Antimycobacterials | Anti-TB Drugs

what's up ninja nerds in this video today we're going to be talking about anti-mycobacterial drugs very cool one very short one nice right finally we can have a short video but when we talk about these particular drugs it's really important again to follow along with me grab the key grab the actual illustrations all the notes that we have at our website we have a link down in the description in the description box below go check that out so you guys can follow along with me i really think it'll aid in the learning process but when we talk about anti-microbacterial drugs there's a lot of different ones that we're going to talk about here but we should focus on how do they work what's their mechanism of action because if you're tested on that you should know what particular site and what kind of like function they interact or inhibit with and then after that we'll talk about what are they used for so we'll talk about obviously tb mac infections the super rare leprosy but if you get a question on the exam you'll know it and then we'll talk about the adverse effects that you got to watch out for all right so first thing when we talk about this actual mycobacterium you know in order for the actual mycobacterium to function it obviously needs to be able to replicate its dna and actually also transcribe its dna make particular proteins that allows for it to be able to control its structural and functional proteins we need that to occur we have particular drugs that can inhibit this cute little pink enzyme you know what this cute little pink enzyme is called this enzyme here is called rna polymerase and what rna polymerase does is it takes dna reads it and from reading it it makes a molecule called rna particularly this would be mrna now because it stimulates this particular step mrna then does what it actually interacts with ribosomes and those ribosomes will then synthesize particular types of proteins and these proteins can obviously be structural proteins they can be functional proteins but either way these bad boys are proteins and they're essential to the actual bacterial function well if i give this particular drug called rifamycins you know there's actually two particular ones that i want you to remember that treat microbacterial infections one is called rifampin this is going to be the very common very commonly utilized one and the other one is called rifabutin and rifabutin is actually an interesting one uh we utilize a little bit more commonly in mac infections particularly if someone is hiv positive rifampin caused a lot of interactions with the cyp450 system so rifabutin's a little bit more preferred but either way these drugs are going to inhibit the rna polymerase if you inhibit the rna polymerase can they take dna converted into mrna no so this type of reaction here will occur there's less mrna that's being formed that means that less proteins will be formed proteins are integral to the actual structure and function of mycobacterium you lose that you lose their ability to be able to survive they will then die so that's a really cool function of this particular drug now in the same way focusing at the nucleic acid level you know nucleic acids are made up of nucleotides and from nucleotides we use very specific molecules that we can add into them that we can use to make nucleotides to incorporate into the dna or incorporate into rna there's this molecule here called paraminal benzoic acid and para aminobenzoic acid is actually converted into something called dihydrofolate and then tetrahydrofolate and that's usually incorporated into particular types of like thymine nucleotides so it's important to incorporate into dna and into rna particularly is a nucleotide like thymine now if i give a particular drug right dapzone what dapzone will do is dapsone will actually inhibit the particular enzymes involved in converting paraminal benzoic acid into dihydrofolate so it's involved in the metabolic pathway here so it'll inhibit this particular step when it inhibits the conversion of perimenobenzoic acid into dihydrofoliate that means you get less of this less of this and less incorporation into dna and rna less of the actual nucleotides to make dna to make rna and that is important because we don't have that we can't actually have the nucleic acids that we need to code for replication and transcription processes pretty straightforward all right so we got rifamycins which is inhibiting the rna polymerases dapsone which is inhibiting the metabolic pathway that makes nucleotides via the perimenobenzoic acid pathway the next one that i want you guys to remember is streptomycin now streptomycin's actually pretty cool streptomycin is a kind of a second line agent that you can use in like tb infections but what streptomycin will do is it inhibits a very specific component here so you know how we need mrna to interact with the ribosome specifically there's the two components the 30s and the 50s ribosomal subunit streptomycin will bind to the 30s ribosomal subunit and inhibit it from being able to interact with the rna and make proteins so if you inhibit the 30s ribosomal subunit what do you do to the actual protein synthesis you decrease protein synthesis so again i want you to remember streptomycin inhibits the 30s ribosomal subunit rifle mices inhibits the rna polymerase enzyme and dapsone inhibits the paraminal benzoic acid pathway leading to less tetrahydrofolate less nucleotides that are needed in dna and rna all right the next thing here is isoniazid now this one is