interestingly though we can also use oral venamy so po only is actually good for treating clustr defal infections so we know C diff is a consequence of disrupting the normal gut floor usually with antibiotics and then you get the secondary opportunistic in with C diff and if you are not familiar with C diff it's not fun really copious amounts of profuse watery diarrhea it stinks like you would not believe and if you ever smelled it you know it you ain't going to forget it so we know in some cases anytime you give antibiotics to a patient there are some risk for causing C diff infections some drugs are more likely than others and I'll talk about that but when this happens we can use oral venamy and is able to treat that infection and what's nice about that is it doesn't get absorbed systemically so I don't have to worry about systemic side effects just doesn't get absorbed it's going be eliminated through the feces along with all the Dead Sea diff uh other things you can use this for endocarditis osteomyelitis any of those like difficult to treat gr positive infections it's great for that and then some cases if patients did have a true penicillin allergy we can use this sometimes as surgical prophylaxis to prevent those infections from happening in the first place so the reason why vamin should be used with caution this is considered to be a narrow therapeutic index drug meaning that you need to be very cautious how you use it you also need to be very um Vigilant and follow drug levels to one make sure that your troughs are going to be high enough to treat the infection but not so much so high that the levels start to accumulate because then you can start to see organ toxicity so in particular if you have two high levels in the body you can start to see things like autotoxicity where the patient may actually have difficulty hearing or hearing loss that can happen and it's not just they are not hearing but it could be more so um like muffled hearing or just difficulty Hearing in general um let me know if the stream is still working here feel like something funky going on my preview anyway regardless um so the autotoxicity ear toxicity calls nephrotoxicity and this is the drug that is entirely renally eliminated so if you're kidneys are not functioning you're not getting rid of those drugs can cause even further nephrotoxicity which is no good um other things are unique to vamy itself is called this infusion uh vomisin flushing syndrome and so this is basically where if you were to give this drug and Infuse it too fast you actually get this kind of body-wide sort of rash that will pop up and what's interesting about that is it's completely related specifically to the infusion time so if you do it too quickly you're going to get the flushing syndrome how do we prevent it well you slow it down and so where whereas some antibiotics may be given say over 15 minutes 20 minutes 30 minutes this one has to be given over at least like 90 minutes if not like two hours so you got to really slow it down and the problem with that is is that people will see this reaction and they will assume that it's like an allergic reaction and it's really not you don't need to treat with EPI and EP steroids and stuff you just slow down the infusion and it'll go away it's all fine other than that can be a little rough on the veins so you can see some fitis the fevers and chills kind of go with that flushing syndrome too so so just slow down the infusion you should be good to go from that standpoint all right so then moving on from the um cell wall inhibitor Inhibitors I should say um we then get into our protein synthesis Inhibitors and so big groups out of this category include uan glycosides tetracyclin your macrolides which includes things like a zithro and Croy and then and clomin as well so the difficulty here is where you're going to start to get into naming problems so so for example penicillins are pretty easy to differentiate from sephos sporin because sephos sporin start with seph Penicillin and encin now you're going to be seeing different classes that are going to be ending in things like M so aiom is different than tobery they come from two different categories one's a macrolide one is an aminoglycoside and again spectrum of coverage can be very different toxicities can be different and so coming up with a different naming con vention may be useful for you so for example in the macroides there's three of them there's aiy clery and erris a ace so if you know Ace you know one of those are going to fall into the macro like category so some of these you have to come up with on your own some of which will have some ponics we can use but again keeping these straight when it's they have very similar names can be sometimes difficult or at least students will have a difficulty there so how these are working are these are working to basically inhibit the ribosome within the bacterial cell by inhibiting the ribosomes you prevent them from producing new proteins so you can't finish you know transcription and translation and so by not producing new proteins you can't really have a good functioning cell because a lot of the internal mechanics are going to start to fail and so that helps to prevent the cell from thriving and undergoing mitosis and allowing for things like your immune system to come in and start to take over and kill the cell off so um