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these are all really good and important things to be aware of and I recommend gathering that info for any new meds. i don't say this to like, blame people who were not given this info by their doctors and who took meds without being given this information, but rather to give people resources for being more in control of their own medical treatment going forward 💜

CYP450 is a family of enzymes in humans. enzymes are chemicals that speed up chemical reactions; in this case, in our bodies, CYP450 enzymes process the vast majority of currently available medications. because of that, they're responsible for most drug interactions.

different substances - including medications, supplements, and even foods - can affect the CYP enzymes in different ways.

a CYP inhibitor blocks the CYP enzymes from working to process the medication. that means you can end up with more of the medication in your body than you expect. that can cause mild, moderate, or severe side effects. good examples of CYP inhibitors are St. John's wort, grapefruit, and isoniazid (a tuberculosis medication).

a CYP inducer encourages the CYP enzymes to work faster. that means you can end up with less of the medication in your body than you expect. that medication may not work as well. this can be especially dangerous in cases where, for example, you're suppressing a dangerous effect (like autoimmunity or transplant rejection). some examples of CYP inducers are insulin, tobacco, prednisone, and in some cases, St. John's wort again.

a CYP substrate is just a substance/medication that is affected by an inhibitor or inducer. birth control is a very common substrate, and its effectiveness is affected by many medications.

each substrate is related to a different family of CYP enzymes, like CYP3A4 or CYP2D6. each one responds to different inhibitors and inducers.

you can see why they often don't tell patients this stuff: It is complicated. this is pharmacokinetics! it's difficult stuff. but i really, really believe it's important. knowing how your medications affect each other can save your life. doctors and pharmacists often do not check medication interactions. sometimes it really is up to us to understand what we're putting in our bodies.

at the very least, i urge you to check drug interactions with the drugs.com interaction checker. this checker automates some of the work of cross-referencing CYP relationships. if you have an account, you can save your drug list and cross-check all of your meds at the same time. keep in mind that not all "severe" interactions will necessarily apply to you; i recommend reading the "for professionals" version of the warning to make informed decisions about whether or not you want to be concerned. (this is also something you can discuss with a good doctor if you have the good fortune to have one.)

but, if you have the capacity, at a certain number of medications (i am taking 20+) it really is worth getting to know how they interact with CYP enzymes, what effects you might need to be watching out for (more intense effects from a higher concentration of medication? less intense effects as the medication can't attain high enough concentrations to work as it normally does?), and what meds might be the culprits of new problems as you add more medications.

to cross-check CYP relationships directly, i recommend the flockhart table. search for a medication (ctrl+f helps) and you can see all its documented CYP relationships. (they also have a mobile friendly version, but i find it slightly harder to interpret.)

here's how i do it.

start with a medication or substance. let's say i'm about to start celecoxib (Celebrex), a non-steroidal anti-inflammatory drug (NSAID). on the flockhart table, it's listed as an inhibitor of CYP2D6. (ctrl+f is helpful here.)

think through what the words mean. it's an inhibitor, so it makes the enzymes not work as well. it might increase blood levels of medications that are processed by CYP2D6.

what medications are processed with that enzyme? the flockhart table lists them if you click on the name of the medication you're curious about. CYP2D6 substrates include amitriptyline (Elavil), aripiprazole (Abilify), atomoxetine (Strattera), duloxetine (Cymbalta), oxycodone (Oxycontin), and propranolol, among others.

what effects do i need to be watching for based on the affected medications? for an inhibitor, we're looking for stronger effects; for an inducer, we're looking for weaker effects. let's say i take oxycodone daily. i want to keep an eye on the way i feel when i take oxycodone. am i feeling "higher" than usual? am i feeling dazed or dizzy or numb? or let's say i take propranolol. am i feeling dizzier or more lightheaded? am i having nightmares that i wasn't before?

here's another example. what if i want to check for a substance that might not be listed on the flockhart table? grapefruit is a good example.

wikipedia is actually a great source for this (though in some cases i recommend just searching "[substance] CYP" and seeing what pops up).

head to the list of CYP450 modulators on wikipedia. ctrl+f finds three instances of grapefruit: naringenin (a CYP1A1 inhibitor), generic 'flavonoids' (inhibiting CYP2A6), and bergamottin (a powerful CYP3A4 inhibitor).