a little bit kind of a complicated pathway i'm going to try to dumb it down a little bit but what happens is isoniazid gets taken up into this actual myobacterial cell when it gets taken up into the mycobacterial cell it's converted into like a metabolite kind of an active metabolite we're just going to kind of draw like little asterises on this because now it's activated in order for it to be activated there's a very specific enzyme that performs that function to activate it once it's brought into the mycobacterium and this is called catalase peroxidase also known as cat g enzyme and what this does is it activates the isoniazid into this active metabolite all right once it's in this active metabolite form it then binds with another molecule that's present inside of the actual mycobacterium and this molecule is called nad so it'll bind with nad so then we get kind of this active metabolite of isoniazid plus we have bound to it the nad molecule once you have this this molecule is very interesting because of what it can do is it finds a little enzyme here you see this this enzyme right here this enzyme is called enol reductase and what enol reductase does is is it helps to be able to stimulate the production of particular molecules that are integral into the cell wall and obviously the cell wall is important for resisting osmotic forces if you don't have the integral component of it you aren't able to resist osmotic forces and the actual bacterial cell will die what is that particular component that it makes well let's actually say that we take a slice of the cell wall out and zoom in on it there's different types of molecules that are integral to the actual cell wall and this would be from the outer portion all the way to the inner portion so outer to enter that inner layer here is going to be the inner cell membrane so this would be your cell membrane as the innermost layer so your phospholipid bilayer then after that in this pink layer this is your peptidoglycan layer this is your peptidoglycan layer then after that in this maroon color here we have something called arabinogalactin arabino galactan so kind of like a sugar molecule kind of like a polysaccharide molecule then you have this fatty acid layer called mycolic acid so mycolic acid very important component and on the outermost layer here in red you have your glycolipid layer now what's really really important is enol reductase helps to be able to synthesize the mycolic acid molecules which are integral to the cell wall whenever you give them isoniazid it gets converted into this metabolite binds with nad and now when it binds with nad and it's in the activated form it can then inhibit the enol reductase if we inhibit the enol reductase we then reduce the synthesis of mycolic acid if we reduce the synthesis of metalic acid we lose an integral component of the cell wall and the bacteria and then subsequently die so that's isoniazid i know it's a little bit complicated but i hope that pathway makes it a little bit more simplified all right to go along with my colic acid there's another particular drug we didn't completely know how this enzyme or this drug actually worked it's still questionable but what we know is that this drug here called pyrazinamide works to inhibit mycolic acid formation and so there was questions of how exactly does it some of the most recent literature says that it inhibits a very specific enzyme and this enzyme is called fatty acid synthase and mycolic acid is kind of like a fatty acid so if you don't have this enzyme guess what this enzyme actually does it helps to be able to synthesize the very important molecule that we incorporate into the cell wall what do you think it is glycolic acid so if we inhibit this enzyme we use paraxinamide we inhibit the actual fatty acid synthase can we make the mycolic acid molecules that are integral to the actual cell wall no so we'll decrease the actual synthesis of mycolic acid molecules so two drugs will inhibit mycolic acid one is isoniazid through this kind of complex pathway and the other one is pyrazinamide which inhibits the fatty acid synthase so fatty acid synthesis parasitimide enol reductase inhibition isonia is it okay we're almost done last one here ethan butyl is another interesting one so remember i told you that there was two important components here to the actual cell wall mycolic acid is a big one that i want you to remember and then this maroon color one here is the arabinoglactin this is another important layer that i want you to remember this enzyme here is called arabinus oil transferase like what the heck this enzyme here is called arabinosoil transferase and what this enzyme does is is it takes particular like sugar molecules that are present inside of the bacteria the two sugar molecules that you actually would need to remember one is called arabinose and the other one is called galactose what it'll do is it'll take a combination of these molecules utilize them and then convert them into arabinogalactin okay which is integral into making this particular molecule here that it's important corporate into the cell wall so it'll use these molecules and make this thing called arabinoglactin that's what the job of this enzyme is if i give this drug called ethambutol ethambutol will inhibit the arabinosial transferase if i inhibit arabinosial transference i can't take arabinose and galactose and make arabinoglactin if i can't make arabinogalactin do i have the integrity of the actual cell wall no i lose my integrity therefore the actual bacterial cell is susceptible