the difference is in why these drugs affect the bacterial cells and not our cells because our ribosomes are different so they have different subunits that'll be affecting so for example uh for bacterial cells you see like a 50s and a 30s well for mammals it's 60 and a 40 they're different enough to where the antibiotics have that selectivity to treat the bacterial cells but not us and that's good because that selectivity means you have better side effect profiles so I don't really care if you know the difference between a 30s and a 50s binder as long as you can Iden identify these as protein synthesis Inhibitors you're golden that's all we need for this point in time here so as I mention in terms of you know things like resistance patterns that will develop similar things we've seen before so things like you know the bacteria producing new elux pumps or the change of targets things like that but starting out I'm talk about the tetracyclin as a pretty broadspectrum um player here and again this is working to prevent the ribosomes from doing their job preventing translation from uh finishing so you can't produce these new proteins uh most of your protein synthesis Inhibitors are going to be bacterio static because again you're just stopping protein production you're not doing something like ripping a hole in the cell wall like you know venamy does so it doesn't kill the cell off directly and some of these are going to be a little bit more variable in terms of whether they're going to be time or concentration dependent Killers so again organizing those based off of that could be useful as well um tetracyclin are nice because they treat many different types of infections whether um could be skin and soft tissue infections you know upper respiratory tract lower respiratory tra a lot of different uses for these uh as well here um so tetracyclin are going to include a couple including things like doxycyclin you may also see um minocyclin you may see um tetracyclin itself is also considered a tetracyclin again it has to do with it just has a four ring structure to it basically um you can use for acne treatment you may see this being used for um certain types of animal born diseases if you have like lime disease or Rocky Mountain Spotted Fever these get used all the time for that as well U and then certain actually transmitted infections and if you have like more resistant infections these are good there too so just giving you some examples of different places you may see these antibiotic classes being used here notable side effects with the tetracyclin it loves to bind to calcium and iron and kons in general here so this is one where you actually have to advise the patient to make sure that when they are consuming their tetracyclines or most commonly that they separate them out from things like ant acid products dairy products multivitamins iron supplements because they will bind together and they won't get absorbed you're just going to lose the tetracyclin in the feces and so patients may be adherent in taking their drugs like they should but the infection is not clearing ask about how they're taking it or what they're taking it with and make sure it's just glass of water and that's pretty much it no calcium no iron keep it away from all those type of products there um similar you can find that tetracyclin like to bind to developing bone and teeth and so in some cases we may have limited use for these in things like pregnancy and in Pediatrics because if you have kind of continued use there's been cases where you can see either discoloration of the teeth or have kind like brown spots in teeth of children this is really if you're going to be using it for like more than a couple of weeks is where you see this problem it's not usually if it's just like seven days um but also in a developing fetus you could see depression of skeletal growth so there one case here if you have a pregnant patient with an infection you may want to go opt for something different another big thing you can see the tetracyclin is a lot of photosensitivity and so again being out in the sun I don't know if you know but it's uh Florida and it is super hot out there um photos sensitivity is a big thing so they're going to go outside make sure they have sun block make sure they're wearing big floppy hat sunglass whatever they need to do to keep the skin nice and covered to prevent them from having a lot of rash and and burning going on there next we get into the macrolides and clinty again these are still protein synthesis Inhibitors the mechanism is identical here um and you can see as well these are going to be time dependent Killers so they're still going to be requiring in some cases the halflife of the drug will out will see the halflife will make it such that you don't really need to dose it that frequently so for example a ziy it's one time daily because it's a decent enough long halflife that it still has enough staying powers to where you don't need to give it multiple times a day so it really just depends on the drug um that category here we're going to have things like aomy lomy iomy are going to fall into these categories here being the macroides and the clites is kind of separate I'll talk about how that gets used a little bit differently here and again you can see a little bit of the difference here so for example macroides tend to be bacterio