think through what the words mean. any substrate medications processed by 1A1, 2A6, or 3A4 enzymes might be dangerously increased in my bloodstream if i consume grapefruit (or anything containing those substances; earl grey tea actually contains bergamottin, too!)

what medications are processed with those enzymes? this i can check on the flockhart table, or i can stay on wikipedia. atorvastatin - a cholesterol medication - is a substrate of 3A4. so is diazepam (Valium). valproic acid, an anti-seizure medication, is a substrate of 2A6. i'm having more trouble finding substrates of 1A1. it's not listed on the flockhart table. there is a paper published that mentions theophylline (an asthma medication) and difloxacine (a fluoroquinolone antibiotic).

what effects do i need to be watching for based on the affected medications? at a glance here, i'd be worried about having too much valium or valproic acid in my system (if i took those meds) - those could have pretty serious effects on my central nervous system. likewise, having too much of that fluoroquinolone antibiotic (if i took it - and i wouldn't, because if you have hEDS you should not take fluoroquinolones unless it's a matter of life or death!) could increase my risk for serious musculoskeletal side effects like tendon rupture. it could also disrupt my bacterial microbiome.

the physician who created the flockhart table, the late dr. david flockhart, was an exemplary physician who truly, truly cared about patients - a rare treasure. everyone's CYP-related genes are different, and it affects the way we respond to medication. we know that, just as we know that CYP relationships can cause serious and harmful drug interactions. but we don't put it into clinical practice. dr. flockhart wanted to change that, and he did pave the way towards that future. we're not there yet. but i do recommend his table.

i hate that this is not something that is widely taught and widely understood. i hate that we have this knowledge about how people metabolize drugs and how drugs work with each other and we often just do not talk about it at all. i hate that i was not instructed on the risks of taking clonazepam (a benzodiazepine, in the same class as Valium) and hydrocodone (Vicodin, an opioid) simultaneously. i experienced central nervous system depression - difficulty breathing, dizziness, confusion, fatigue - multiple times as a teenager before i figured out that i shouldn't take them close together. needless to say, mixing those two drug classes can be extremely dangerous. i got lucky and just felt awful. but at certain doses or under certain circumstances, taking those two simultaneously could kill someone. Does kill people, in fact!

a responsible doctor - one of my favorite doctors! - prescribed me those medications. he just wasn't thinking. it happens all the time.

we should not have to be doing all this work. but often doctors and pharmacists simply do not think about it. and the literature they hand out with medications, while helpful, is not going to cover all possible interactions, especially for polypharmacy patients or people on unusual medications.

likewise, you should know what medications interact with your conditions - like i mentioned fluoroquinolones and hEDS earlier. or how morphine tends to activate mast cells. that's something i can't cover here, though.

However, a tricky detail:

Some medications get affected to the opposite effect by CYP inhibitors or inducers, because they only work after having been metabolised by these enzymes. They're called prodrugs.

So if a prodrug is a CYP3A4 substrate and you take an inhibitor, the amount of active metabolite that actually reaches the body is lower, and the drug might not even reach effective doses. And conversely for combination with inducers.

also, to answer your question in the tags, usamerican pharmacists are required to include prescription handouts with every prescription. the plain language is actually pretty good on these handouts (this is surprising as, typically, legally mandated handouts in usamerica fail to meet any kind of reasonable standard for plain language). However:

it is extremely rare for a patient to actually read this information, the assumption is that it is "the fine print" and therefore not really relevant (many usamericans behave this way about many aspects of their health, it is part of why the public health situation is SO BAD here, the general public has zero relevancy discrimination skills for health information, i don't think there are leading theories on why this is but one of my pet theories is the prevalence of health/medical advertising here. not my area though)

it actually literally is the fine print, the text is extremely small, anyone with any degree of visual impairment is unlikely to be able to read it, and it's never made apparent that this is information you can find elsewhere, just handed over like a receipt (sometimes literally attached to the receipt as though they are equivalent in importance). you are generally not told that you can ask pharmacists about your medications, and if you are there is no framework for what to ask. furthermore no information will be proactively provided, although i have encountered a couple pharmacists who do go out of their way to ask if i have questions. this is an individual choice on the part of people who really care about their job, though. i frequently introduce other usamericans to the concept of drugs.com for the very first time and this is often revelatory, few of them have ever even understood that they have the right to access information about their medications.

