Speaker 1: My name is Samantha.
Speaker 2: I am forty two, and I've never really paid much
Speaker 2: attention to allergies. I am allergic to mosquitoes, but my
Speaker 2: allergy has lessened in severity as I've gotten older, and
Speaker 2: I really don't even take many precautions anymore.
Speaker 1: And I have an acquired allergy to penicillin that I've
Speaker 1: had since I was a child.
Speaker 2: I moved to Florida five years ago and had my
Speaker 2: first interaction with a fire ant. I was leaving work
Speaker 2: and one fell down my shirt and stung my chest.
Speaker 2: It hurt and was itchy, but I didn't give it
Speaker 2: a second thought, and it really was just a funny
Speaker 2: story to tell my coworkers. I don't even think I
Speaker 2: had a welt to the next day. About two months ago,
Speaker 2: I was mowing my lawn in flip flops, and I
Speaker 2: know you're not supposed to do that, but it is
Speaker 2: Florida and it's August, and I really don't like wearing
Speaker 2: shoes and socks. I felt something itchy on my foot.
Speaker 2: It didn't hurt, and when I looked down, I only
Speaker 2: saw grass. So I brushed my foot off and just
Speaker 2: went about my business that evening. The top of my
Speaker 2: foot started to turn red and swell.
Speaker 1: It was itchy.
Speaker 2: It just looked like maybe a bug bite or I'd
Speaker 2: brushed up against some plant that I shouldn't have. The
Speaker 2: next day, though, I had two little white pustules form
Speaker 2: and the red area had doubled in size.
Speaker 1: I still wasn't really worried.
Speaker 2: But by the afternoon my foot was much more swollen
Speaker 2: and still very itchy, and several more white pustules had formed.
Speaker 2: I went to a clinic and they gave me a
Speaker 2: ten day round of antibiotics and told me to go
Speaker 2: to the er if it got worse. By the time
Speaker 2: I got home that evening, part of my foot had
Speaker 2: kind of a yellowish tint, and I wasn't sure if
Speaker 2: that was from the bite or whatever I had interacted with,
Speaker 2: or because I had been driving, or because I had
Speaker 2: been standing that day, so I just went back to
Speaker 2: the er to be sure.
Speaker 1: There they said it looked like ampstings.
Speaker 2: And a few days later I was out mowing my
Speaker 2: lawn again, yes still in flip flops.
Speaker 1: I had not yet learned my lesson.
Speaker 2: And I mowed over a fire ant hill that was
Speaker 2: hidden in the grass, and then I stepped on it.
Speaker 2: I immediately felt pain and itchy. When I looked down,
Speaker 2: my foot was covered with hundreds of ants all over
Speaker 2: my left.
Speaker 1: Foot and ankle.
Speaker 2: They were on my right foot, they were all over
Speaker 2: my mower. When I went to brush them off, they
Speaker 2: got on my hands and stung my hands. I was
Speaker 2: able to get them off I moved away. The pain
Speaker 2: subsided really quickly, but I was definitely feeling the itch.
Speaker 2: After I regained my composure, I realized I was fine.
Speaker 2: I finished mowing and we'd whacked my fence line. When
Speaker 2: I went inside, I put ice on my feet and
Speaker 2: sat down for a few minutes. By now, it had
Speaker 2: been about twenty minutes since I had stepped on the
Speaker 2: ant hell, and I noticed that I was itching on
Speaker 2: my braw and my waistline. But I figured, you know,
Speaker 2: I just saw a whole bunch of insects, and people
Speaker 2: get itchy after they see insect So I went to
Speaker 2: take a cold bath, and when I got undressed, I
Speaker 2: saw red patches all over my skin, chest, trunk, down
Speaker 2: my arms, down my legs, front and back, and I
Speaker 2: was like, oh, a rash. Because I've never had hives
Speaker 2: that I remember, so I didn't realize right.
Speaker 1: Away that's what that was.
Speaker 2: I was in the bath for about fifteen minutes when
Speaker 2: I started coughing and having difficulty taking deep.
Speaker 1: Breaths, and I said, this is not normal. I need
Speaker 1: to go to the AR.
Speaker 2: So I drove back into town and it's about a
Speaker 2: thirty minute drive to get to the EAR from my house.
Speaker 2: And they took me back pretty quickly into a consult
Speaker 2: room and I was chatting with the nurse while they
Speaker 2: were starting IV. I was in good spirits and everything,
Speaker 2: and then all of a sudden, my visions started to
Speaker 2: get blurry. I texted my friend, I need you er
Speaker 2: on forty third and after that, I don't remember much,
Speaker 2: but here's what I do remember. I said, several times,
Speaker 2: my vision is blurry. I'm going to be sick. I
Speaker 2: need a bag. I'm going to throw up. The nurse said,
Speaker 2: several times, take a deep breath and try to stay calm.
Speaker 2: I told her that my hearing was fuzzy. It sounded
Speaker 2: like I was underwater. I said, please help, I'm going
Speaker 2: to be sick. And I remember an oxygen canula going
Speaker 2: on my nose. I remember the nurses trying to wheel
Speaker 2: me out in the chair. That I was in but
Speaker 2: hitting a door or a wall several times. They were
Speaker 2: having difficulty maneuvering in the chair. My body convulsed. I
Speaker 2: don't know what that looked like, but it felt terrifying.
Speaker 2: I heard someone say something about fifty somethings of benaderyl.
Speaker 2: I felt a sharp jab in my arm, followed by pain,
Speaker 2: and after a while I.
Speaker 1: Was able to open my eyes.
Speaker 2: I saw my friend had arrived, and I said to
Speaker 2: no one in particular, well that was fun, and no
Speaker 2: one laughed, so I realized it was maybe more serious.
Speaker 2: A doctor came in and explained that my blood pressure
Speaker 2: had dropped to eighty six over fifty four, my heart
Speaker 2: rate had dropped forty seven, and I had had a
Speaker 2: false positive to something, so they had to do a
Speaker 2: ct with contrast. After a couple hours, they discharged me
Speaker 2: with prednizone, doxycyclin, femididine, and epinephrine pens. Obviously, I don't
Speaker 2: go walking through my yard barefoot or on flip flops,
Speaker 2: and I carry my EpiPens in a cute little fanny pack.
Speaker 2: It kind of stinks, but dying is worse. That's my
Speaker 2: allergy story.
Speaker 1: Thanks.
Speaker 3: My parents found out that I was allergic to peanuts
Speaker 3: when I was eighteen months old. After rubbing bits of
Speaker 3: a peanut butter and jelly sandwich all over myself, as
Speaker 3: babies do, I broke out in hives and was rushed
Speaker 3: to the hospital where my allergy was confirmed. From that
Speaker 3: day forward, I was taught to have the utmost caution
Speaker 3: around peanuts, and I did. I've been lucky enough to
Speaker 3: only really go into anaphylactic shock twice because it's been
Speaker 3: so rare for me. I never truly knew what all
Speaker 3: the warning signs could be for an episode, only that
Speaker 3: if I got hives, I had a very short amount
Speaker 3: of time to use my EpiPen and get immediately to
Speaker 3: a hospital. And while that advice was helpful for my
Speaker 3: first run in with anaphol axis, it unfortunately wasn't enough
Speaker 3: for my second. In February twenty twenty three, I was
Speaker 3: visiting friends in San Francisco and we went out as
Speaker 3: a group for dinner for dim sum. I made sure
Speaker 3: to ask the wait staff about peanuts and inform them
Speaker 3: of my allergy while ordering, as I always do when
Speaker 3: dining out. After my friends and I confirmed in both
Speaker 3: English and Mandarin that all of the food we ordered
Speaker 3: was safe, we dug in. As soon as the meal ended,
Speaker 3: I felt a bit flushed. I went to the bathroom
Speaker 3: and I couldn't see any hives or swelling, so I
Speaker 3: attributed the flesh to digestion and a bit of anxiety
Speaker 3: and carried on. About ten into the walk back to
Speaker 3: our airbnb, I started to feel a little winded, and
Speaker 3: five minutes after that I started to feel faint. I
Speaker 3: figured that I must be having an asthma attack. Since
Speaker 3: I couldn't really explain this constellation of symptoms otherwise, I
Speaker 3: pulled one of my friends aside and asked her if
Speaker 3: we could sit together at the nearest bus station while
Speaker 3: I called an uber back to the airbnb, since I
Speaker 3: didn't think I could make the last ten minutes of
Speaker 3: the walk. As soon as we sat down, I started
Speaker 3: to throw up and I was unable to stop.
Speaker 1: At this point, I still didn't.
Speaker 3: Know what my body was reacting to, and I was
Speaker 3: starting to dip in and out of consciousness. The friend
Speaker 3: I'd pulled aside and a kind business owner from the
Speaker 3: corner store called nine one one when I was no
Speaker 3: longer verbally responsive, and it was only then that we
Speaker 3: learned from the nine one one operator that I was
Speaker 3: in the middle of an anaphylactic episode. I had an
Speaker 3: EpiPen on me, but before the operator could finished telling
Speaker 3: my friend how to use it, an ambulance arrived and
Speaker 3: gave me a double dose of epinephrine, saving my life.
Speaker 3: While we will never know with one hundred percent certainty
Speaker 3: whether my reaction was due to cross contamination or peanut
Speaker 3: butter mixed into a sauce and forgotten, what we do
Speaker 3: know is that I took every step possible to avoid
Speaker 3: exposure to peanuts, and for whatever reason, it wasn't quite
Speaker 3: enough this time. I am incredibly lucky and grateful for
Speaker 3: my friend and that business owner, as by the time
Speaker 3: I'd realized something was seriously wrong, I'd lost the motor
Speaker 3: skills to do anything about it. Since then, I've told
Speaker 3: as many people as I can about the different presentations
Speaker 3: of anaphylaxis with the hopes of saving another person's life.
Speaker 3: After twenty eight years of caution, I still almost died
Speaker 3: of anaphylaxis. So I would urge anyone else with a
Speaker 3: fatal allergy to please stay aware of the different presentations
Speaker 3: of anaphylaxis, and I would urge everyone else to learn
Speaker 3: how to use an EpiPen just in case.
Speaker 1: Oh just terrifying.
Speaker 4: Like so, there's so many different ways that allergies terrify me.
Speaker 4: And these are both just incredible stories and I'm so
Speaker 4: glad that you're both Okay.
Speaker 1: Yeah, yeah, thank you so much for sharing those stories
Speaker 1: with us and with our listeners. We really appreciate it.
Speaker 4: And wow, yeah, thank you.
Speaker 1: Hi.
Speaker 4: I'm Aaron Welsh and I'm Erin Alman Updyke.
Speaker 1: And this is this podcast will Kill You.
Speaker 4: We're bringing you a part two of our Allergies episode
Speaker 4: we Are.
Speaker 1: I am really excited for this. I gotta say, like, yeah,
Speaker 1: anyistamines and other allergy treatments I feel like have become
Speaker 1: so much a part of our daily lives or our
Speaker 1: medicine cabin.
Speaker 4: Our medicine cabinets one hundred percent.
Speaker 1: But how do they work? And also, Erin the first
Speaker 1: time I heard of allergy shots, my mind was first
Speaker 1: like do those work? How does that actually work?
Speaker 4: I this is not accurate, but I feel like I'm
Speaker 4: really curious about the history of allergy shots because they
Speaker 4: feel a little bit like homeopathy even though they're not,
Speaker 4: Like they're not but it's a little bit like that, right,
Speaker 4: It's like give the smallest little dose and then yes, so.