static for the most part whereas clites and bacterio cyal some of that stuff is just kind of memorization kind of keep a list of which ones fall into which categories there so slight differences um and again different reasons why resistance may happen here things we've kind of talked about before either changing of the protein structure or you know elux pumps and things like that uh and again we are starting to see more and more resistance especially maides get way too over overused um and it's so easy for some to come in with a head cold and be like Oh Mr or Miss PA you got to give me something can I get a zpack because they heard zpacks before they know they work and really it's probably they have a viral illness and they would have gotten better in two days anyway but if someone comes in to see you if they take time out of their day to schedule an appointment and actually come see you and they're feeling miserable and you said yeah it's probably viral just drink some P like going home you'll be fine patients don't like that they want you to do something and so um there is pressure from patients to say well maybe just write me one just in case what if I don't get better after a couple days maybe just give me one just in case you know okay zpack use a directed done don't do that don't fall for that trap if you think it's V viral don't worry about the Google review they're going to write for you say one star didn't do anything waste of money you can rest assur that you did the right thing by that patient right anyway so a lot of resistance especially for things like strap num numo which caus a lot of these kind of upper respiratory tract type of infections here um again you can see some cross resistance in terms of res resist from one class to another so some cases you may have cases where AIS is resistant to the bug and then it also kind of cross confers resistance of things like clom that can happen occasionally um so in terms of coverage with the macrolides the nice thing about this is it treats a lot of the upper respiratory tract infections or bugs are likely to be present for respiratory tract infections in general so for example um they treat things like H influenza strap num numo things like that the other difference with these though is these actually start to provide atypical coverage the macro or the tetracyclin do as well these guys will do this frequently as well so um if you were to have someone with like Legionella or if you thought they had like micoplasma pneumonia these provide good coverage there so when you have patients with they call atypical pneumonias usually the macroides or the tetracyclin are the first things used there because they're going to be able to cover for those atypical pathogens whereas something like a penicillin or sepor just isn't going to get it so that's one of their unique sort of points here so if you ever have um like a pants question and it says oh someone was at a conference at a hotel and a bunch of people got pneumonia and then the AC unit was infected it's probably going to be Legionella actually if you look up the orig origination for Legionella got its name it was an American Legion convention where an AC unit got infected and started giving pneumonia to all these uh old Legionnaire people uh and so that's where the name comes from point being though if you ever see that in a vignette you'll know it's Legionella give them a macrolite or tetracycle and they're good to go um clintom is an interesting one so this one is really almost exclusively covers gr positives and it also covers Anor robes so um gr positives and then almost all Anor robes or majority of Anor robes so G positive and gram negative anes so this is good for treating things like Mera infections skin soft tissue stuff osteitis and because it covers Anor robes you want to be thinking about like where would you find Anor robic infections well it's going to be places where there's not a lot of oxygen well the GI tra can be one of those places because again it's a lot of methane and carbon dioxide and things like that they're being produced through digestion and so there's not a lot of air there some people I mean they'll pass gas but they're not passing oxygen right and so as a result of that you can see that um gri inter bacteria can be prevalent there and so in this case here clom be good to actually help cover that the other big place you're going to see clintom being used or a potential problem with clintom you're going to see though is that it is because it kind of wipes out the GI track uh gut Flora you're going to find that um clintom is is associated most commonly with causing SE diff infections so that's one of the big kind of players there almost any antibiotic can cause SE diff infection clinty is just very well known for doing that un fortunately so through these you get some GI distress and motility issues you see cramping and things like that um rarely you're going to see ototoxicity you'd have to be on really high doses for this to be a problem here but as I mentioned clintom is most common for causing SE diff infections and then they can go on to develop something called pseudomembranous colitis um which is kind of a complication of C if infection so um clamy think C diff not to treat it but actually causes it and then use something like oral venamy end up treating that c infection there uh