to death so to quickly recap these rifamycins inhibits rna polymerases streptomycin inhibits the 30s ribosomal subunit daphzone inhibits the paba pathway which inhibits nucleotide formation isoniazid inhibits fatty acid synthesis particularly of mycolic acid by inhibiting enol reductase pyrazinamide inhibits mycolic acid formation by inhibiting fatty acid synthase and ethane butyl inhibits arabinoglactin formation by inhibiting arabinosol transferase i know it was a lot slightly complicated i apologize but i hope this makes sense now let's move on to the actual indications of these drugs we're going to talk about what are the actual clinical usages it's actually straightforward so mycobacterium tuberculosis we're not going to go through the entire pathophys and all the clinical features of tb we'll talk about that when we dedicate an actual lecture to tuberculosis and all these other ones but when we talk about tuberculosis obviously we know it's due to the bacterium mycobacterium tuberculosis now obviously that that area love that bacterium loves the lung so it loves to kind of stay interact with macrophages and cause these types of nasty lesions as you can see within the lungs and then the problem is once it actually causes these lesions typically within the upper lobes of the lungs what happens is it has the ability of so actually if someone's severely immunosuppressed for some reason it can disseminate and spread to other organs of the body where it can spread to the actual brain causing like meningitis or encephalitis spread to the actual bones where can cause osteomyelitis spread to the adrenals where can cause adrenal failure spread to the liver cause liver failure spread to the actual lymph nodes causing like lymphadenopathy or scrofila so a lot of things that can happen when you have this infection but the question is sometimes people can be infected with tb never know it not have any idea but when we do like the tubercular skin test the ppd test and we see that the bump is maybe a particular size but they don't have any active infection going on but they have maybe the latent infection of tb we can treat them for that now if they have the full-blown active infection where it's involving the lungs or it's disseminating then we have an active tb treatment we should know what are the agents that we utilize in the latent and what are the ones that we utilize in the active infection so in the latent tb where they're not actually having active pneumonia infection they're not disseminating into the actual systemic vasculature in other parts of the body we utilize two particular drugs that we can uh use here one or the other so one is you can use isoniazid commonly abbreviated inh just get used to that one i might still use that sometimes so inh we can do this for about six to nine months some literature will say six months some will say nine months it depends upon how frequently you take it the other one we can utilize is rifampin so rifampin would be the other option we could utilize and we could use that one for four months so if a patient has latent tb they test positive or they have a particular size of the tuberculin skin test we can put them on one of these two drugs for that time duration now if they have active tb they actually have active like casein granulomas with inside of the lungs or they have gone complexes or they have ranky complexes so they have dissemination to other areas of the body they have active tb we treat them a little bit differently we utilize what's called a ripe regimen i think that sounds crazy but you start off first with what's called the ripe regimen so this is rifampin isoniazid piracinamide and ethambutol so you utilize these four drugs first for at least two months okay after the two months are up you then move into the second part of the regimen which you utilize rifampin and isoniazid for four months so it always works in this particular fashion for the first two months you use the ripe drugs rifampin isoniazipiers and ethambutol for the second part of the regiment for the next four months you use rifampin and isoniazid when you have a patient on isoniazid one of the common adverse effects is b6 deficiency which can cause neuropathy it can cause anemia it can even increase the risk of seizures so because of that we want to be able to give the patient b6 so we give them b6 supplements to be able to augment that and prevent them from developing b6 deficiency because of isoniazid now if a patient has active tuberculosis and it's actually seeding it's spreading so they have like miliary tb they have tb meningitis oftentimes we may add on streptomycin as a second line agent but generally when you're at this point you're going to seek the id consult because they're going to be way too sick for you to be able to have to figure this out you'll see got an actual infectious disease specialist and they'll be able to kind of figure out what is best in this situation so what i think is the most important remember is what are the two drugs that we can utilize in latent tb what are the length of the duration then active tb what are the actual regimen ripe and then rifampin and inh two months for the ripe four months for the rifampin and inh add b6 it's very important sometimes you can add streptomycin or other particular drugs into this regimen if they have more systemic or refractory tb all right so the next one here is mycobacterium leprade so leprosy so in this one i can't say that you'll oft didn't see this very often but and it's a mycobacterium so we should know