Speaker 1: It's yeah, treating like with like I mean, it actually
Speaker 1: does have its roots in homeopathy, which I'm not going
Speaker 1: to talk about, but that is kind of the way
Speaker 1: that it all started, was like, oh, if a lot
Speaker 1: hurts you, then a little bit, maybe you'll get used
Speaker 1: to it.
Speaker 4: Right, Yeah, but it actually works in this case, actually works.
Speaker 3: I know.
Speaker 4: Yeah, So we will talk about how it works and
Speaker 4: where it came from and all the things for all
Speaker 4: the treatments, well most of them at least for allergies. Today,
Speaker 4: that's what we're focusing on is how last week, if
Speaker 4: you haven't listened by the way to last week's episode,
Speaker 4: it's all about what are allergies? What are they even?
Speaker 4: How do they work? Where did they come from? Evolutionarily?
Speaker 4: Why are we stuck with these things? Yeah, it's a
Speaker 4: great episode. Check it out. But this week we're talking
Speaker 4: about what do we do at them? Once you have them?
Speaker 1: What do we do about them? But before we get
Speaker 1: into all of that, we've got some very important business
Speaker 1: to get into. We do.
Speaker 4: It's quarantine. Ay time, Aaron, what.
Speaker 1: Are we drinking again? This week.
Speaker 4: Well, of course we're drinking the allergy shots this week
Speaker 4: especially yep, it is.
Speaker 1: It's a shot, right, Like, what else could we have done?
Speaker 4: We could have called it oral immunotherapy. Just kidding. It
Speaker 4: is not, but that's that's what you call it when
Speaker 4: you give some an oral allergy shot.
Speaker 1: Good blood, Aaron, that's a great one.
Speaker 4: I thank you.
Speaker 1: In the allergy shot is it's a pretty simple concoction
Speaker 1: of rum, orange juice, pineapple juice, and Quantroe dill ish.
Speaker 4: Check it out. The recipe's already posted on our social
Speaker 4: media channels, so if you're not following us there, you
Speaker 4: definitely should be. Also, did you know we're on TikTok?
Speaker 1: We are?
Speaker 4: We are? We have videos there.
Speaker 1: On our website Podcast will Kill You dot com, you
Speaker 1: can find so many varied things, right. You can find
Speaker 1: the notes for each and every one of our episodes,
Speaker 1: which has the sources. In case you wanted to read more,
Speaker 1: you can find links to our bookshop dot or affiliate account,
Speaker 1: our Goodreads list, music by Bloodmobile, links to our Patreon,
Speaker 1: links to merch links to savings. In case you're like, oh,
Speaker 1: I heard a discount code for this podcast? What was
Speaker 1: that product? What was that code? Check out our website
Speaker 1: This podcast will kill You dot com. You can find
Speaker 1: all sorts of things. Transcripts. Did I mention that transcripts?
Speaker 4: Find them? We've got them. Well, then with that, should
Speaker 4: we get started?
Speaker 1: I think we should. Let's take a quick break and begin.
Speaker 4: It feels like we need to start this section off
Speaker 4: with the briefest of reviews of how an allergy works,
Speaker 4: you know, just to be thorough. So we're gonna basically
Speaker 4: do my whole episode from last week in like one paragraph.
Speaker 4: You ready for this, I'm ready. In allergies, you get
Speaker 4: exposed to an allergen, which is almost always some type
Speaker 4: of protein. It gets into your bloodstream, your immune system
Speaker 4: decides to do a wacky thing and start making these
Speaker 4: IgE antibodies in a process known as sensitization. And then
Speaker 4: the next time that you're re exposed to that allergen,
Speaker 4: these IgE antibodies, which happen to be bound to these
Speaker 4: cells called mass cells and besa fylls, they bind to
Speaker 4: the allergen, causing those cells to burst open and spew
Speaker 4: forth all of the inflammatory junk, and our immune system
Speaker 4: goes hogwild. So in mild cases of allergies. This might
Speaker 4: lead to inflammation just near the site of exposure, like itchy, runny,
Speaker 4: watery nose and sneezing when you breathe in cat dander,
Speaker 4: itchy eyes when you get dust mite gunk into your eyes,
Speaker 4: or upset stomach and vomiting if you eat a tree nut.
Speaker 4: And in the worst case scenarios, this inflammation triggers an
Speaker 4: extensive immune response that affects the whole body and can
Speaker 4: cause anaphylaxis, where we see swelling in the mouth and
Speaker 4: throat and lungs that leads to airway constriction and difficulty breathing.
Speaker 4: We see dilation of our blood vessels leading to blood
Speaker 4: pressure drops, which is sudden and dangerous, and this is
Speaker 4: an emergency, life threatening scenario. Was that a good summary
Speaker 4: of allergies in seconds?
Speaker 1: Yeah, it made me want to ask more questions that
Speaker 1: I was like erin, this is not about allergies. That
Speaker 1: was last week. You had your opportunity for the medications part, right.
Speaker 4: So that's the question we're trying to get to today
Speaker 4: is what the heck do we do about these? How
Speaker 4: do we treat them? It's probably logical to most people
Speaker 4: that the treatment is going to vary in part depending
Speaker 4: on the type of allergy and the severity across the board.
Speaker 4: The first answer that most people will get on how
Speaker 4: do I deal with my allergies is oh, avoid allergens,
Speaker 4: and A that's not always possible, and B sometimes there's
Speaker 4: not really that much data that it's helpful, like in
Speaker 4: the cases of things like dust mites, Like you can
Speaker 4: do all these things, and there's not necessarily that much
Speaker 4: data that it helps your allergies that much because they're
Speaker 4: ubiquitoused there every right, right, So once this allergic response
Speaker 4: kicks off and starts to run away like a boulder
Speaker 4: down a hill, what do we do about it? There
Speaker 4: are three main categories of treatment options that will talk
Speaker 4: in detail about, and then there are some others, and
Speaker 4: then at the end of this episode we'll talk about
Speaker 4: the really exciting, more novel treatments. But the three main
Speaker 4: treatments that we'll focus on today are anahistamines, allergy shots,
Speaker 4: and EpiPens. That's a brand name, so I should say
Speaker 4: epinephrine autoinjectable devices.
Speaker 1: Can we say EpiPen because it's such a mouse.
Speaker 4: You can say not sponsored EpiPen. Okay. We'll also give
Speaker 4: honorable mention to steroids, and I'll talk about them a
Speaker 4: little bit as well.
Speaker 1: Honorable honorable mention steroids, one of the most important classes
Speaker 1: of drugs, just gets an honorable mention for allergies.
Speaker 4: I know, I know, well, you know you gotta make
Speaker 4: choices here, erin, it's a podcast.
Speaker 1: It's true, It's true.
Speaker 4: Okay, So anna histamines, let us start there, shall we?
Speaker 4: Anna histamines are things like diphen hydromene. That's your benadryl. Again,
Speaker 4: I'm gonna say a lot of brand names this episode,
Speaker 4: which is not typical for us, but that way people
Speaker 4: know what we're actually talking about. Also things like hydroxyzine.
Speaker 4: So these are the types of anahistamines that people might
Speaker 4: think of that they're like, oh my god. If I
Speaker 4: take that, I am knocked out. They make you super sleepy.
Speaker 4: And then you have all these other anahistamines, things like setyrazine,
Speaker 4: xertech fexophenidine. I think that one's alegra loraatidine. Pretty sure
Speaker 4: that's Clarton. I could have gotten those mixed up. Who
Speaker 4: cares all of these types of medications. They're called anahistamines
Speaker 4: because they block histamine, simple as that. So histamine is
Speaker 4: one of the many, many compounds that our mast cells
Speaker 4: are spewing out when they burst open and release inflammatory
Speaker 4: juices in response to an allergen. So that is why
Speaker 4: we can use anahistamines in cases of allergic responses, because
Speaker 4: you have a ton of histamine floating around and it
Speaker 4: is very involved in the symptoms that we see. Histamine
Speaker 4: does literally so much in our body erin it is
Speaker 4: involved in regulating our gastric secretions in our guts. Histamine
Speaker 4: is involved in the regulation of our sleep wake cycle.
Speaker 4: You might only think of melatonin. It's way more complicated
Speaker 4: than that. Histaminees involved.
Speaker 1: Well, I guess that makes sense considering that some of
Speaker 1: these knock you out right.
Speaker 4: Huh yeah, I'll talk about why only some of them.
Speaker 4: But in the case of allergies, histamine is involved in
Speaker 4: things like vasodilation, so it helps to cause vasodilation of
Speaker 4: our blood vessels. It also is involved in the smooth
Speaker 4: muscle constriction that we see like bronchospasm that we see
Speaker 4: in asthma, but also in the cases of anaphylaxis and allergies,
Speaker 4: it causes increased vascular permeability, so that leakiness of our
Speaker 4: blood vessels which again in the context of an immune response,
Speaker 4: is forcing all of your blood and all of the
Speaker 4: immune reactants in your blood to the area for help. Right,
Speaker 4: that's the idea. It also is a big part of
Speaker 4: the itchiness that we feel, and so anahistamines are really
Speaker 4: useful in reducing the itchiness from allergies and other things
Speaker 4: that cause itch when it's a histamine related itch. Don't
Speaker 4: ask me how and why can.
Speaker 1: I was gonna ask again. I was like, I just
Speaker 1: asked this a few episodes ago. Why do we itch?
Speaker 3: Why?
Speaker 1: Why do we?
Speaker 4: Yeah, I don't have an answer. But histamines in the
Speaker 4: case of allergies, and so specifically the ana histamines that
Speaker 4: we use for allergies, they tend to there's a bunch
Speaker 4: of different receptors for histamine and they're numbered like one
Speaker 4: through four. So the anahistamines that we use for allergies
Speaker 4: block a receptor that histamine binds too, specifically the H
Speaker 4: one receptor. So what happens then is that we're still
Speaker 4: really leasing histamine. There's still plenty of histamine floating around
Speaker 4: when you're having an allergic reaction if you take it
Speaker 4: in a histamine, but it just can't do its job
Speaker 4: because that receptor is blocked by the medication. And so
Speaker 4: this is also like an even wider class of medications
Speaker 4: because since there are multiple types of histamine receptors, something
Speaker 4: that you might take for like acid reflux might be
Speaker 4: something like pepsid or fomodidine. That's an H two blocker,
Speaker 4: so it blocks different receptors of histamine. But sometimes if
Speaker 4: someone is having really severe allergies, they might need multiple
Speaker 4: types of histamine blockers, so they might be on a
Speaker 4: whole camaraderie. Is that a good word. I don't know
Speaker 4: a whole bunch.
Speaker 1: Of these medication, Okay, could I ask a question about it? Sure?
Speaker 1: Histamine receptors, So there are multiple histamine receptors that do
Speaker 1: different things. So that like if your body's like, hey,
Speaker 1: we need a histamine response because of this allergy or
Speaker 1: because of this thing, then come join this receptor, right,
Speaker 1: That's exactly how it codes, right.
Speaker 4: Yea pot.
Speaker 1: But the histamine molecule itself is always the same, but
Speaker 1: it's the anahistamines that are different to match those different
Speaker 1: receptors exactly.