then we get into things that affect either nucleic acid function or synthesis is where get into our Flor quinolones which include things like cypro and Leo not sure why this is uh indented as well that should be on the same level as the CYO um the metronidazol as well so are fragile here so in terms of Flor quinland they are broken up by generations to some degree so you're going to see things like cypro and oxin Moxy and lolicin so again the naming convention fairly easy there um troxin will be kind of a newest one out of the group here and so what they're going to do is inhibit an enzyme called uh DNA gyate and topas so basically whenever you need to have enzymes come along and read DNA for like transcription for example um you know DNA is normally stored in a super helical sort of structure so when you need to have an enzyme come along and read that like DNA polymerase for example um you have to unwind the DNA how does that happen well one of the ways is to the actions of these enzymes DNA gyat and topias what these will do is they will cause Snips in the DNA allow it to unwind and then we'll reattach the Snips back together okay so if you give a Flor quinolone for example this will actually come and inhibit these enzymes so what happens is you'll cause these Snips to happen in the DNA you unwind it but then it can't snip it back together and so by causing all these Little Snips to happen they can't revert back the DNA will start to undergo damage and eventually the cell is going to be like hey this DNA is is totally botched like we can't use this at all um let's just go let's just commit apotosis right cell suicide and so it'll start that process where it basically kill the cell off so in that way florquin are bacteriocidal also concentration dependent Killers it's usually ones you're going to be seeing given like every 24 hours for example because they have a nice prolonged sort of post antibi effect so these get um similar to the zpacks and the macroides these get way overused because yes are good for atypical infections they cover a lot of the um respiratory tract type of infections here um but lot a lot of resistance over time so we're trying to really curtail when we use these and be very restrictive in terms of how we use these um interestingly with UTI Moxy flis and cannot be used for that the question why is that well most of your Flor Quinones get eliminated through the kidneys so they have to go through the kidneys and Mak sense that they treat UTI because that's where the Drug's at that's where the infections at oxyx only gets metabolized in the liver so it does not get filtered through the kidneys unless it never reaches the site for infection C so it's good for like pneumonias but Moxy would not be very good for UTI and unless you have you know document history of resistance these are way overkill for UTI anyway so if someone has you know frequent U or history of resistant bugs yeah these may be necessary but for most cases not not really all that needed um so again some of these will cover pseudomonas as well like Levaquin for example is a good one for providing pseudomonal coverage but some of that will differ depending on Resistance traits and and things like that so Flor quinon so similar to your tetracyclin these also will combine with cat so you want to keep these if you're taking orally separated from Iron ant acids multivitamins calcium all that stuff separated out don't uh you know have a cheese stick and then your florquin loans cuz some that's going to bind together and doesn't get absorbed um similar you can see photos sensitivity here so again keep your sun exposed areas covered up as best you can um and then interesting you see a couple other unique side effects with the floor quinon um one of which can be QT prolongation so if you don't recall the QT interval is the time it takes for the ventricles to depolarize and then repolarize okay and so if you prolong that by blocking things like potassium channels in the heart you can actually increase your risk for undergoing a particular type of ventricular rhythmia called torsa dupa or twisting of the points it's a French term um most people just call it torsades and so once you go into that it's a very particular arhythmia it's called twisting of the points um you'll kind of see this kind of flipping of the the wavelength of the way the heart's going on the EKG it's not good not compatible for life and so whenever you see QT prolongation you want to keep that in mind because as you start to add multiple medications together that canol on the QT your chances for going into one of these cases of torsades is going to go up and so if you think about a normal QTC interval being like say 440 milliseconds or so is a little bit long longer for women um you will start to get up into like the 500s the 600s milliseconds and at that point chances are that patient could then go into torsades and so I have to worry about this from like a talk standpoint because I could have patients overdose on these medications that can prolong QT where they're taking like Mega does um but you can run into this as well if they happen to have a patient who's uh has a history of aib and they happen to be on a medication an anti- rmic that prolongs QT and then you put them on one of these as well that could be just enough to tip them over the edge so for some of those at risk