the particular agents that we utilize for this in the same way that we know tuberculosis so typically it loves to involve the skin so it likes to cause like these hypopigmented skin lesions that's one particular thing so you may see particular skin lesions and then the other thing is you actually may see nerve palsies so it typically likes to cause like thickening of the nerves and when it thickens up the nerves it actually may get compression of particular areas one of the common areas is like the ulnar nerve so you may see like an ulnar nerve palsy that might be one um and then the other one is the peroneal nerve so you actually may see a peroneal nerve palsy in these wells uh situations as well so that would be the particular thing to think about now if somebody does have leprosy one of the particular agents that'll be utilizing this it's often two particular drugs dapsone and rifampin so i want you guys to remember dapzone and rifampin sometimes we may add another dragon called clefazamine but generally that's if they have like what's called the tuberculoid form of leprosy so i don't want to go too far down that road remember daphzone rivampin for lepre remember these isolized there for six to nine months for leighton tb refamped for four months for latent tb active is right for two months reframing high nh for four months and then add on your b6 the last mycobacterium infection that i want to talk about is called a mac so it's called mycobacterium avium intracellular complex infections let's talk about that so with mycobacterium avium intracellular complex infections generally these love to cause like these like fiber cavitary like pneumonia so we're obviously gonna see like some type of pneumonia like generally some type of like nodular fibrocavitary lesion what can happen is in certain situations this can actually disseminate especially in immunosuppressed individuals spread to the liver spread to the actual bone marrow and even spread to the spleen in situations where a patient tests positive from mycobacterium-avium intracellular complex what do you treat them with it's usually particularly like a three-part combination so you're going to utilize one drug is called ethambutol you guys remember that one and then we'll add on another drug to that and we usually utilize what's called rifampin so we'll add rifampin as another one that we can utilize and then the last one here is we add something called a macrolide we talked about this in the antibiotic section but this would be particularly like your clarithromycin or azithromycin the next thing to potentially consider is the plus or minuses when will we add other particular agents on so these are the primary agents that we're going to utilize in the mac infection but we may add on things like aminoglycosides you may add on things like fluoroquinolones particularly in those severe or refractory cases severe slash refractory cases but that would be the particular thing that i want to want you guys to remember for the mycobacterium avium intracellular complex infections you always start with ethambutol rifampin and a macrolide plus or minus an aminoglycoside or fluoroquinolone in the severe refractory cases one thing to add to these actual things here is that any time you're actually giving somebody rifampin so i would add this as an extra little side note in case they ask you this on the exam if a patient is hiv positive and they are going to be on rifampin if you put them on rifampin whether that be for mycobacterium leopard whether that be for tuberculosis or whether that be for mycobacterium avium intracellular complex because rifampin can interact with the cyp 450 system you might want to switch to rifabutin so this may be a question that they ask on the exam because there is less interaction with the nrtis and that is extremely important because remember when we treat hiv we use nrtis or in rtis or protease inhibitors all those different drugs well if you give someone rifampin or phampin may actually decrease the concentration of these nrtis in an rts but if you give them rifabutin there is no actual cytochrome p450 inhibition with this one so less effect on the nrtis and rtis protease inhibitors all those things so that's really really important to remember so hiv positive patient that you're putting on rifampin switch them to rifabutin because there's less kind of like drug interactions there all right now that we've talked about that let's hit the adverse reactions all right so let's talk about the adverse effects of these antibiotic bacterial drugs so first thing rifampin what do we need to know about this one first thing is that they will ask you this on the exam patient comes in they're freaking out because they have red orange urine that's a completely normal harmless adverse effect of rifampin but just be aware it is an adverse effect and i would probably let the patient know that before they go you know home okay so watch out for any kind of like red orange urine it's completely harmless but just let them know that so they don't have like a heart attack okay then the other thing here is that it can actually cause false positive urine opiate tests i just thought that was an interesting thing to potentially know so false positive urine opiates but i think the other big thing to remember here is the effect on the cyp 450 system remember i told you it acts as an inducer so because of that if you give this it's going to decrease the concentration of a particular drug that you're taking it with that's why if a patient is hiv positive