Speaker 4: So histamine think of it as one one histamine, and
Speaker 4: this histamine binds to different receptors usually in different parts
Speaker 4: of our body. So like we have different receptors in
Speaker 4: our guts than we do in our brain, than we
Speaker 4: do in our blood vessels, And so the medicine that
Speaker 4: you take is going to block more or less specifically
Speaker 4: these different types of receptors. But like I said, there
Speaker 4: are different versions of these, right, So the things like
Speaker 4: benadryll or hydroxyzine, these are called first generation anahistamines, and
Speaker 4: these there's a few downsides to these compared to the
Speaker 4: newer ones that we use, like zertex and the aligres,
Speaker 4: et cetera. First is that they don't last as long,
Speaker 4: so you have to take them more frequently throughout the
Speaker 4: day because they're like therapeutic effect is only a few
Speaker 4: hours as opposed to like twelve or twenty four hours.
Speaker 4: But they also are able to cross the blood brain barrier,
Speaker 4: which is why benadrills and things make people so drowsy,
Speaker 4: because histamine is important in your brain. Histamine crosses the
Speaker 4: blood brain barrier, but the medication can also do that
Speaker 4: and then block those receptors and then cause sleepiness in
Speaker 4: your brain. They also tend to be a little bit
Speaker 4: less specific. So you said, like Okay, these different medications
Speaker 4: are blocking different receptors, yes, but some of them are
Speaker 4: better at that than others, and so some of these
Speaker 4: older antihistamines block a wider range of not just histamine receptors,
Speaker 4: but other things as well, which is why they tend
Speaker 4: to have more side effects across the board and interact
Speaker 4: with other medications. The newer anahistamines that we use for allergies,
Speaker 4: which are called second generation anta histamines zertex alecres not sponsored.
Speaker 4: These don't cross the blood brain barrier, and so they
Speaker 4: have less sedating side effects. They're more specific for those
Speaker 4: H one receptors, and they tend to last longer, so
Speaker 4: you can take them maybe once or twice a day.
Speaker 1: Okay, how do you know which ones to take?
Speaker 4: Oh? I don't know if I want to answer that question.
Speaker 4: I have answers to that question, but it feels like
Speaker 4: a doctor question.
Speaker 1: This is not an advice podcast.
Speaker 4: This is not I have a lot of like those
Speaker 4: caveats in this episode. In particular, we are not your doctors.
Speaker 4: This is not medical advice, but it really will depend.
Speaker 4: All of these anahistamines can be used to treat a
Speaker 4: lot of the symptoms of allergic reactions. Right, they're not
Speaker 4: treating the allergy at all, They're just treating the symptoms
Speaker 4: by blocking histamine from having an effect. But so no
Speaker 4: matter what the type of manifestation, be it allergic rhinitis, hives,
Speaker 4: food allergy where you're not having a phylaxis, of course,
Speaker 4: itching all of these symptoms that histamine is involved in,
Speaker 4: in the whole suite of allergic reactions that we talked
Speaker 4: about last week, they can help be mediated by anahistamines.
Speaker 4: Which one you choose will depend on what your allergies
Speaker 4: are and which one you respond better to, because some
Speaker 4: people respond better to some than others. What's really interesting is,
Speaker 4: especially when it comes to things like benadryl, some people
Speaker 4: have like paradoxical effects where it makes them really agitated,
Speaker 4: especially kids, which is why it's usually not recommended to
Speaker 4: give kids those because they can either be way too
Speaker 4: sedating or make them super hype or which is not fun.
Speaker 4: But all of these can potentially have a role, and
Speaker 4: sometimes people will respond really well to one for a
Speaker 4: long time and then it will just like stop working
Speaker 4: and then they have to switch to another one. Why why,
Speaker 4: we don't really know.
Speaker 1: Okay, but you can get used to a certain antihistamine.
Speaker 4: Absolutely, yeah. And is it just because all of your
Speaker 4: receptors are so saturated that then your body is like, well,
Speaker 4: I'm just not gonna like I'm gonna upregulate my receptors
Speaker 4: or what is it? We don't really know, but for
Speaker 4: some reason, at some point, that particular type of anahistamine
Speaker 4: for some people might not work as well. And if
Speaker 4: they switch to another one, which all of these are
Speaker 4: just different shapes of molecules binding to the same receptor,
Speaker 4: then it usually will work for them. But across the board,
Speaker 4: anahistamines are rarely the only thing that he's used to
Speaker 4: treat allergies. So let's keep going, shall we. Yeah, Steroids,
Speaker 4: honorable mention, have a role to play in the treatment
Speaker 4: of allergies, allergic rhinitis especially so like nasal and eye
Speaker 4: and like your face, symptoms from allergies really benefit from
Speaker 4: specifically nasal sprays that have glucocorticoids. And the reason is
Speaker 4: because steroids, kids are general anti inflammatories. They are blocking
Speaker 4: not just histamine, they're blocking your whole inflammatory response. So
Speaker 4: they're incredibly effective at calming down the inflammation in this
Speaker 4: tiny area that is your nasal passages, and they tend
Speaker 4: to be very safe and well tolerated because even though
Speaker 4: steroids might sound scary, in the case of nasal sprays,
Speaker 4: they're not super well absorbed systemically, so they're really locally
Speaker 4: treating this inflammation. So they are really awesome and like
Speaker 4: generally recommended as first line treatment for things like allergic rhinitis.
Speaker 4: Not all nasal sprays are steroid nasal sprays, okay, And
Speaker 4: so I think it can be really easy to get
Speaker 4: confused between all the different types. And there are some
Speaker 4: nasal sprays that you can really only use for like
Speaker 4: a day or two at a time before you start
Speaker 4: having pretty severe side effects from the nasal spray.
Speaker 1: Wow, Like what would those side effects be and why?
Speaker 4: It's because they're not steroids, so they're working in a
Speaker 4: way to just like constrict your blood vessels. It's for
Speaker 4: when you have like really bad like sinus infection or
Speaker 4: something and you just need to dry up your sinuses.
Speaker 4: They'll do that, but then they can cause like rebound
Speaker 4: worsening of symptoms and blah blah blah. So those are
Speaker 4: not what I'm talking about the types of medicine. I'm
Speaker 4: talking about are things like flow, Nase and nase achord.
Speaker 4: Those are the brand names in the US, but they're
Speaker 4: things like fluticozone and mometazone. Those are the steroids that
Speaker 4: are in it. There are also in a histamine nasal
Speaker 4: sprays that people can use, which again are going to
Speaker 4: do the same thing as your oral anahistamines, except locally
Speaker 4: just in your nose. Same thing with eye drops. There
Speaker 4: are anahistamine eye drops. Those tend to be less effective
Speaker 4: than steroid nasal sprays because they're more specific. They're only
Speaker 4: targeting the histamine rather than a more generalized inflammatory response.
Speaker 4: The way that steroid nasal sprays are doesn't mean there's
Speaker 4: no downside to steroid nasal sprays. The biggest side effect
Speaker 4: tends to be that it can increase the risk of
Speaker 4: nose bleeds for some people. Okay, and they usually take
Speaker 4: some time to work, so they're not like automatic. It
Speaker 4: takes several days for that steroid to build up in
Speaker 4: your nasal passages to actually then reduce that inflammation.
Speaker 1: Got it.
Speaker 4: We use steroids also topically for things like egzema or
Speaker 4: other allergic dermatitis type reactions, So topical ointments and creams
Speaker 4: that contain steroids are phenomenal. But in terms of oral medications,
Speaker 4: like we were talking about the scorched earth philosophy, Yeah, raw,
Speaker 4: that's steroids, like right, they're just wiping out your entire
Speaker 4: immune response indiscriminate exactly. So in cases of severe allergies
Speaker 4: or a severe allergic reaction, then yes, there might be
Speaker 4: like a short course of steroids, but they're really not
Speaker 4: a great option for long term treatment for oral steroids.
Speaker 4: Another honorable mention I will say it so that no
Speaker 4: one gets mad that I didn't is a medicine called
Speaker 4: Monte lucast singular is the brand name. Okay, it's controversial
Speaker 4: enough that I'm not going to go into it, but
Speaker 4: it's used mostly for asthma plus allergic rhinitis. So when
Speaker 4: you have both of those things together, this, unlike anahistamines,
Speaker 4: blocks another inflammatory bazouge called leukotrienes.
Speaker 1: But isn't that you find it in the index of
Speaker 1: a medical text book, right.
Speaker 4: Yeah, it's one of the other things that your mass
Speaker 4: cells spit out in the case of allergies, is a leucotriene,
Speaker 4: and so this medication blocks some of those, but it
Speaker 4: has a potential for more severe side effects, and we're
Speaker 4: learning more about the neuropsychiatric potential side effects of this medication,
Speaker 4: and so it is used, but not as commonly and
Speaker 4: in very more specific indications compared to these other medicines
Speaker 4: we're talking about today, okay, which include for the allergy shots. Yeah,
Speaker 4: so how does an allergy shot work? Allergy shots are
Speaker 4: something that we use really for again a wide range,
Speaker 4: but an as far as all allergies go, a narrow subset.
Speaker 4: And yet it is a wide range of different allergies,
Speaker 4: mostly inhaled allergens, things like danders mites, cockroaches, pollens, also beastings,
Speaker 4: fire ants, and other venoms. And this process most often
Speaker 4: is done subcutaneously, so it's called subcutaneous immunotherapy SCI. And
Speaker 4: essentially what happens is the person has to go usually weekly,
Speaker 4: sometimes even more frequently like a couple times a week
Speaker 4: to start, and an allergist will inject teeny tiny amounts
Speaker 4: of the thing that they're allergic to underneath their skin.
Speaker 1: It's just like iocane powder in The Princess Bride. But
Speaker 1: it works.
Speaker 4: I don't I have watched that movie, but I don't remember.
Speaker 1: Can he's building up a tolerance to iyakane powder.
Speaker 4: Oh okay, now I do remember.
Speaker 1: Yeah, so he doesn't die and he puts it in
Speaker 1: both of the drinks.
Speaker 4: Yeah yeaheah, I do remember that now, thank you. It's
Speaker 4: just like that, Aaron. That's how allergy shots it is,
Speaker 4: literally what that is. So you start out weekly or
Speaker 4: multiple times a week, and then you slowly are building
Speaker 4: up the amount of allergen that this person's being exposed to,
Speaker 4: and over time you space it out to less frequently
Speaker 4: every couple of weeks, every month, every few months, and
Speaker 4: this goes on for usually a couple of years, at
Speaker 4: least many many months, and then eventually you can stop
Speaker 4: doing the shots altogether and people don't have allergies or
Speaker 4: have significantly less of a response to allergens.
Speaker 1: Aaron, Why does that continuous exposure result in decrease sensitivity
Speaker 1: rather than increase sensitivity.
Speaker 4: It's a really good question. I think if we fully
Speaker 4: understood why this works, then we'd have a lot better
Speaker 4: treatment for all of our other allergies. And we don't.
Speaker 4: But what we do know what is happening. So what
Speaker 4: is happening is that this very minute, really really really
Speaker 4: small amount but frequent and repeated exposure. What it does
Speaker 4: is it kind of retrains our immune system and it
Speaker 4: induces a level of tolerance. So the way that I
Speaker 4: think of it is this repeated exposure over time trains
Speaker 4: our immune system to be like, hey, listen, remember in
Speaker 4: last week's episode, we talked about door number one and
Speaker 4: door number two and how allergies they're opening too much
Speaker 4: of door number two. So what this process is doing
Speaker 4: is telling our immune system listen, like, we've opened up
Speaker 4: enough of door number two. Like we've done it. It's overplayed.
Speaker 4: Chill out with that over response. And then what our
Speaker 4: immune system does is it starts to shift to the
Speaker 4: production of IgA and IgG antibodies and away from the
Speaker 4: production of IgE antibodies.