patients you may want to consider getting EKG beforehand so Flor Quin could be one of those examples there another unique side effect to the floor quinolones are going to be this issue of tendonitis and some risk for tendon rupture in particular the Achilles tendon in the back of the heel um not sure why this happens necessarily but is known to be associated with the Flor quinine so in particular more likely in children so if they're less than 18 usually we'll try to hold off on using Flor quinon or if we need to we'll say make sure if you have any joint pain heel pain anything like that tell us right away because it could be indicative of something more serious going on could be indicative of hey maybe need to stop the drug going to something else there and like I said resistance is a huge problem all right um how these are working as I mention or metronidazol next one here is working by actually binding to proteins and DNA basically a disrupting uh things like nucleic acid synthesis here um interestingly flagel also has some antizol antiparasitic activity as well so you can see it's sometimes use for those infections uh additionally there um still bacterial cyal it's another concentration bendic killer so you can give you know one big dose a day and that's usually good for for most patients there so with flagel this one's unique in that it's almost exclusively Anor robes and then also you'll get into parasitic infections like I mentioned last slide so if I had something like um this could treat CDE for example so i' use like Po metrol most commonly there if I had intraabdominal infections flal might be a component of the drugs you're going to use there and also for certain actually transmitted infections uh tricomoniasis for example would be treated with flagel the unique side effects with this one is the dul frame reaction so this is a medication you may see instructions say do not drink alcohol with this particular drug and the reason is because you can develop a dulam reaction what does that look like well it's not fun patients who consume ethanol while on this medication here will start to develop this kind of flushing reaction they're going to appear very red they're going to feel very hot they might be sweating they may get very nauseous and vomit it's very uncomfortable the reason why that is is because ethanol as to me metabolized through a couple of different enzymes one of which is called alcohol dehydrogenase which produces a product called acid alahh and then acid alide gets broken down by acid alide dehydrogenase the issue though if you have flagel on board though is that that second step that acid alide dehydrogenase gets blocked it gets inhibited so that means you get a buildup of this acid alahh and that's what caused all these nasty flushing reactions you can see a similar reaction in certain patients of Asian descent who happen to have a deficiency of acid alide dehydrogenase and so they're going to be more prone to having these kind of flushing like reactions it's the same mechanism it's just a matter of when the drugs inhibiting the enzyme and his individuals just could be lacking the enzyme so like my medical attending when I was in Fellowship his name was Dr kunisaki and he was a Japanese defense a descent um he would not touch alcohol with I mean he wouldn't be in the same room with the stuff practically because he just knows how sick and how you know R he's going to get when if he even smells it practically so educate patients hey don't mix these together uh actually a phist friend who his wife was a pharmacist as well they went out to eat at the Olive Garden one thing you'll see metronid being used for topically is for rosacea and so she' been using this topically uh went out to Olive Garden of course what do you get you get the endless salad and and bread sticks right but you also get a nice glass of Veno to go with it and so she wasn't even thinking topical flagel could cause any issue you drink a glass of wine all of a sudden her face gets beat red she's sweating waiters are coming up going ma'am are you okay do we need to call 911 for you look like you're having a heart attack she's like no it's a drug interaction she super mad at herself even though it's honest honest mistake so even farmacist can make mistakes like this but educate patients hey do not drink alcohol with this one while you're being treated for your infection there so anyway um other General adverse effects we talked about GI disturbances super common usually not anything to be worried about unless they get to that CI looking type of diarrhea very profuse watery foul smelling diarrhea that could be a concern there may need additional therapy um you know issues with secondary things like vaginal or yeast infections could occur here because again by putting suppression on normal bacterial Flora that can cause things like candidal species of fungus to start to grow so sometimes you see secondary infections as a result of this just depends on the patient if they're IM to compromise or not um other than that those are kind of the big things to really worry about in terms of General adverse effects from the antibiotics so again this is not everything this is just the general sort of overview of antibiotics a general introduction to get you ready to hit the ground running we talk about these uh in context of like things like