usamericans expect that if there will be a problem, their doctor or pharmacist has Secret Ways to catch it for them and will tell them. i overheard my physical therapist telling one of her patients about a month ago that the doctor and the pharmacist have a system that tells them when medications will interact. i have encountered a few systems like this, especially as stopgaps at urgent cares where doctors are very rushed and do not know their patients (though even in those cases they will still actively prescribe things with absolute contraindications, they will just skip past the warnings on their computer screens, this has happened to me multiple times, lol) but for the most part that is not true at all. yet usamericans still largely believe that you don't have to read anything because your doctor/pharmacist will catch any problems.

a lot of information is simply not listed on these handouts. there is definitely no mention of CYP interactions. typically 1-3 medications with very very serious interactions might be listed but otherwise you get a broad "ask your doctor if you have concerns" (your doctor probably won't know and likely won't look it up). under side effects, they will mention seeking emergency care for signs of anaphylaxis and signs of stevens-johnson for meds known to trigger that, and may mention 3-6 "less serious" side effects, but often incredibly common and disabling/distressing side effects are not listed at all (e.g., nightmares or hair loss with propranolol) and typically you need to dig for this stuff on patient boards. i think most side effects are extremely underreported in usamerica because people often don't realize that something COULD be a side effect, again assuming that their doctor or pharmacist knows all of them and will tell them. whereas it is often actually incredibly difficult to get your doctor to agree that something is a side effect (or that you're even experiencing it at all) if they haven't actively read literature on this or been warned by another doctor specifically. some of this is usamerican health literacy skills and some of this is hegemonic medical authority.

if you mean does the prescribing information get handed over, that is not legally required here (at least not in any state i've ever gotten prescriptions from) and typically only gets distributed if the pharmacist is handing you the actual box that the medication was sent to their shelves in, which is relatively rare and usually only for meds where the manufacturer is including specific additional information required for the safe administration of a high-stakes drug (asthma inhalers, biologic injections, epi pens, etc), and the prescribing information is in there kind of as a bonus. (the additional information is mostly to ensure that they do not get sued. most health decisions here are done not for efficacy or safety or public health strategy but to prevent the possibility of lawsuits.)

the prescribing information is also not understandable to most usamericans, including ones with postgraduate educational levels (excluding ones with specific medical education, though to be honest i think at least 65% of the doctors i have encountered here would not be able to comprehend prescribing information in its entirety, but especially not pharmacokinetics). the medical literacy here is extremely bad and there are really no attempts to change this at any level. general literacy here is also very poor, particularly recently.

Well. It only took me HALF A YEAR to answer. Oh my.

So I preordered the game, started my first play through the day it was released and spent a few very nice evenings playing and enjoying it more than I expected. And then my life decided it’s time for me to experience one of the worst nightmares of every illustrator. I badly injured my dominant hand while being right in the middle of an unusually big and time sensitive project. It was quite an interesting period of my life which I would love to forget to be honest.

But! Now my wrist is mostly healed, the scary big project is done and I was able to relax for a while and finish PLZA.

Here’s a few things I was able to draw back in October.

I was ecstatic when I realized I can add a mega alpha houndoom to my team. Sadly I’m no longer able to draw this pokemon normally because once upon a time I decided it would be fun to draw a houndoom based on a borzoi. Borzoidoom is inescapable now.

(I know for sure I’m not the only one who had this reaction)

Also my personal little challenge was to finish the game without fainting once (I’m laughably bad at this new battle system). This is how I failed it:

I eventually caught this gengar, nicknamed him Laventon and added him to my team as a punishment. Despite already having a ghost type.

Words can’t describe my love for mega froslass.

Currently my team looks like this. I won’t accept any criticism, it’s perfect.

(don’t worry about Alakazam he’s fine he’s used to be around ghost and dark types i promise)

And finally. When it comes to the legends games there’s a Volo tax that has to be paid.

You are very unlikely to light yourself on fire.

You are extremely likely to get So Fucked Up, So Fast.