Speaker 1: And what do IgA and IgG do.
Speaker 4: Well, they don't trigger this mass cell type response, right.
Speaker 4: It means that our bodies can still see and flag
Speaker 4: these allergens because we have these other antibodies to them,
Speaker 4: but we're never going to trigger that severe immune response
Speaker 4: unless you have IgG antibodies. And so we are shifting
Speaker 4: production to where we can be like, yes, immune system
Speaker 4: recognize this, you can remember this allergen, but you don't
Speaker 4: need to freak out about it.
Speaker 1: Okay.
Speaker 4: Unsurprisingly, this can also backfire and can induce anaphylaxis because
Speaker 4: you are literally exposing somebody on purpose to something that
Speaker 4: their body has already been trained to identify and attack.
Speaker 4: So it's like Owen Grady is training velociraptors. That's like
Speaker 4: the process of have you seen Jurassic Worlds?
Speaker 3: No?
Speaker 1: I just I stopped at Jurassic Park three.
Speaker 4: Okay, well everyone else is going to know what I'm
Speaker 4: talking about. Imagine someone trying to train a velociraptor, right, Like,
Speaker 4: it might work because they're very smart, right, and so
Speaker 4: they might learn, okay, don't attack this thing. But you
Speaker 4: also could get your arm bit off. And that is
Speaker 4: why allergy shots are always done in a very highly
Speaker 4: regulated and monitored setting under direction of an allergist. And
Speaker 4: it's not something that people do like at home.
Speaker 1: Right, and you have to wait in the office and
Speaker 1: make sure that's a certain amount of time. Yeah.
Speaker 4: Now, there also are newer options to do this with
Speaker 4: having to poke somebody, and this process is called sublingual.
Speaker 4: Usually it's called sublingual immunotherapy, and that's when you are
Speaker 4: exposed to the allergen under your tongue and so it
Speaker 4: absorbs into your mucous membranes of your mouth rather than
Speaker 4: under your skin. It's approved for some allergens, a smaller
Speaker 4: subset of allergens than subcutaneous immunotherapy. And again we don't
Speaker 4: know exactly why, but is it because like absorption isn't
Speaker 4: as good whatever it is, We don't have as good
Speaker 4: of protocols for all the allergens for sublingual immunotherapy, but
Speaker 4: it is possible for some. So especially for kids, that's
Speaker 4: a great option because getting shots is scary.
Speaker 1: But you can't get shots for food allergies.
Speaker 4: Oh aarin or can you white? Oh? Everything that I
Speaker 4: just talked about. It's for the types of allergies that
Speaker 4: mostly are like allergic rhinitis or rhinoconjunctivitis or venoms toxins.
Speaker 4: It's not for food allergies. And it's not for lack
Speaker 4: of trying. There have been so many studies where people
Speaker 4: have tried to use subcutaneous immunotherapy or sublingual immunotherapy for
Speaker 4: food allergies. They haven't panned out, mostly because especially with
Speaker 4: subcutaneous people were just having really severe reactions. So like
Speaker 4: the reactions were more severe and then more dangerous and
Speaker 4: so nothing ever got approved. Asterisk because we'll talk more
Speaker 4: at the end of this episode about some newer therapies
Speaker 4: that are similar to this for food allergies.
Speaker 1: Teaser. Wow.
Speaker 4: I know, But until very very recently, like this year,
Speaker 4: really the only real advice for people with food allergies
Speaker 4: was avoid it, avoid it, avoid it, avoid it along
Speaker 4: with an EpiPen, which brings us to our third and
Speaker 4: final medication that we use to treat.
Speaker 1: Allergies, epinephrine autoinjector. There you go.
Speaker 4: I am really interested to hear the history of this.
Speaker 1: It's a good one.
Speaker 4: But what I'm going to talk about is like, what
Speaker 4: the heck is in an EpiPen or an epinephrin autoinjector. Well,
Speaker 4: it's epinephrine. That's easy, yep epinephrin. The other name for
Speaker 4: it that people might have heard of is adrenaline, and
Speaker 4: so epinephrin or adrenaline, it's literally the same thing, two
Speaker 4: different names.
Speaker 1: Why it's bizarre. I mean, it's like a little bit
Speaker 1: in the history, but mostly it was just like someone
Speaker 1: liked this and someone liked that.
Speaker 4: That's what I figured. Two different people came up with that. Again, Yeah,
Speaker 4: we picked one This is a hormone that we make
Speaker 4: in our bodies. And this hormone is our like fighter
Speaker 4: flight hormone. It's our fight or flight response hormone. So
Speaker 4: epiephyrine is the thing that makes your heart pound when
Speaker 4: you get anxious. It's the thing that makes you feel
Speaker 4: jittery when you're feeling jittery when you're anxious, or when
Speaker 4: you're nervous, or when you're super excited. Epinephrin acts on
Speaker 4: these receptors in our body across our entire body, called
Speaker 4: alpha receptors, and these receptors are present on our blood
Speaker 4: vessels and they so to constrict our blood vessels. Anaphylaxis,
Speaker 4: like we talked about last week, dilates our blood vessels,
Speaker 4: so when we give this drug, we constrict them boom logic.
Speaker 4: But epinephrin does even more than that. It also works
Speaker 4: on these receptors called beta receptors, and we have a
Speaker 4: lot of these on our heart. And when epinephrin binds
Speaker 4: to these receptors on our heart, it makes our heart
Speaker 4: beat faster, and it makes our heart beat harder, so
Speaker 4: it's pumping blood through these more narrowed vessels. It also
Speaker 4: through these beta receptors in our lungs, relaxes the muscles
Speaker 4: in our airways to reverse that broncho constriction or bronchospasm
Speaker 4: that we see. So that is why epinephrine is the medicine.
Speaker 4: It is the medicine to treat anaphylaxis. Like, point blank period,
Speaker 4: this is what you use. Okay, I kind of have
Speaker 4: a silly there's no such thing.
Speaker 1: Okay. Well, so let's say that you know that you
Speaker 1: are really really allergic to beastings and you see a bee.
Speaker 1: Presumably does that mean that you're adrenaline would shoot up?
Speaker 1: Would that make you less likely to have an anaphylactic reaction?
Speaker 4: Aaron, that's not a silly question. That is such a
Speaker 4: fun question.
Speaker 1: Or like a snake bite. You see a snake and
Speaker 1: you're like, ah, and then it bites you, and you're
Speaker 1: freaked out that the snake bit you, and then your
Speaker 1: body is like anaphyl access time, and then your body's
Speaker 1: also like but we just saw a snake.
Speaker 4: So Aaron, this is such a fun question in the
Speaker 4: context of the history, and like the toxin hypothesis from
Speaker 4: last week. Yeah, I have no idea.
Speaker 1: I have no idea either.
Speaker 4: I have absolutely no idea. I like, I don't even
Speaker 4: know how you would study that, Like if someone is
Speaker 4: anxious before they Yeah, I have no idea how you
Speaker 4: would study that because we can't even do like placebo
Speaker 4: controlled trials on epinephrine because it would be unethical.
Speaker 1: And how durable is an adrenaline spike, right versus the anaphylaxis, etcetera?
Speaker 4: Right? And is it just that in anaphylaxis do you
Speaker 4: just not have enough endogenous adrenaline? Are you just not
Speaker 4: making enough epinephrin? And that is why, right, Because here's
Speaker 4: the other thing, and this is where epiephrin gets a
Speaker 4: little bit weird. These beta receptors they also do vasodilation,
Speaker 4: which is what is happening in anaphylaxis. So if you
Speaker 4: give someone some epiephrin but not enough, like a lower
Speaker 4: dose of it, then those effects can override and be
Speaker 4: stronger than the vaso constriction effects on the alpha receptors.
Speaker 4: And so the dose is actually really important in epinephrine.
Speaker 1: Okay, So each EpiPen contains a dose specific to the
Speaker 1: person that it is prescribed for.
Speaker 4: Absolutely not aaron be personalized medicine, and we don't have that. Wait,
Speaker 4: so an epinephrin autoinjector EpiPen. I will throw out other
Speaker 4: trade names and a penn emorad fast jecked that's what
Speaker 4: one is called in German. Love that these devices are
Speaker 4: fixed dose injectors in the US, they're mostly in two doses.
Speaker 4: For kids they're point one five milligrams and for adults
Speaker 4: they're point three milligrams. That's it. Those are the two
Speaker 4: dose options, and you get prescribed them based on weight.
Speaker 4: So babies and small kids are going to get the
Speaker 4: small dose. Everyone else is going to get the big dose,
Speaker 4: which means some people might be overdosed, some people might
Speaker 4: be underdosed. But across the board, I know your face
Speaker 4: is like, that sounds horrible. Why yeah, But it's also
Speaker 4: like across the board, even though there are potential side effects,
Speaker 4: how long ago side effects last are usually not that long.
Speaker 4: And so these are the doses that are considered across
Speaker 4: the board safe. And so you give the dose that
Speaker 4: is closest to that person's weight based on their weight.
Speaker 1: Why would we not have a finer system for doing this?
Speaker 4: Oh my gosh, Arin, that is a question for pharmaceutical
Speaker 4: companies and who's making the most money off of.
Speaker 1: This, and there's already price gouging going on, like yeah,
Speaker 1: with EpiPens or epinephrin autoinjectors. Excuse me, I don't know
Speaker 1: which companies are doing the price gouging, but does happen?
Speaker 4: I don't have an answer to that. But these doses
Speaker 4: work for most people. When I say like underdose or overdose,
Speaker 4: it's not a large segment of the population. It's more
Speaker 4: likely that somebody might be underdosed, but at least you're
Speaker 4: still buying time.
Speaker 1: Okay.
Speaker 4: It's also the case that many people, regardless of whether
Speaker 4: it was the perfect like weight based dose or not,
Speaker 4: might need more than one because this epiphyrin doesn't last
Speaker 4: for very long. The effects are very rapid onset but transient,
Speaker 4: and so a lot of times they will help, but
Speaker 4: then that's not enough going to need multiple doses. People
Speaker 4: might even need an infusion of epinephrin running over a
Speaker 4: really long time period, like multiple hours, before their body
Speaker 4: is really out of the woods.
Speaker 1: Wow. Yeah.
Speaker 4: So in general, one of the benefits of these autoinjectors
Speaker 4: is that they are standardized across the board, so no
Speaker 4: matter what pen you can find, if someone needs one,
Speaker 4: you can use it right it's the same dose for everyone,
Speaker 4: so it's easy in that way. They're also designed to
Speaker 4: deliver the epinephrin directly into the muscle, and we usually
Speaker 4: use the thigh muscle because it's a nice, juicy, beefy
Speaker 4: muscle that has a ton of really good blood vessels
Speaker 4: and really good blood supply, which means that the epinephrin
Speaker 4: gets delivered in a really predictable way to the blood
Speaker 4: as opposed to intravenous, which you can have much higher
Speaker 4: side effects. Plus then you have to find somebody's vein,
Speaker 4: which in an emergency isn't easy to do, and subcutaneous administration,
Speaker 4: so just putting it into the se skin or like
Speaker 4: just under the skin rather than into the muscle. What
Speaker 4: happens is that you have so much local vasoconstriction from
Speaker 4: the medicine that you don't have as much penetration quickly
Speaker 4: into the bloodstream, so it doesn't work quite as well.
Speaker 4: Still better than nothing.
Speaker 1: And seconds matter, like, yeah, seconds absolutely matter. Yeah.