otitis Medias and ENT stuff we talk about Dermatology stuff we talking about um urinary tract infections you know all have the context for okay how these antibiot are being used here so anyway so it does it for the last section here for the exam for the course what questions can I answer for you at this time assuming that YouTube's not lying to me there's still people watching uh the next question will be 30 questions I guess it is I'm not really sure I only have like one test for this class for my Orlando peeps but um um the trend is is 10 questions per section so um I would need to double check that but I'm going to say yes presumptively I need to look at the test and review it but um change that would be 30 questions so again broad Strokes kind of stuff here am I going to grill down or drill down and get super nitty nitty-gritty on selecting between a second and a third generation seis born probably not what I'm probably going to be more likely to look at would be things like hey can you pick out which category this drug fits in into so if I give you lexin can you say oh yeah that's a fluoroquinolone or if I ask you what is the mechanism of action of lolicin you should be able to say okay lolicin floxin flu quinolone okay I know the FL quinone how do those work oh yeah they work by inhibiting DNA gyas and Topo Ras all right be able to do that also things like unique side effects so for example we only talked about one set of drugs that really prolong the QT interval that's really unique you should probably know that or tendon issues or um causes that disol frame reaction those are kind of easy things I can pick on that are unique to those drugs that you should be able to then identify oh yeah it goes with this particular drug you know clintom most likely cause C diff that's a good one um things like that so what other questions can I answer for you at this time sorry if the video is any bad at all I'm going to go a just upload this recording as well and just presume I need to go I don't know what I need to do it's weird first time two times this has been happening but nothing on the sticky board more people have not had questions about the antibiotics but maybe you're just like information overloaded and probably like falling asleep on your keyboard maybe you could say but I just talked with uh Dr mckennis and I believe I'll be coming back for Farm one in the fall so as long as you guys don't complain too much and get me fired but say all beta lactams are all bacterio Cal and time dependent yeah so all beta lacam antibiotics every single one of them from your penicillins to your carbapenams and everything in between are both bacterio cdal because again what are they doing they're disrupting the cell wall they're opening up big holes in the cell so of course it's going to kill it off because everything leaks leaks out um they're all back to recital and they're all going to be time dependent so it means again they need to be above the mic for the majority of it dosing in order to keep that pressure on the bacteria to keep killing them off and so usually require more frequent dosing absolutely Kyle what other questions can I answer we need to specifically know the ribosomal suutes and their interactions um no I don't care if you know if it's a 50s or a 30s I would rather you know and identify each of those groups as being a bacterial synthesis inhibitor or protein synthesis inhibitor I should say so that's the granules I want to get from the mechanisms so if I said which one of the following would be considered a protein synthesis inhibitor I had penicillin lolicin metronidazol and aiy that's where you're going to go through each one of the okay which class that each one of these drugs fall into and then okay I know as a class this is what the mechanism is oh yeah well you know isi is the only one that was a protein synthesis inhibitor that's the answer right and you're still in the summer so we're still asking you know on the side of those kind of like level one level two type of questions um you know as we go forward and we get into you know once you get having your your uh medicine courses I we'll try to time it out to where the farm should be in sync with the medicine courses might be a little high little little behind a little ahead just depends on scheduling but the idea is is that when you talk about Derm stuff in CMS you're covering Derm stuff with Farm as well so those two overlap you can start to see um how they kind of gel together and order to kind of get more context so then when we go forward we'll be able to ask more uh clinical application type of questions to say hey a patient came in with this type of infection we think it's this bacteria which of these antibiotics do you want to use or this patient has this allergy which one should you use and you be like oh I can't use that one because this allergy is cross-sensitive with this particular thing so just something to consider there all right I don't see any other questions I think I'm going to go ahead and cut it here for today thanks again for joining me hopefully had a wonderful class session now we've gone through most of physio together and did uh then did arm together and haven't got any nasty emails yet so that's probably a good sign if I had to guess but um if anything comes up let me know otherwise have a great one and I will talk to you soon bye