Also! Stress tolerance is such an important skill that having a learning disability in that area is a major symptom of a whole lot of other disabilities/mental illnesses! Struggling with it is a huge part of life! It sucks!

Am I saying everyone with misophonia needs to listen to chewing noises all day? No. But you need to find ways to tolerate it enough that you don't treat others like shit if they make a mouth noise near you.

No, you don't have to read the fic with your trigger tags. But you do need to be able to handle scrolling past the tags without being upset.

It is hard! But not having it also makes you so so so easy to manipulate. That grandma is racist AF because her mom raised her to be uncomfortable around black people and she never fought that discomfort. Trans people make so many cis people uncomfortable and that discomfort turns into bigotry real fast.

i used to work at a Local Organic Produce store that's popular with the lefties in my city who are interested in food justice. i quit for a lot of reasons, mostly the boss, but something i will always remember is one of our suppliers coming in to drop off produce, being told her check wasn't ready, and her laughing and responding it didn't matter -- even a low bank account was more than enough to pay the migrants who picked her produce. i am not filling in any blanks here. she said this.

after quitting, this was a common story i told people about my time there. some then became annoyed at me, acting like i was a wokescold trying to undermine the store's "eco" mission with unrelated "ethical" concerns. but, like -- if food justice isn't for the people making food, who the fuck is it for?

these are all really good and important things to be aware of and I recommend gathering that info for any new meds. i don't say this to like, blame people who were not given this info by their doctors and who took meds without being given this information, but rather to give people resources for being more in control of their own medical treatment going forward 💜

CYP450 is a family of enzymes in humans. enzymes are chemicals that speed up chemical reactions; in this case, in our bodies, CYP450 enzymes process the vast majority of currently available medications. because of that, they're responsible for most drug interactions.

different substances - including medications, supplements, and even foods - can affect the CYP enzymes in different ways.

a CYP inhibitor blocks the CYP enzymes from working to process the medication. that means you can end up with more of the medication in your body than you expect. that can cause mild, moderate, or severe side effects. good examples of CYP inhibitors are St. John's wort, grapefruit, and isoniazid (a tuberculosis medication).

a CYP inducer encourages the CYP enzymes to work faster. that means you can end up with less of the medication in your body than you expect. that medication may not work as well. this can be especially dangerous in cases where, for example, you're suppressing a dangerous effect (like autoimmunity or transplant rejection). some examples of CYP inducers are insulin, tobacco, prednisone, and in some cases, St. John's wort again.

a CYP substrate is just a substance/medication that is affected by an inhibitor or inducer. birth control is a very common substrate, and its effectiveness is affected by many medications.

each substrate is related to a different family of CYP enzymes, like CYP3A4 or CYP2D6. each one responds to different inhibitors and inducers.

you can see why they often don't tell patients this stuff: It is complicated. this is pharmacokinetics! it's difficult stuff. but i really, really believe it's important. knowing how your medications affect each other can save your life. doctors and pharmacists often do not check medication interactions. sometimes it really is up to us to understand what we're putting in our bodies.

at the very least, i urge you to check drug interactions with the drugs.com interaction checker. this checker automates some of the work of cross-referencing CYP relationships. if you have an account, you can save your drug list and cross-check all of your meds at the same time. keep in mind that not all "severe" interactions will necessarily apply to you; i recommend reading the "for professionals" version of the warning to make informed decisions about whether or not you want to be concerned. (this is also something you can discuss with a good doctor if you have the good fortune to have one.)

but, if you have the capacity, at a certain number of medications (i am taking 20+) it really is worth getting to know how they interact with CYP enzymes, what effects you might need to be watching out for (more intense effects from a higher concentration of medication? less intense effects as the medication can't attain high enough concentrations to work as it normally does?), and what meds might be the culprits of new problems as you add more medications.

to cross-check CYP relationships directly, i recommend the flockhart table. search for a medication (ctrl+f helps) and you can see all its documented CYP relationships. (they also have a mobile friendly version, but i find it slightly harder to interpret.)

here's how i do it.

start with a medication or substance. let's say i'm about to start celecoxib (Celebrex), a non-steroidal anti-inflammatory drug (NSAID). on the flockhart table, it's listed as an inhibitor of CYP2D6. (ctrl+f is helpful here.)