Speaker 4: These pens also are designed to work through clothing, so
Speaker 4: they can be delivered incredibly rapidly. You don't have to
Speaker 4: worry about like exposing someone's thigh. You just can get
Speaker 4: the medicine.
Speaker 1: In how do you know when to use one?
Speaker 4: That is a really good question, Aaron, and that is
Speaker 4: it is not something I can fully answer. But and
Speaker 4: there have also been studies and there's a paper that
Speaker 4: I'll link to in our sources about like pros and
Speaker 4: cons of at what point in an allergic response, like
Speaker 4: do you wait for things to get more severe or
Speaker 4: do you not? And the thing is that even when
Speaker 4: there are cases where yeah, maybe you could have weighted,
Speaker 4: the side effects of epinephrine generally are less severe than
Speaker 4: the risks of waiting. So usually across the board, the
Speaker 4: recommendation is if you have a known like especially if
Speaker 4: you've ever had anaphylaxis before, or if you have had
Speaker 4: severe enough reactions where maybe it's not anaphylaxis, but you're
Speaker 4: really at high risk of anaphylaxis, then the recommendation is
Speaker 4: once you see signs of a systemic response and not
Speaker 4: just like oh, just one hive or something like that,
Speaker 4: then you give it, because the risks of waiting often
Speaker 4: outweigh the risks of the medication itself.
Speaker 1: Okay, but again it's.
Speaker 4: Gonna be I'm not your doctor, so this is not
Speaker 4: medical advice. Also not medical advice. I feel very strongly
Speaker 4: that everybody should learn how to use one of these pens,
Speaker 4: even if you don't have allergies, because allergies are so common.
Speaker 4: So there's lots of great YouTube videos out there. Most
Speaker 4: of them are really similar, even though all the pens
Speaker 4: look different. Some look like a box, some look like
Speaker 4: a pen. Never ever, ever, ever put your finger over
Speaker 4: the top anyone. You hold it like it's a I
Speaker 4: don't know, a turkey leg, not.
Speaker 1: Like a I honestly, I can't think of anything else
Speaker 1: that's perfect, thank you. Why you hold a turkey leg.
Speaker 1: You're not going to hold it with like You're not
Speaker 1: going to hold it like end over the top of
Speaker 1: the time, and.
Speaker 4: Over the top. You can you can die that way anyways.
Speaker 4: And we'll talk more about other newer options for epinephrine administration,
Speaker 4: because also injecting your like shoving a needle into your
Speaker 4: leg or your child's leg, that's traumatic. Yea, So there
Speaker 4: are some really awesome newer options. But one of the
Speaker 4: biggest issues you mentioned cost Aaron. These pens can be
Speaker 4: incredibly expensive. I went on good RX and I looked
Speaker 4: them up, and the cheapest one I could find in
Speaker 4: the US is one hundred and forty dollars for two pens.
Speaker 4: If you don't have insurance or if your insurance doesn't cover,
Speaker 4: that's not cheap.
Speaker 1: No, it's not cheap.
Speaker 4: But an even bigger problem in terms of access is that,
Speaker 4: according to the World Allergy Organization of a survey of
Speaker 4: all of its member states, this type of epinephrine autoinjector
Speaker 4: is only available in sixty percent of the countries that
Speaker 4: they surveyed sixty percent.
Speaker 1: And then I would still imagine, like you know, we
Speaker 1: talked about, oh do you wait? Do you not wait?
Speaker 1: How do you know when to? And I wonder for
Speaker 1: how many people. Cost is a factor in them one.
Speaker 4: Hundred percent because then if you use it, and they
Speaker 4: also degrade within twelve to eighteen months, so they have
Speaker 4: to be replaced, so you need a new one. Even
Speaker 4: if you don't use it, you have to carry it
Speaker 4: with you all of the time because you have no
Speaker 4: idea when you might be exposed to something that could
Speaker 4: give you an anaphylactic reaction. I mean, it's it is.
Speaker 4: They are life saving medication and it is incredible and
Speaker 4: we need better options and more affordable options. So we'll
Speaker 4: talk about that a little later. But Aaron, first, tell
Speaker 4: me how did we come up with all of these
Speaker 4: different medications?
Speaker 1: Yeah, there's a lot of story to cover, so let's
Speaker 1: take a break and then I'll get started. If you
Speaker 1: look in my bathroom cabinet, you will find, among a
Speaker 1: million other things like cough drops and ibuprofen, about ten
Speaker 1: different types of anahistamine medications.
Speaker 4: Wow, that's a lot.
Speaker 1: It's a lot. Yeah, drowsy, non drowsy, generic name brand
Speaker 1: in a cold medicine combo. Ten is I don't really
Speaker 1: think it's an exaggeration. Maybe it's more like eight, but
Speaker 1: it's it's honestly, there's a lot. I'm ready for when
Speaker 1: someone visits during ragweed season and asks if we have
Speaker 1: any cleraton or walletin which is what we actually have?
Speaker 1: Which is the question?
Speaker 3: Brand?
Speaker 1: No, it's Walgreens, Okay. I don't know if we would
Speaker 1: go through a Costco size thing of Clareton Costco Allertech.
Speaker 4: Have gone through many many a bottle of Children's Alertech.
Speaker 1: My husband gets allergy shots every Saturday. I think he's
Speaker 1: actually down to every other Saturday because they seem to
Speaker 1: be helping. Yep. And while I don't personally own an EpiPen.
Speaker 1: I probably should, just in case I have family and
Speaker 1: friends who do. Considering the extremely high prevalence of allergies
Speaker 1: around the globe, it's not all that surprising that medicine
Speaker 1: has put together a stocked and diverse toolkit for dealing
Speaker 1: with this condition. But it is pretty amazing even considering
Speaker 1: the limitations of these treatments, because even though allergies were
Speaker 1: only described and linked to an exposure roughly one hundred
Speaker 1: and fifty years ago, even though we don't have a
Speaker 1: full grasp on why we develop allergies in the first
Speaker 1: place and how to prevent them entirely, we do have
Speaker 1: effective treatments and plenty more promising ones on the horizon.
Speaker 1: So what I want to do today is talk about
Speaker 1: the big three, as we've already discussed, to pay them
Speaker 1: homage right in order of their development. So we'll start
Speaker 1: with allergy immunotherapy aka allergy shots I know are theomulars
Speaker 1: I know, and histamines and epinephrine auto injectors aka your EpiPens. Okay,
Speaker 1: and let me just acknowledge that these treatments are not perfect, right,
Speaker 1: They don't work for everyone, they aren't the only ones
Speaker 1: out there, and there is certainly room for improvement, because
Speaker 1: allergy remains a debilitating condition for many people, even with
Speaker 1: these treatments available, or even with the threat of allergies
Speaker 1: out there. Right. But in most respects allergy treatment is
Speaker 1: a huge medical success story, and it's one that I'm
Speaker 1: excited to tell in three chapters, Chapter one, Thank You Vaccines.
Speaker 1: In last week's episode, I mentioned that English physician John
Speaker 1: Bostock was the first to describe allergy in eighteen nineteen
Speaker 1: hay fever, and that it was Charles Blackley in eighteen
Speaker 1: seventy who first linked hay fever to a specific exposure,
Speaker 1: in this case, grass pollen. Blackley's evidence was pretty compelling.
Speaker 1: He stuck grass pollen up his nose out of season
Speaker 1: to show that it still caused symptoms. He correlated pollen
Speaker 1: counts with prevalence and severity of hay fever symptoms, and
Speaker 1: his conclusions were simultaneously corroborated by a physician in the
Speaker 1: US who was inhaling ragweed to induce his symptoms. Wow,
Speaker 1: sounds really pleasant, right, It's hardcore, like for you, very hardcore.
Speaker 4: Would not subject myself to that. Sorry.
Speaker 1: Despite this, many scientists still doubted that grass pollen could
Speaker 1: cause such a response, and that it must be some
Speaker 1: undescribed microbe or good old hysteria. Fortunately, others were convinced
Speaker 1: enough to take matters into their own hands, like William Dunbar, who,
Speaker 1: as a hay fever sufferer himself, was personally invested in
Speaker 1: understanding what caused his seasonal symptoms. So Dunbar confirmed Blackley's
Speaker 1: findings by injecting undiluted grass pollen extract into himself and
Speaker 1: his colleague, who also had hay fever. It's just like
Speaker 1: a shot of undiluted, straight up grasp polowing.
Speaker 4: He was miserable.
Speaker 1: Yeah, yeah, both both he and his colleague had awful
Speaker 1: systemic reactions like I can't imagine. And instead of that
Speaker 1: experience persuading them from pursuing this area of study, they
Speaker 1: were like, more, we must keep doing this.
Speaker 4: Oh my god.
Speaker 1: And granted they didn't inject themselves with like full on
Speaker 1: pollen again. Instead, they took the diphtheria antitoxin approach, and
Speaker 1: they tried to produce pollen anti serum by injecting horses
Speaker 1: with grass pollen.
Speaker 4: Huh.
Speaker 1: They then turned the serum into powder which could be
Speaker 1: applied to the eyes and nose prophylactically during hay fever season.
Speaker 4: Did it work?
Speaker 1: Results were mixed, okay, some people got worse. They developed
Speaker 1: a sensitivity to the horse serum itself, something that had
Speaker 1: been known to happen with other serum antitoxins. Dunbar didn't
Speaker 1: give up hope, though, and he took one of these
Speaker 1: patients who had developed this sensitivity and started them on
Speaker 1: a pallen exposure journey. Over many weeks, he injected teeny
Speaker 1: tiny amounts of grass pollen extract alternating with horse serum,
Speaker 1: trying to get them dec sensitized to both, and at
Speaker 1: the end of fifteen increasing dosages, the patient had become
Speaker 1: much more tolerant of pollen. During that first hay fever season,
Speaker 1: they reported much more mild symptoms compared to previous years.
Speaker 4: Wow.
Speaker 1: Dunbar published his results in nineteen oh three. Nineteen oh
Speaker 1: three wow right, and he wasn't even necessarily the first
Speaker 1: to try out this concept. A few other small reports
Speaker 1: came out in a five or so years before, but
Speaker 1: it was Dunbar's paper that would catch the eye of
Speaker 1: one young researcher, Leonard Noon. Noon was on board with
Speaker 1: hay fever being caused by grass pollen, specifically quote, a
Speaker 1: soluble toxin found in the pollen of grasses. It is
Speaker 1: also undoubted that hay fever patients sometimes become cured of
Speaker 1: their idiosyncrasy. The most reasonable explanation of this phenomenon would
Speaker 1: seem to be that the cured patients have had the
Speaker 1: good fortune to develop an active immunity against the toxin
Speaker 1: to the action of which they have been liable for
Speaker 1: so long end quote.
Speaker 4: I love this, Aaron, and so.
Speaker 1: Using this logic, Noon rounded up some human volunteers and
Speaker 1: tested their sensitivity to pollen by dropping a little bit
Speaker 1: of pollen extract into their eye. Sounds horrible. And also
Speaker 1: I just wanted to note that the pollen had been
Speaker 1: collected by his sister, which I just love, Like, I
Speaker 1: love that detail so much.
Speaker 4: He's like, hess, go out, no, no, no, in this grat,
Speaker 4: just this subcrat. Okay that collected at all? Just like,
Speaker 4: just bring it back to me. It's cool. He is
Speaker 4: a glass tube, is fine.
