p450 enzymes are actually incredibly high yield for usmle and comlex i want to start this video by talking about the different p450 inducers and inhibitors i'll list all the drugs explain the pathophysiology of what happens to affect drug metabolism and then we'll wrap up the video by talking about the specific subtypes of the p450 receptors which has become a very annoying topic to memorize of course i'll give you my mnemonics along the way as we go through the normal physiology and we'll wrap up by doing a summary of everything that you need to know so when we talk about p450 enzymes it's probably best to start by talking about certain drugs that act on the enzymes now certain drugs can either be inducers of p450 or they can be inhibitors of p450 so we're not talking about the enzyme itself right i'm not saying that the p450 enzyme is the inducer or is the inhibitor what i'm actually saying is that certain drugs induce p450 or certain drugs inhibit p450 so let's start by listing out the drugs that act as inducers of p450 enzymes those drugs are seen here carbamazepine rifampin alcohol phenytoin gryzofulvin phenobarbital and sulfonylurea so all of these drugs are p450 enzyme inducers so what does that actually mean well let's talk about the normal physiology and pharm pharmacology here so normally you have this drug and the drug over time interacts with a p450 enzyme so under normal circumstances that over time you take the drug and eventually the drug needs to be broken down so when the drug is reaching its half-life and starting to be metabolized that p450 enzyme will work its way toward the drug will latch on to the drug and then will basically destroy the drug by metabolizing it and this is all a normal process drugs have to be eliminated and metabolized by our body and that's done by enzymes so that drug disappears and you're left with the p450 enzyme which can then go and find other molecules in the body to keep on breaking down so that is the p450 system now let's go back to this slide what happens when you put a inducer of p450 into the equation so the inducer is shown here in green so this could be any one of those drugs that we just listed right carbamazepine rifampin alcohol phenytoin graisofulvin uh phenobarbital or sulfonylureas any one of those drugs if you take them will have an effect on p450s ability to metabolize other drugs so what this does is it speeds up this process because it's an inducer of p450 so when p450 isn't around to normally metabolize these drugs but you take an inducer of p450 so you take one of those other drugs that i listed on on the previous slide p450 shows up faster and accelerates toward the drug metabolizes the drug and destroys the drug so what i'm saying here is that a p450 enzyme actually induces p450 to or excuse me a p450 inducer induces p450 as the name suggests so usually the enzyme is not going to metabolize the drug until later on in the day let's say but when you take an inducer you make p450 show up faster metabolize the drug faster and get rid of some other drug faster so inducers of p450 in a nutshell here they increase drug metabolism so you have to be careful because if you're taking some other medication and all of a sudden you start taking in addition to that other medication you start taking something like phenytoin phenytoin induces p450 which breaks down that other medication that you normally take and therefore that other medication doesn't do its job because it's getting broken down early because you're inducing p450 to break down that other drug so that's how the p450 inducers work now let's switch gears and talk about the p450 inhibitors so i listed them out here for you valproic acid aka valproate ketoconazole isoniazid sulfonamides chloramphenicol amiodarone erythromycin and i want to say with erythromycin it's it's really all of the macrolides with the exception of azithromycin quinidine and grapefruit juice so let's talk about the the pharmacology and the physiology of the inhibitors so again normally you have some other drug in in your body that you normally take over time it needs to get broken down it'll go through its normal half-life it'll get metabolized the p450 enzyme will associate with the drug it will metabolize the drug and the drug will be broken down but what happens when you introduce a second drug aka a p450 inducer so shown here in red is our p450 inhibitor excuse me i said inducer but i meant to say inhibitor so the p450 inhibitor which is any one of those drugs that i just listed on the previous slide inhibits p450 so normally p450 wants to go and metabolize the drug but a p450 inhibitor will inhibit the p450 enzyme so it literally sits right on top of the enzyme and prevents it from doing its job that enzyme goes away and instead of normally metabolizing the other drug shown in blue on the slide that other drugs showed in blue will actually have a super therapeutic effect or a super therapeutic effect because the p450 inhibitor is inhibiting the enzyme that normally breaks down the other drug so this will decrease drug metabolism and basically this can cause toxicity or build up of the drug that needs to be normally broken down so p450 inhibitors cause drug toxicity by building up drug effects because they decrease drug metabolism and p450 inducers do not cause drug toxicity but they cause a sub-therapeutic effect because they increase drug metabolism and therefore there's no drug around to actually carry out its effect so those are the differences the big picture differences between the inducers and the inhibitors what's really important for you when you're taking us emily and comlex is to know which drugs are inducers and which drugs are inhibitors now of course this is a very long list and there's no easy way to memorize this oh but there is i'm going to give you my mnemonic to remember the p450 inducers so if you look at the first letter here i've bolded them and put them in red the mnemonic is crap gps induces my rage so i don't know if you guys remember before iphones had the gps on them everybody used to use like their garmin or their tomtom they used the gps but if you were ever driving with your gps and it couldn't calculate the map fast enough or was just buffering that was the most rage inducing thing of my life i did that so crap gps crap gps corresponds to the letters of the drugs that are inducers so they induce my rage if you can look at this