they're taking nrtis or nrtis or produce inhibitors if you give that with rifampin it can actually decrease the concentration of that drug because it is a cyp 450 inducer so it's important to be able to remember that when you put them on rifampin watch out for any other drugs that they're taking with all right pyrazinamide what's the important thing to remember for this one monitor those lfts some people would say rifampin is hepatotoxic it is a very minor minor minor hepatotoxicity it's important to train the lfts but it's significantly less the patatoxic in comparison to all these other ones so perizenomide is the big one that i would remember is hepatotoxic this one is isoniazid so hepatotoxicity watch for the bump in the lfts so watch for any kinds of hepatotoxicity next thing here with pyrazinamide it plays a particular role within the uric acid so it may actually reduce the uric acid in the actual urine and increase the uric acid inside of the blood and so this is called hyperuricemia so it may increase the uric acid in the blood causing hyperuricemia so if a patient is actually in the vignette and they say okay putting them on piracinamide but they have a history of gout what should you potentially watch out for worse exacerbations of their gap because you're going to increase the uric acid levels increase uric acid crystal formation and they can deposit into that big toe and then they come in my toes all jacked up so important to remember that with the perizonamide ethan butyl what is the important thing to remember for this one it affects the eye particularly the optic nerve so this can actually cause optic neuritis important remember that they may have visual disturbances and decreased visual acuity so optic neuritis whenever you put this medication on somebody watch out for any types of visual dysfunction maybe follow up with the optometrist or ophthalmologist all right so rifampin red orange gear and false positive urine screens this is the big one cyp 450 inducer piracinamide apatotoxic hyperuricemia watch out and gout ethambutol optic neuritis consider doing like follow up with the actual ophthalmologist or particularly optometry daphzone if you put somebody on dapzone what should you potentially watch out for one of the big things is it can actually oxidize the hemoglobin and convert it into the ferric form whenever that does that you can't bind oxygen so oxygen won't be able to bind with dyspheric form this oxidized form and because of that they can cause hypoxia more of like a cytotoxic or histotoxic epoxy and this is actually called met hemoglobinemia [Music] watch out for this one the other thing is if a patient has a g6 pdh deficiency and you give them dapzone it can increase their hemolytic events and so it may cause an acute hemolysis event and that's an important thing to remember along with like nitrofran tone and fluoroquinolones and and bacterium and things like that the other thing is it can actually suppress the production of particular white blood cells such as neutrophils so it may actually cause a neutropenia all right so big thing to watch out for again met hemoglobinemia g6pdh deficiency if they have that and you give them this drug it can cause an acute hemolytic crisis and neutropenia at the butyl optic neuritis paraxinamide hypererosimia paddle toxicity rifampin watch out for the cyp450 induction all right let's come down isoniazid and streptomycin alright isoniazid what do we got to remember about this bad boy this one actually will cause some injury to the liver so watch out for the bump in the lfts you should monitor that when you have the patient on isometize it or what else piercing life not so much with the rifampin though remember that the other thing here's what's really interesting it can actually cause an anion gap metabolic acidosis through two ways so we can cause an anion gap metabolic acidosis by bumping your beta hydroxybutyrate do you remember what that is that's a ketone body so it may cause a ketoacidosis because of it causing an increased acetyl-coa metabolism or increase through the acetyl-coa pathway and it also can increase your lactate so it may cause a lactic acidosis and a ketoacidosis as a particular cause of their anion gap metabolic acidosis the other thing is it can cause a drug-induced lupus you're like what the heck it's important to actually remember this because especially in your exams especially in the step one they may ask you what are the particular drugs to remember that can cause drug-induced lupus and this is one of them isonisa but you can remember this by the ship mnemonic sulfa drugs hydralazine isoniazid procainamide and phenotone just remember this because they can come up on your exam the next thing is it can cause a b6 deficiency now b6 deficiency can do two things one of the things with the b6 deficiency is it may alter the myelination of particular neurons and lead to neuropathy so watch out for any types of peripheral neuropathy the other thing is it can also alter the activity of particular enzymes inside of the actual red blood cell or alter the ability to make red blood cells and this can lead to anemia whether this is like a aplastic anemia or a citroblastic enemy it can drop your red blood cells the other thing is it can actually cause seizures so it may actually reduce your seizure threshold and these can actually be refractory so you can actually give a patient like multiple benzos if they're in status epilepticus and it'll not work so watch out for any refractory to benzos in patients who have a b6 deficiency