Speaker 1: Yeah. And then in the winter and spring, outside of
Speaker 1: hay fever season, he proceeded to administer very precise doses
Speaker 1: of this pollen extract to his two groups. Those with
Speaker 1: and those without hay fever, and he increased the concentration
Speaker 1: of these doses slowly over the weeks. He experimented with
Speaker 1: different intervals between injections and found that longer intervals could
Speaker 1: actually make the patient become resensitized, and shorter intervals seemed
Speaker 1: to meaningfully reduce symptoms. Unfortunately, Nune was not able to
Speaker 1: see his experiment to the full conclusion, nor would he
Speaker 1: live to see his landmark research honored in the decades
Speaker 1: to come as the first allergen immunotherapy trial. None had tuberculosis,
Speaker 1: and over the course of the study he grew sicker
Speaker 1: and sicker, and he eventually had to turn his work
Speaker 1: over to his friend John Freeman to finish carrying out.
Speaker 1: Nune published what would be his last paper, Prophylactic Inoculation
Speaker 1: against hay Fever, in nineteen eleven, and he died two
Speaker 1: years later at the age of thirty five. Ah, that's tuberculosis,
Speaker 1: Yeah it is. Freeman continued this work for the next
Speaker 1: few years and showed that using this immunotherapy approach, in
Speaker 1: thirty per of participants, hay fever was effectively cured.
Speaker 4: Wow.
Speaker 1: In thirty five percent, symptoms were greatly improved in twenty
Speaker 1: four percent slightly improved, and only twelve percent had no
Speaker 1: improvements whatsoever. Wow, it's pretty impressive. Yeah, noon, and Freeman's
Speaker 1: work was truly foundational for the field of immunotherapy. Not
Speaker 1: only did it demonstrate that long term improvement was possible
Speaker 1: for at least one type of allergy, it also provided
Speaker 1: a roadmap for healthcare practitioners to try this out on
Speaker 1: their patients, and for researchers to tweak the protocol, testing
Speaker 1: it out with other allergens, developing a combo shot, improving
Speaker 1: safety standardization, and so on. And I'm not going to
Speaker 1: go into those later improvements. Instead, I wanted to focus
Speaker 1: on these early years because I want us to consider
Speaker 1: the timing. The time from description, identification of cause, and
Speaker 1: effective treatment happened lightning fast for hay fever in science years.
Speaker 1: But if we placed it in the context of what
Speaker 1: else was happening in the science world at the time,
Speaker 1: it's clear to see why, or at least partially why. Vaccines.
Speaker 1: Although the smallpox vaccine had been around since the late
Speaker 1: eighteen hundreds, no other vaccines were developed until the end
Speaker 1: of the nineteenth century. Around the eighteen seventies, and eighteen eighties,
Speaker 1: which is right when Blackley's work on hay fever came out,
Speaker 1: and with the growing number of vaccine success stories and
Speaker 1: the development of anti tooxin, everyone with a remote interest
Speaker 1: in microbiology or immunology began trying their hand at developing
Speaker 1: a vaccine and using the germ theory framework to describe
Speaker 1: what happens with an allergen exposure. Along with the concepts
Speaker 1: of immunity, immunization, susceptibility, toxin, antiitoxin, and so on, it
Speaker 1: seemed entirely reasonable that if vaccines worked for pathogens introduced
Speaker 1: a little bit to prevent someone from getting sick in
Speaker 1: the future, then maybe that could work for allergens. Voila
Speaker 1: allergy shots. Yeah, so in a sense, we have vaccines
Speaker 1: to think.
Speaker 4: That is so interesting, Arin, I really love that.
Speaker 1: I just can't believe how old it is, Like it
Speaker 1: makes sense, but it's also like I just can't believe it.
Speaker 1: It's also just like.
Speaker 4: So so so interesting immunologically that it works and that
Speaker 4: it works the way that it does, and like it
Speaker 4: just it makes me have so many more questions about
Speaker 4: our immune response and like tolerance versus resistance, you know
Speaker 4: what I mean?
Speaker 1: Oh, tolerance versus resistance is such a fascinating question.
Speaker 4: It really is, and it's like, oh.
Speaker 1: Yeah, yeah, And it doesn't work like vaccines in a
Speaker 1: way either, right, like vaccines sensitize you to see exactly.
Speaker 4: It is like the opposite of vaccines. Yeah, but also
Speaker 4: the same as vaccines, right, because it is it is
Speaker 4: shifting your immune RESCE response to be an IgG response,
Speaker 4: which is what we see with vaccines. But they a
Speaker 4: didn't know that, of course, and B like it is
Speaker 4: because you already had an abnormal Well is it abnormal?
Speaker 4: We don't know, but you had this IgE response and
Speaker 4: you're having to shift it. So it is it is
Speaker 4: tolerance rather than this like prime rebility to resist in
Speaker 4: the future. What I know, it is so weird.
Speaker 1: It's weird, and I love it.
Speaker 4: I love it. I love it.
Speaker 1: Are you ready for our next chapter? I really am
Speaker 1: okay chapter two? Thank you. Pharmacology. Just as allergy shots
Speaker 1: were a product of their time and the excitement surrounding vaccines,
Speaker 1: any histamines came out of an era that saw the
Speaker 1: birth of modern pharmacology. By the mid to late eighteen hundreds,
Speaker 1: the fields of chemistry and biochemistry had made huge technological
Speaker 1: advancements that allowed scientists to isolate and refine more and
Speaker 1: more compounds, especially those from living organisms. The goal of
Speaker 1: this work was basically to understand how stuff works, link
Speaker 1: a compound to its function. Then if a certain compound
Speaker 1: did something interesting or helpful, like quinine treating malaria, you
Speaker 1: could take steps to either isolate larger quantities of it
Speaker 1: from natural sources or try your hand at producing it Artificially,
Speaker 1: it sounds like a straightforward process, but in reality this
Speaker 1: type of work often led researchers down unexpected roads, which
Speaker 1: is exactly what happened for Henry Dale and George Barker.
Speaker 4: Okay.
Speaker 1: Dale and Barker were working at Sir Henry Welcome's research
Speaker 1: lab in England of Welcome Collection Welcome Library. When they
Speaker 1: turned their sites to ergit. Welcome became interested in the
Speaker 1: commercial potential of ergot as a medication to speed up
Speaker 1: labor during childbirth and reduce postpartum bleeding, both of which
Speaker 1: ergot had been shown to do. But no one really understood.
Speaker 4: How I love this. We talked about er way.
Speaker 1: Back in a dancing plague. Dancing plague, that's right, we
Speaker 1: should do just an ergic episode, really Okay.
Speaker 4: I mean we say, like we could make anything into
Speaker 4: an episode, so like, I don't know.
Speaker 1: I mean, this could have been three additional episodes. Let's like,
Speaker 1: let's be real. But ergo on its own is not
Speaker 1: something you really want to mess with, and so the
Speaker 1: key was to find the compound that had these desired effects,
Speaker 1: isolate it, and then turn it into a medication with
Speaker 1: fewer side effects than straight up ergo. So Dale, Barger
Speaker 1: and another researcher, laid Law, began this process of isolating
Speaker 1: various compounds from ergo and then injecting them into various animals.
Speaker 1: One compound in particular caught their eye. Beta. I'm gonna
Speaker 1: try to say this Beta Emma dazzle eel, folamine, or
Speaker 1: as we know it, histamine. Okay, so glad I don't
Speaker 1: have to say that again. It was brutal. Histamine had
Speaker 1: been isolated previously, but Dale and laid Law were the
Speaker 1: first to look into what it actually did, and what
Speaker 1: they found was pretty compelling. It caused all the things
Speaker 1: you talked about aaron phasodilation, the contraction of smooth muscles
Speaker 1: in the airways, in the uterus, in the intestines. It
Speaker 1: increased heart rate and stimulated contraction. Overall, injection with histamine
Speaker 1: induced a response in animals that looked a whole lot
Speaker 1: like anaphylactic shock, which they pointed out at the very
Speaker 1: end of their nineteen ten paper as a possible avenue
Speaker 1: for future research.
Speaker 4: Wow. Nineteen ten, nineteen ten.
Speaker 1: I know anaphylaxis, by the way, had only been described
Speaker 1: eight years prior in nineteen oh two, which is pretty
Speaker 1: early by Rochet and Portier. Dale and Laidlaw's paper went
Speaker 1: a long way towards linking histamine and allergy slash anaphylaxis,
Speaker 1: but the connection wasn't quite complete. This compound from ergo
Speaker 1: can cause this reaction, but does it have biological significance?
Speaker 3: Like?
Speaker 1: Is this something that animals regularly encounter? The answer to
Speaker 1: that would arrive in nineteen twenty seven, when Charles Best
Speaker 1: of insulin fame. He was one of the people who yep,
Speaker 1: he isolated histamine from liver and lungs, showing that this
Speaker 1: compound is produced regularly in animal tissue and that it
Speaker 1: plays a strong role in allergy and anaphylaxis.
Speaker 4: This is so fun, Eric, I can't tell you how
Speaker 4: much I love learning this stuff that I've never learned
Speaker 4: about like where we got anahistamines from.
Speaker 1: I know, I just also I love I think it's
Speaker 1: so fascinating to read about that period of science where
Speaker 1: it was just sort of like throwing a dart and
Speaker 1: being like cool, let's check out this compound. Yeah, and
Speaker 1: it does this thing. Let's look at this microbe. It's
Speaker 1: just everything. Yeah. Yeah, open questions so many. Once this
Speaker 1: link was made between animals produce histamine on the rag
Speaker 1: and it seems to be linked to allergy and anaphylaxis
Speaker 1: in some way, then the logic followed that if you
Speaker 1: could find a way to block the action of histamine,
Speaker 1: you could reduce those unpleasant and deadly effects that it caused.
Speaker 1: But how do you do that? Yeah, you look for
Speaker 1: compounds that bind to histamine receptors, blocking histamine from binding.
Speaker 4: I mean, straightforward when you say it like.
Speaker 1: That, straightforward, right, easy enough? I mean, but in a way,
Speaker 1: it was only ten years after Best isolated histamine from
Speaker 1: animal tissues that the first antihistamines emerged. So it was
Speaker 1: nineteen thirty seven is when Daniel Beauvet, who identified the
Speaker 1: first antihistamine and then was later awarded a Nobel Prize
Speaker 1: for his efforts. Nineteen thirty seven is one that happened.
Speaker 4: Wow.
Speaker 1: And they were on the market by the mid nineteen forties.
Speaker 4: Wow, I know that's so much earlier. Same today, I
Speaker 4: think of the nineteen fifties, it's like medicines didn't exist,
Speaker 4: which I know I had antibiotics.
Speaker 1: Yeah that's true. But yeah, that first antihistamy I feel
Speaker 1: like Benaedrux was nineteen forty six something like that. Wow.
Speaker 4: Yeah, that is so cool.
Speaker 1: And again, these are the first generation, right. I could
Speaker 1: tell a whole separate story about the research that followed
Speaker 1: from this first generation of antaistamines. You know, how we
Speaker 1: discovered the second generation histamines, all the different receptors, the
Speaker 1: recognition that they could help with things like motion sickness,
Speaker 1: the discovery that some antihistamines could have potentially harmful cardiac
Speaker 1: side effects, the identification of their sedative effect. I mean,
Speaker 1: there's a lot more to the history of antihistamines. I
Speaker 1: would read that book erin Well, I'll have to save
Speaker 1: that story for another day because we've still got the
Speaker 1: last of the big three allergy treatments to get into,
Speaker 1: and that is the epinephrine autoinjector SLASH the EpiPen, love
Speaker 1: it chapter three, Thank you Sheldon, Sheldon Sheldon. The EpiPen
Speaker 1: is one of the most powerful medical devices you hope
Speaker 1: you never have to use. It has saved countless lives
Speaker 1: from anaphylaxis since its initial introduction, and millions of people
Speaker 1: around the world rely on EpiPens to save their lives
Speaker 1: from severe allergic reactions. We owe the existence of this
Speaker 1: amazing device to two separate but equally crucial developments in medicine,
Speaker 1: the discovery of adrenaline slash epinephrine and the invention of
Speaker 1: the autoinjector. Let's begin with adrenaline again, placing ourselves in
Speaker 1: the late eighteen hundreds, when, alongside the fields of vaccinology
Speaker 1: and pharmacology, the study of hormones was also kicking off.