think through what the words mean. it's an inhibitor, so it makes the enzymes not work as well. it might increase blood levels of medications that are processed by CYP2D6.

what medications are processed with that enzyme? the flockhart table lists them if you click on the name of the medication you're curious about. CYP2D6 substrates include amitriptyline (Elavil), aripiprazole (Abilify), atomoxetine (Strattera), duloxetine (Cymbalta), oxycodone (Oxycontin), and propranolol, among others.

what effects do i need to be watching for based on the affected medications? for an inhibitor, we're looking for stronger effects; for an inducer, we're looking for weaker effects. let's say i take oxycodone daily. i want to keep an eye on the way i feel when i take oxycodone. am i feeling "higher" than usual? am i feeling dazed or dizzy or numb? or let's say i take propranolol. am i feeling dizzier or more lightheaded? am i having nightmares that i wasn't before?

here's another example. what if i want to check for a substance that might not be listed on the flockhart table? grapefruit is a good example.

wikipedia is actually a great source for this (though in some cases i recommend just searching "[substance] CYP" and seeing what pops up).

head to the list of CYP450 modulators on wikipedia. ctrl+f finds three instances of grapefruit: naringenin (a CYP1A1 inhibitor), generic 'flavonoids' (inhibiting CYP2A6), and bergamottin (a powerful CYP3A4 inhibitor).

think through what the words mean. any substrate medications processed by 1A1, 2A6, or 3A4 enzymes might be dangerously increased in my bloodstream if i consume grapefruit (or anything containing those substances; earl grey tea actually contains bergamottin, too!)

what medications are processed with those enzymes? this i can check on the flockhart table, or i can stay on wikipedia. atorvastatin - a cholesterol medication - is a substrate of 3A4. so is diazepam (Valium). valproic acid, an anti-seizure medication, is a substrate of 2A6. i'm having more trouble finding substrates of 1A1. it's not listed on the flockhart table. there is a paper published that mentions theophylline (an asthma medication) and difloxacine (a fluoroquinolone antibiotic).

what effects do i need to be watching for based on the affected medications? at a glance here, i'd be worried about having too much valium or valproic acid in my system (if i took those meds) - those could have pretty serious effects on my central nervous system. likewise, having too much of that fluoroquinolone antibiotic (if i took it - and i wouldn't, because if you have hEDS you should not take fluoroquinolones unless it's a matter of life or death!) could increase my risk for serious musculoskeletal side effects like tendon rupture. it could also disrupt my bacterial microbiome.

the physician who created the flockhart table, the late dr. david flockhart, was an exemplary physician who truly, truly cared about patients - a rare treasure. everyone's CYP-related genes are different, and it affects the way we respond to medication. we know that, just as we know that CYP relationships can cause serious and harmful drug interactions. but we don't put it into clinical practice. dr. flockhart wanted to change that, and he did pave the way towards that future. we're not there yet. but i do recommend his table.

i hate that this is not something that is widely taught and widely understood. i hate that we have this knowledge about how people metabolize drugs and how drugs work with each other and we often just do not talk about it at all. i hate that i was not instructed on the risks of taking clonazepam (a benzodiazepine, in the same class as Valium) and hydrocodone (Vicodin, an opioid) simultaneously. i experienced central nervous system depression - difficulty breathing, dizziness, confusion, fatigue - multiple times as a teenager before i figured out that i shouldn't take them close together. needless to say, mixing those two drug classes can be extremely dangerous. i got lucky and just felt awful. but at certain doses or under certain circumstances, taking those two simultaneously could kill someone. Does kill people, in fact!

a responsible doctor - one of my favorite doctors! - prescribed me those medications. he just wasn't thinking. it happens all the time.

we should not have to be doing all this work. but often doctors and pharmacists simply do not think about it. and the literature they hand out with medications, while helpful, is not going to cover all possible interactions, especially for polypharmacy patients or people on unusual medications.

likewise, you should know what medications interact with your conditions - like i mentioned fluoroquinolones and hEDS earlier. or how morphine tends to activate mast cells. that's something i can't cover here, though.

Anyway I wrote a whole comic about Cyborg Franky.