you give them some b6 they actually might start responding to some of the benzos okay so isonize it watch for a pad of toxicity watch the anion gap for any metabolic acidosis watch for drug induced lupus remember the mnemonic and then seizures refractory to benzos and then with b6 deficiency you can particularly see anemia and neuropathy last one here is your streptomycin remember that's that second line in your mycobacterium tuberculosis we know it's not a part of the right regimen it's not a part of the second part for the four months afterwards it's more of the add-on for like miliary tb or more of your tb meningitis and these ones it's important where it's an aminoglycoside you know glycosides are nephrotoxic they will jack those kidneys up so watch for any signs of nephrotoxicity so monitor their creatinine monitor their bun their urine output the other thing is it can actually really hurt their inner ear causing ototoxicity particularly can actually hit the uh eighth cranial nerve right so particularly watch out for the vestibular cochlear nerves watch out for any oto toxicity and it also can affect the growth of the baby so it's important to remember that it's teratogenic tyradogenic is a big one here so avoid this in patients who are pregnant and then the last thing is you want to be careful if you give this to a patient who has a history of myasthenia gravis it should be contraindicated in what's called myasthenia gravis someone but mg the reason why is it alters with the actual uh response of the antibodies that actually bind at the particularly at the nicotinic receptor on the muscle cells and so this may alter that in a particular way so it's important to remember do not give this in patients who have myasthenia gravis do not give this to patients who are pregnant and watch the actual renal function and again watch for any kind of changes in their hearing when you put a patient on tryptomycin all right my friends you think we're done but we gotta review this we gotta we gotta anchor this stuff into our cerebral cortex so let's do some cases and see if we can actually anchor this stuff into our cerebrum all right so let's do some practice problems or kind of like really understand what we talked about here on the white board so you're performing rounds you're with your infectious disease and they say okay i'm going to ask you some questions about their mechanism of action let's see if you guys can pick out which drug it is based upon what i'm kind of prefacing you with so first one is which drug inhibits the rna polymerase so this cute little enzyme here that takes dna makes rna and helps to be able to synthesize particular types of bacterial proteins this would be your rifamycins right so your rifampin rifabutin things of that nature next one is which one of the drugs actually inhibits the 30s ribosomal subunit inhibiting protein synthesis that are needed in the bacteria this would be streptomycin great which one of these drugs actually works to inhibit the arabinosial transferase which takes a rabbinos and galactose and makes arabinol arabinoglactin which is an important component of the actual cell wall you guys know this would be which particular structures come on let's see if you guys remember this one come on this is the ethambutol so ethan butyl which drugs actually inhibit the fatty acid synthase that takes particular like fatty acids and helps to be able to make what's called mycolic acid which is an important component of the actual cell wall this would be paraxinamide which of the particular drugs helps to be able to inhibit the enzyme that actually helps to convert what's called the perimenobenzoic acid into dihydrofolate and then subsequently tetrahydrofolate which is needed to be able to make nucleotides to incorporate into the dna this would be which particular drug do you guys remember dapsone right okay good next one is which one of the drugs is actually going to be taken into the fungal cell acted on by the catalyst catalase peroxidase and whenever that happens it turns it into an inactive and it turns from an inactive into a very active type of molecule there it binds with nad and when it binds with nad this molecule here actually can inhibit enol reductase and what that does is it decreases the synthesis of mycolic acid in the cell wall this is going to be isoniazid all right great so we covered all of these particular drugs okay next question is this patient has latent tuberculosis what are the particular treatment options for those with latent tb you guys remember that we always can consider two options one is we can do isoniazid for about six to nine months right or refamping for about four months the next question is you have a patient with active tuberculosis if they have active tuberculosis you always do the ripe regimen so rifampin isoniazid paraxinamide and ethambutol for two months then you subsequently follow after that with rifampin and isoniazid for four months and add on b6 because b6 is important because if you're taking isoniazid that can actually cause a b6 deficiency and lead to neuropathy and seizures etc so it's important to remember that the other thing is if a patient is hiv positive and also has active tb or a latent tb you should consider switching rifampin to rifabutin and the reason why is rifampin can actually act at that cytochrome p450 system and when you give rifabutin it doesn't actually have to have as much interaction with the cyp 450 system because what can happen is is rifampin is a cyp450 what's called inducer and because it's