Speaker 1: Two researchers, George Oliver and Ea Shaeffer, ground up a
Speaker 1: bunch of adrenal glands from various animals, swirled them up
Speaker 1: with some alcohol and glycerine, and injected it into dogs
Speaker 1: just to see what would happen.
Speaker 4: Oh my goodness.
Speaker 1: Okay, yeah, not great. This idea didn't come out of
Speaker 1: thin air, though several other researchers had attempted something similar,
Speaker 1: but no one had thoroughly characterized a typical response. Usually
Speaker 1: it was just death, yeah, because it was like not
Speaker 1: very purified, right, hormone.
Speaker 4: Extra, lots of ways that that could kill a dog.
Speaker 1: Just yeah, yeah, yeah absolutely. Oliver and Schaeffer were the
Speaker 1: first to actually say, Okay, this is what happens. They
Speaker 1: noted that the dogs receiving the adrenal gland extract had
Speaker 1: elevated heart rate, vasodilation, increased blood pressure, and reduced respiratory rate.
Speaker 1: It's kind of a messy suite of symptoms. Yes, it's
Speaker 1: not messy.
Speaker 4: Adrenal glands are messy.
Speaker 1: Yeah, there's a lot of stuff going on there.
Speaker 4: They make a lot more than just adrenaline.
Speaker 1: Yeah, inducing this type of response, they recognized could come
Speaker 1: in handy, But first you needed to find out exactly
Speaker 1: what was triggering this response or the different parts of
Speaker 1: this response. Several researchers set to isolating the responsible compound,
Speaker 1: and in nineteen oh one, Jokichi Takamine would ultimately claim
Speaker 1: the title calling the substance adrenaline, which Park Davison Company,
Speaker 1: later owned by Pfizer, patented in nineteen oh three. What
Speaker 1: I don't know that, yeah, yeah.
Speaker 4: So that's why we call it up enprind because.
Speaker 1: A trade name. Yeah. Once people were able to synthetically
Speaker 1: produce adrenaline in nineteen oh six, it quickly became one
Speaker 1: of the most studied hormones over the first few decades
Speaker 1: of the twentieth century, as researchers sought to identify possible
Speaker 1: therapeutic targets among those asthma and hay fever. Since at
Speaker 1: least eighteen fifty nine, physicians had observed that quote asthma
Speaker 1: is immediately cured in situations of either sudden alarm or
Speaker 1: violent fleeting excitements.
Speaker 4: When you're activating the sympathetic nervous system eric.
Speaker 1: Uh huh, And so researchers figured, look, here's this thing,
Speaker 1: adrenaline that causes the same sensations as sudden alarm or
Speaker 1: violent fleeting excitements. Maybe we injected into people with asthma
Speaker 1: and hay fever and just see what happens. And in
Speaker 1: the first few years of the nineteen hundreds, that's exactly
Speaker 1: what Solomon solis Cohen, Jesse Bulowa, and David Kaplan did,
Speaker 1: finding that both oral and injected doses of adrenaline relieved
Speaker 1: symptoms of both conditions, but a major question remained, well,
Speaker 1: I mean several major quests remained, like what is adrenaline
Speaker 1: doing at a cellular level? But for the purposes of
Speaker 1: this history, the main unanswered question was what is the
Speaker 1: best way to get adrenaline into someone? As a treatment
Speaker 1: for hay fever and asthma. You really had to get
Speaker 1: adrenaline into someone as fast as possible to be effective,
Speaker 1: which meant injection, specifically intramuscular injection, over oral tablet or
Speaker 1: other kinds of injections. But how many people are lucky
Speaker 1: enough to have a syringe and vial of adrenaline on
Speaker 1: hand during an attack? And even if you are like
Speaker 1: drawing up the liquid into the needle while your throat
Speaker 1: is constricting not an ideal delivery system, especially when, as
Speaker 1: we talked about, every second counts. By the nineteen thirties,
Speaker 1: researchers had developed nebulizers, which helped to solve the problem
Speaker 1: for people with asthma, but getting adrenaline into someone going
Speaker 1: into anaphylaxis was still a huge challenge. Fortunately, a solution
Speaker 1: was on the horizon, but it wasn't initially created with
Speaker 1: adrenaline in mind. During the Cold War, a big fear
Speaker 1: was that troops would encounter nerve gas which acted rapidly
Speaker 1: to incapacitat or kill like nerve gas would be within seconds, right,
Speaker 1: and so the military was understandably very motivated to find
Speaker 1: a way to deliver an antidote as quickly as possible.
Speaker 4: Oh my gosh, Aaron.
Speaker 1: I know. Sheldon Kaplan an engineer working at Survival Technology Incorporated.
Speaker 1: What a name for?
Speaker 3: What a name?
Speaker 1: Right?
Speaker 4: Survival Technology? Does it still exist?
Speaker 1: But Sheldon had just the thing. One of his projects
Speaker 1: at the company was redesigning the astropen, which was an
Speaker 1: autoinjector that had limited usefulness since it used stainless steel
Speaker 1: to hold the medication rather than glass, which was thought
Speaker 1: to be too fragile. And I think, I think that
Speaker 1: this was developed with astronauts in mind. But again, you
Speaker 1: could only do certain medications because some medications when they
Speaker 1: come into contact with stainless steel, not a good thing.
Speaker 3: Interact.
Speaker 1: Yeah, okay, But this problem didn't stop Sheldon. He rebuilt
Speaker 1: the pen entirely using glass and developing a system to
Speaker 1: carefully calibrate the dose. Sheldon's new pen was called the
Speaker 1: combo pen, and this is what the military used to
Speaker 1: deliver antidotes to nerve gas.
Speaker 4: Wow.
Speaker 1: But Sheldon saw the great potential that this pen had
Speaker 1: outside of the military for the general population. He reworked
Speaker 1: it to contain adrenaline epinephrine, and the world's first epinephrine autoinjector,
Speaker 1: developed in nineteen seventy six, was officially approved by the
Speaker 1: FDA to treat anaphylaxis in nineteen eighty seven.
Speaker 4: Wow.
Speaker 1: I know he had the vision right. He saw this
Speaker 1: and was like, there's so much more that we can
Speaker 1: do with this. Wow. Yeah. The EpiPen would go on
Speaker 1: to become a household name and make pharmaceutical companies billions
Speaker 1: of dollars, thanks especially to price gouging. Yet again, but
Speaker 1: Sheldon Caplin never received any money for his invention, even
Speaker 1: though his name is on the patent. And I bet
Speaker 1: that most people have never heard of this incredible inventor
Speaker 1: whose work and brilliance has saved untold lives. Oh wow,
Speaker 1: So let's give it up to Sheldon.
Speaker 4: Kaplay gave it up for Sheldon, Oh my goodness.
Speaker 1: And there have been so many interesting developments and like
Speaker 1: you talked about different delivery systems like a box versus
Speaker 1: n you know, and there have been studies looking at well,
Speaker 1: if you conceal the needle, it makes people more likely
Speaker 1: to use it because it's less scary.
Speaker 4: Also, I am sure, and like I don't know enough
Speaker 4: about the history of development of other medications, but like
Speaker 4: we use similar types of delivery systems for so many medications. Now,
Speaker 4: It's not just epinephrine, right, yeah, even all of the
Speaker 4: ozempics of the world. The tide is the non brand name, right,
Speaker 4: Like all of these kinds of medications, insulin pens, like
Speaker 4: all of these things that have the ability to deliver
Speaker 4: a fixed dose amount in a way where you in
Speaker 4: a lot of cases have very minimal contact with the needle.
Speaker 4: Part of It's wow, that is so interesting, Arin.
Speaker 1: Yeah, so all from cold war nerve Gas, the genius
Speaker 1: of Sheldon Kaplan. I love it.
Speaker 4: How fun Aaron?
Speaker 1: Yeah.
Speaker 4: Also nineteen eighty seven. I don't know if that feels
Speaker 4: earlier late. I don't know, but I love to know
Speaker 4: that date.
Speaker 1: Yeah, I don't know how I feel about it. I'll
Speaker 1: search my soul.
Speaker 4: Yeah, same.
Speaker 1: Yeah. Well, well, Aarin, that was a quick tour through
Speaker 1: the histories of some allergy treatments, and I know that
Speaker 1: we've got a lot of interesting potential on the horizon.
Speaker 1: And so I'm going to turn it over to you
Speaker 1: to let us know where we might be going allergy
Speaker 1: treatments today.
Speaker 4: I'll do that right after this break. So we talked already, Aaron,
Speaker 4: because you asked, like, well, allergy shots, food allergies, what's up? Okay, Well,
Speaker 4: let me tell you there is a very new and
Speaker 4: by very new, I mean it was approved in the
Speaker 4: US in twenty twenty, oral immunotherapy OI as opposed to
Speaker 4: scit or slit for subcutaneous or sublingual. This is oral
Speaker 4: in your mouth imminotherapy for peanut allergy. It exists arin Yes, nice.
Speaker 4: Peanut allergy affects in the US one point two percent
Speaker 4: of the entire population and two and a half percent
Speaker 4: of kids. And peanut allergy specifically is associated with like
Speaker 4: a disproportionate amount of anaphylaxis cases that end up in
Speaker 4: the emergency room. So that is why peanut allergy has
Speaker 4: been the one that people have been studying to try
Speaker 4: and come up with treatment for. So this new treatment
Speaker 4: that exists, I didn't even write down the brand name
Speaker 4: because I didn't and now I forget. But it's a
Speaker 4: powder and it's made from peanuts, like it's just made
Speaker 4: from peanut protein erin, but it's used as oral immunotherapy
Speaker 4: in a very similar type of desensitization therapy. And the
Speaker 4: difference between this and just feeding a kid peanuts to
Speaker 4: try and desensitize them are a few things. One, it's
Speaker 4: been very well studied to be safe and well tolerated. Two,
Speaker 4: it is made to have a very specific and predictable
Speaker 4: level of allergen exposure, right. That is why it is
Speaker 4: approved and safer than just trying to eat peanuts to
Speaker 4: desensitize yourself. And the therapy regimen itself seems pretty complex.
Speaker 4: It is multiple exposures per day. It is daily exposure.
Speaker 4: It's not like subcutaneous immunotherapy where you just go like
Speaker 4: weekly exposures or something like that. And so it often
Speaker 4: starts in an allergist office or in your physician's office
Speaker 4: with these monitored, very well controlled exposures, and then has
Speaker 4: to continue at home where you're doing this every single day,
Speaker 4: often multiple times a day. And then every time that
Speaker 4: you increase the dose, which happens slowly over weeks to months,
Speaker 4: every time you increase that dose, you've got to go
Speaker 4: back to your allergis off to do that safely under
Speaker 4: guidance to make sure that you don't have an anaphylactic reaction.
Speaker 4: But it exists, Aaron.
Speaker 1: And Okay, So what is the success rate for this
Speaker 1: great question?
