hey! now that i'm on desktop, i wanted to add information about something i think should honestly be required to explain to "polypharmacy patients" (anyone who's taking multiple medications): cytochrome p450, or CYP450 for short.
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.
i know this is a lot, and i know not everyone has had the opportunity to acquire medical literacy skills so they can interpret all of this information. my inbox is always open to medical questions (i am not a doctor + i do not know your medical history but i can provide explanations and sources and explain jargon) if you are trying to figure something out and just can't. i hope that this explanation helps someone to better understand what is going on in their body, or to make informed decisions about starting or stopping a medication.