actually acting as an inducer it decreases the concentration of the particular drug that's being metabolized by the cyp450 system and that in patients who are taking hiv medications like nrtis it would decrease the efficacy of those drugs or the concentration of those drugs so that's why you switch to rifabutin because it's not an inducer and if they have tb meningitis or miliary meningitis you really seek infectious disease expertise but you can consider adding on streptomycin all right another patient has what's called the mac infection so mycobacterium avm intracellular infection what are the particular treatment options because this is another type of mycobacteria so we can actually consider treating these patients with what we can do rifampin or also known as rifabutin if they have hiv we can also consider ethambutol and then lastly we can add on a macrolide like a zithromycin okay now if they have severe refractory cases you can add on something like a fluoroquinolone or an aminoglycoside so again ethambutol rifampin and a macrolide for a mac infection and the big ones to remember here is that ethan butyl is a part of that that triad and rifampin is a part of that so again for latent tb isoniazid 69 months or a fampen for four months if it's active it's going to be the ripe for two months and then after rifampin isolized it for four months add b6 can switch to rifabutin if they have hiv okay add streptomycin refractory or miliary types of tb or what's called menin tuberculosis meningitis if it's a mac ethan butyl rifampin and macrolite add-on aminoglycosides and fluoroquinolones in refractory cases all right you have another person who has another mycobacterial infection called mycobacterium leprate which is leprosy if they have leprosy this obviously causes these hypopigmented and nasty skin lesions and this can also lead to nerve palsy it thickens the nerve which can actually cause compression of the ulnar of the peroneal nerve and this can cause a lot of problems there as well so we treat these patients with dapzone and rifampin dapzone and rifampin you can add on clefazamine and tuberculoid leprosy so rifampin dapzone mycobacterium lepre ethambutol rifampin macrolide and mycobacterium avium intracellular rifampin for four months isoniazid for six to nine months in latent ripe for two rifampin isoniazid for four if it's active tb switch rifampin to rifabutin if any patient has hiv because it can reduce the efficacy of the nrtis all right boom now the next thing that we have to think about is what are the adverse drug reactions so a big thing to think about here is we talked about all of these already and what they're treating but let's start off with the rifamycins first what i want you guys to remember especially with rafam but it can cause red orange urine and this is actually completely harmless it's just something to think about if a patient starts kind of getting really scared the other thing is it can actually cause a false positive urine opiates so if someone's actually getting drug screened remember it can potentially cause a false positive the other thing it's what's called rifampin it's a cyp-450 inducer meaning that it can actually work to actually increase the activity of the cytochrome p450 metabolism which will decrease the concentration of the drug all right so those are big things to remember the next one that we should talk about here is going to be isoniazid this is the big one it's really it actually hepatotoxic so you should be monitoring patients lfts and it can also produce what's called a metabolic acidosis it can actually increase the production of ketone bodies and it can actually increase the production of lactate so watch out for any metabolic acidosis that have an anion gap that's elevated the other thing is it can actually suppress the bone marrow and potentially lead to anemia one of the ways that we think this is actually maybe citroblastic anemia by due to the b6 deficiency and then the other thing is it can actually cause drug induced lupus remember the mnemonic ship right so we said sulfa drugs hydrolyzing isoniazid and then we also have phenetoin and procainamide and remember it can also cause seizures it can lower the seizure threshold whenever patients have b6 deficiency having them become refractory to benzodiazepines and it can also cause neuropathy all right pirazinomide we said this is also hepatotoxic so watch those lfts and it can also increase the uric acid so watch out for this in patients who have gout and then butyl can cause optic neuritis so it can cause changes in their vision to make sure that they're getting annual eye exams if they're on this drug and then we have a patient who's on dapsone for again what was that for leprosy we can actually watch out for any met hemoglobin anemia a g6pdh deficiency that can actually if they take it uh this and they have that underlying disease it can actually cause an acute hemolytic crisis which causes severe anemia and then watch out for neutropenia okay and then we also have streptomycin which any aminoglycoside within this category is nephrotoxic ototoxic teratogenic as well and then again can be contraindicated in mycenae graphics because it can worsen the myocena gravis alright engineers that covers the anti-microbacterials i hope it made sense i hope that you guys enjoyed it as always until next time [Music] [Music] you

Channel: Ninja Nerd

Views: 138,665

Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science

Id: 4PSTbkFT2Vw

Length: 36min 12sec (2172 seconds)

Published: Fri Jul 15 2022