list and know what the inducers are then by process of elimination you'll know what the inhibitors are so i never ever memorized the inhibitors but i just memorized the inducers using my mnemonic and then on test day if i got some question where it was very clear they were asking me about either an inhibitor or an inducer if it wasn't one of the crap gps drugs then i knew it was an inhibitor and therefore i knew it was inhibiting p450 and you know i would work that out in my head to figure out what the answer was but you you literally cannot go wrong if you know this mnemonic so crap gps induces my rage carbamazepine rifampin alcohol phenytoin gryzovolev and fetal barb and sulfonylureas they all induce p450 which means p450 shows up and breaks down the other drugs faster so the other drugs don't have as big of an effect that's all of the induction and then in inhibition of p450 is just the complete opposite and you'll know those drugs by process of elimination so what i would say is take some time to just stare at this slide and know what the inhibitors are so know that ketoconazole and valproate and sulfonamides and chloramphenicol are either inducers or inhibitors and then if you get a question in your head use the crap gps induces my rage mnemonic to figure out which one it is and just use process of elimination i've done this my whole life in medicine and it's never been a problem for me so this is how i suggest you attack these questions they're really really high yield questions and this will help you out big time so now we're going to talk about the actual subtypes of the p450 enzyme system so in recent years on us emily and complex they've started to ask you about these subtypes which sucks because like look at these things cyp 182 cyp 2e3 2 c9 2d6 3a4 and what drugs these specific subtypes actually metabolize so there was really no easy way to do this and when i was a medical student what i did was i came up with mnemonics for these because i didn't want to lose these points on test day because as as stupid as the question is it's still free points if you take a little bit of time and come up with some beautiful mnemonics so let's start by talking about these one at a time we'll go just top down uh first i'll tell you the drug that the subtype metabolizes and then i'll give you a beautiful mnemonic to remember it so you get free points on test day so cyp182 metabolizes acetaminophen aka tylenol so the way that i remember this is i rewrite the word acetaminophen and i capitalize the a's so as a c menophane and this is one word with two a's aka one a two one word with two a's aka one a two so one a two acetaminophen um the mnemonic for a lot of these is just reorganizing the mnemonic with the letters and the numbers so acetaminophen is one big word with two a's aka 1a2 so cyp182 is a p450 subtype that metabolizes acetaminophen pretty easy right that took what 30 seconds and now you have a free point on test day all right uh cyp2e3 this metabolizes ethanol aka alcohol so this one's super easy guys you have to be 21 to drink ethanol so 2 1 and the e we just reorganize that into 2e1 so you have to be 21 to drink uh ethanol aka alcohol so that's 2e1 so the 2e1 subtype metabolizes alcohol we are about 60 seconds in and you've already got two free points on test day which means you can match whatever specialty you want because you're learning things that your colleagues are not so let's keep this rolling uh cyp2c9 this is going to metabolize warfarin aka coumadin so like the prototypical blood thinner that's used in the hospital how do we remember this so this this is a kind of like a two-part mnemonic so part of this requires your knowledge of knowing which factors coumadin and warfarin act on so if if you recall warfarin aka coumadin acts on factors 2 7 9 10 protein c and protein s and how this demonic works is you just go every other factor in order you put an arrow at them and we've got the warfarin factors and is it any coincidence that 29c aka 2c9 is the subtype of the p450 system we're talking about so you list out the factors that warfarin acts on you pick every other factor in ascending order and you rearrange them so instead of 29c it's 2c9 so cyp2c9 affects warfarin factors 2c and 9 aka it metabolizes warfarin so we're rolling easy right guys you're getting free points let's keep going uh cyp2d6 is gonna metabolize your cardiovascular drug so i'm just gonna keep this really broad to help you if you're on your test and they ask you a question about which subtype metabolizes which drug and the drug is a cardiovascular drug pick 2d6 just it's just worth the guess because most of the time you're going to be right so how do you remember this well an echocardiogram is also known as a 2d echo so the only subtype receptor with 2d in the name is 2d6 so therefore cyp2d6 is going to be your metabolizer of cardiovascular drugs aka 2d echo is our mnemonic so 2d echo for 2d6 2d echo reminds us of an echocardiogram which of course is a cardio you know cardiology thing so cardiovascular drugs are metabolized by 2d6 we're going to wrap up with 3a4 this one there's really no mnemonic for it because 3a4 is the most ubiquitous p450 subtype so if you have a drug that's not acetaminophen that's not alcohol that's not warfarin and that's not a cardiovascular drug you guess 3a4 because it's the most common it's like i think it metabolizes up to something like 60 of all of the the drugs so if it's not one of the first four that fits the first four mnemonic by process of elimination you guess 3a4 and you're going to be right 60 of the time so guys that's it that's the p450 enzyme subtypes we've talked about them here 1a2 2e3 2c9 2d6 and 3a4 four beautiful sexy mnemonics we talked about p450 inhibitors and p450 inducers remember when we say inhibitor we're talking about what the drug does to the enzyme so an inhibitor of p450 will block p450 therefore p450 cannot go on to break down other drugs and therefore other drugs will build up p450 inducers will induce p450 aka it'll be like yo p450 come on bro i need you around here and then it'll show up and p450 will go on to break down other drugs inappropriately so other drugs will have a sub therapeutic effect that's the summary i really hope that this was useful remember p450 is really high yield so spend some time with this video watch it once or twice and let me know in the comment section if this was helpful for you