Speaker 4: Not perfect? I don't have an exact number. The biggest
Speaker 4: downside with this and another medicine that we'll talk about
Speaker 4: in a minute, is that it doesn't seem to produce
Speaker 4: as long lasting effects as allergy shots do. Okay, but
Speaker 4: it does have significantly increased tolerance for peanuts. Does it
Speaker 4: mean that somebody is going to no longer have a
Speaker 4: peanut allergy? No? Does it mean that they're going to
Speaker 4: be able to accidentally have peanuts or to have a
Speaker 4: little bit of peanuts in something they didn't know had
Speaker 4: peanuts without having a severe reaction or dying. Yes, And
Speaker 4: that is.
Speaker 1: Huge, right, And I imagine that it probably helps to
Speaker 1: then reduce a little bit of the anxiety and fear
Speaker 1: of a peanuts exposure.
Speaker 4: Exactly, aerin exactly, And along those same lines, there's another
Speaker 4: new medication that is really exciting and mere months ago
Speaker 4: February twenty twenty four was approved in the US for
Speaker 4: treatment of food allergy more broadly not es peanuts. And
Speaker 4: this is called oma lizumab. This is a monoclonal antibody.
Speaker 4: Anytime you see a medication like on TV that ends
Speaker 4: in mab, mab is monoclonal animal antibody.
Speaker 1: Wow, I just made that connection.
Speaker 4: So this is a medication that targets, wait for it,
Speaker 4: IgE antibodies. So we are using an antibody, an IgG
Speaker 4: antibody to find and target IgE annabodies in our body.
Speaker 4: What I know.
Speaker 1: That's wild.
Speaker 4: It's it's incredible, Aaron, It's so interesting.
Speaker 1: I love it.
Speaker 4: And it's so like the way that you do this
Speaker 4: is very similar to allergy shots in that people had
Speaker 4: to be getting shots multiple times. You don't do like
Speaker 4: a small dose and build up kind of a thing,
Speaker 4: but you have to have multiple doses over a pretty
Speaker 4: long time period. Most the study that I read that
Speaker 4: was the phase three trial of this drug before it
Speaker 4: got approved was like sixteen to twenty weeks, and then
Speaker 4: they were even checking like if we went for longer,
Speaker 4: would it have a better effect, et cetera. And what's
Speaker 4: incredible is that this showed in this trial where they
Speaker 4: took people who had at least two food allergies, so
Speaker 4: peanut allergy plus at least one other, and the ones
Speaker 4: that they ended up studying were egg, milk, cashew, wheat, hazelnut, walnut.
Speaker 4: That's just what happened people who happened to be in
Speaker 4: the trial. Sixty seven percent of people with multiple food allergies,
Speaker 4: including peanut, were able to tolerate by the end of
Speaker 4: the study at least one thousand milligrams of peanut protein,
Speaker 4: which is equivalent to four peanuts four peanuts. So that also,
Speaker 4: I think gives you a sense of just how little
Speaker 4: peanut it takes for many people with peanut allergy to
Speaker 4: have severe reaction, because in order to be included in
Speaker 4: the trial, they would have reacted to less than one
Speaker 4: hundred milligrams of peanut protein.
Speaker 1: That's wow, right, Yeah, So.
Speaker 4: By the end of the study, sixty seven percent of
Speaker 4: people were able to tolerate at least four peanuts worth
Speaker 4: of peanut protein. Forty four percent of participants tolerated up
Speaker 4: to twenty five peanuts by the end of this trial.
Speaker 1: That's awesome, it's incredible.
Speaker 4: And they saw similar results for cashew, egg milk, wheat,
Speaker 4: hazel nut. Some of these were statistically significant, some of
Speaker 4: them weren't. But here's the other thing I want to say.
Speaker 4: I feel like in a recent episode, we talked about
Speaker 4: the difference between like, is it significant clinically, is it
Speaker 4: significant statistically? Yeah, so sixty seven percent. Depending on who
Speaker 4: you are, that might sound like a lot like Okay,
Speaker 4: there's like a almost seventy percent chance that if I
Speaker 4: have food allergies, if I can get access to this medication,
Speaker 4: I might not be as allergic as I am now.
Speaker 4: But that means there's also like a thirty three percent
Speaker 4: chance that I wouldn't write. But if you break down
Speaker 4: that thirty three percent, there was like a portion of
Speaker 4: those people who did respond to the medication, as in
Speaker 4: before they maybe would respond to like one milligram or
Speaker 4: like a couple of milligrams of peanut protein, and by
Speaker 4: the end they didn't react until they hit maybe three
Speaker 4: hundred milligrams of peanut protein. So it wasn't statistically significant
Speaker 4: for the purposes of the study. But that might be
Speaker 4: the difference between I take one bite of a cookie
Speaker 4: and I realize I'm starting to have a mild reaction
Speaker 4: and I can stop, versus I take one bite of
Speaker 4: a cookie and all of a sudden I'm going into anaphylaxis,
Speaker 4: so clinically that is still significant. There was about fourteen
Speaker 4: percent of people in the study who were true failures,
Speaker 4: as in they did not sorry, they weren't failures, but
Speaker 4: they did not have any improvement in their response to this.
Speaker 1: Medication, which is interesting in and of itself, like why, yes,
Speaker 1: why are some people Why does the treatment work for
Speaker 1: some people but not others exactly?
Speaker 4: And so we don't know the answer to that because
Speaker 4: it does not work for everyone, but it works for
Speaker 4: a pretty good proportion of people. So this was just
Speaker 4: approved and again, like you mentioned Aarin, the potential that
Speaker 4: this has to improve the lives of people even though
Speaker 4: it does not mean that they're not having an allergy
Speaker 4: at all. And we still don't know because this is
Speaker 4: so new and these trials weren't that long. How long
Speaker 4: is this tolerance going to last? We don't know. Are
Speaker 4: you going to have to get this medication again? If so,
Speaker 4: is it going to work as well? There's still a
Speaker 4: lot of unanswered questions, but this medication has been shown
Speaker 4: to be safe and to be effective in increasing tolerance
Speaker 4: to so many of these food allergens, including these multiple
Speaker 4: food allergens, and that has just such a huge potential
Speaker 4: for impact on not only alleviating anaphal access saving lives,
Speaker 4: but also on reducing that anxiety. And that's something that's
Speaker 4: not like, maybe we didn't even emphasize it quite enough
Speaker 4: in last week's episode, just how severe that amount of
Speaker 4: stress can be to never know when you are going
Speaker 4: to be exposed and how severe your reaction might be.
Speaker 4: Who's going to believe you at a restaurant and who's
Speaker 4: not right?
Speaker 1: The fact that there are people who are like I
Speaker 1: don't believe in allergies. I mean, it's like not surprising
Speaker 1: given just the current state of everything in the world.
Speaker 4: But what I know, I know it's not just food
Speaker 4: allergies too. Like we talked a little bit last episode
Speaker 4: about allergic rhinitis, how it can contribute to things like
Speaker 4: difficulties in schools, anxieties. All these allergies have been shown
Speaker 4: to have significant effects on people and their families, especially
Speaker 4: for families with kids with food and other allergies. It
Speaker 4: can lead to social isolation. Like it's a These are
Speaker 4: big deals, and so the fact that we have treatments
Speaker 4: that can help to alleviate that is major and There's
Speaker 4: one more that I want to throw out there, and
Speaker 4: that is nasal epinephrine. Ah nice, even newer erin This
Speaker 4: medication was just approved in August of twenty twenty four
Speaker 4: by the FDA.
Speaker 1: Awesome.
Speaker 4: This is a no needle way to get epinephrine straight
Speaker 4: into your bloodstream in the case of an anaphylactic reaction.
Speaker 4: And I found it I'm good RX for only one
Speaker 4: hundred ninety nine dollars, which is pretty surprising considering it's
Speaker 4: not generic. Because it was just approved. This is a
Speaker 4: really exciting, like really really exciting medication. And I'm sure
Speaker 4: there's a really interesting history of this because I will
Speaker 4: link to a really cool paper that went into like
Speaker 4: what it took to be able to develop this because
Speaker 4: we needed not only the type of nasal sprayer that
Speaker 4: could spray out a fixed dose of a medication, so
Speaker 4: that technology had to develop. We also then had to
Speaker 4: develop a medication that could help other medicines be more
Speaker 4: well absorbed by your nasal mucosa so that we could
Speaker 4: more reliably get Remember I said, how like if it's
Speaker 4: absorbed into your skin, it's not gonna work as well
Speaker 4: as in your muscle. So we had to have another
Speaker 4: medicine to help it get into your bloodstream, and so
Speaker 4: we have that now, and so nasal sprays for so
Speaker 4: many medications, I think they're gonna just take off. And
Speaker 4: so this is one where now there is a nasal version,
Speaker 4: which means that it's going to be easier for people
Speaker 4: to use no needles, easier to give your kid because
Speaker 4: you don't have to poke them, which means kid might
Speaker 4: be less afraid of it. Like, there's just so many
Speaker 4: incredible things that are now possible because there's a nasal
Speaker 4: spray version of an EpiPen. It's called nefi. But all
Speaker 4: of these are new treatment options. What we still don't
Speaker 4: have is prevention aside from what we talked about in
Speaker 4: last week's episode, the leap trial and the eat trial,
Speaker 4: which I looked at back upstands for inquiring about tolerance.
Speaker 4: And these are big deals because we know that early
Speaker 4: exposure repeated exposure can reduce the risk of food allergies,
Speaker 4: especially peanuts, but for other types of allergies, we still
Speaker 4: just don't know. There's a lot of work being done.
Speaker 4: Does treating ezema early in life help to prevent allergies?
Speaker 4: Studies are so far pretty inconclusive, but there's a lot
Speaker 4: of people doing so much incredible research trying to understand
Speaker 4: what are those immunologic triggers and what can we do
Speaker 4: to try and prevent these allergies from starting in the
Speaker 4: first place, at the same time that we're trying to
Speaker 4: develop better treatments for people who already are living with allergies.
Speaker 4: It's an exciting time in the world of allergy research.
Speaker 1: It really is. It seems like there is going to
Speaker 1: just be more and more incredible developments and we're going
Speaker 1: to look back at this time and go, oh, wow,
Speaker 1: we didn't have like we have so much right now. Yeah,
Speaker 1: but we're going to have so much more in the future,
Speaker 1: I know, to bring people home. It's very exciting relief.
Speaker 4: If you want to know more, to learn so that
Speaker 4: you can be one of those future researchers. Oh my gosh,
Speaker 4: thank you. Well directly to some sources.
Speaker 1: Oh wow, I have so many for this, I don't
Speaker 1: even know where to begin, So I'll just shout out
Speaker 1: a few in particular and list the rest on the website.
Speaker 1: I'm going to shout out that one by Noon and
Speaker 1: Cantab from nineteen eleven called prophylactic inoculation against hay fever.
Speaker 1: For the antihistamine and histamine section, I'll shout out of
Speaker 1: paper by Ostrom from twenty fourteen called the History and
Speaker 1: Progression of Treatments for Allergic Rhinitis, and then for the
Speaker 1: epinephrine autoinjector. How about a paper by Arthur from twenty
Speaker 1: fifteen titled epinephrin A Short History.
Speaker 4: I have also a number of papers. A couple that
Speaker 4: I really liked that were more broad overviews was a
Speaker 4: paper from two thousand and eight from Nature Reviews Immunology
Speaker 4: called Treatment Strategies for Allergy and Asthma, and then an
Speaker 4: update from twenty twenty three, also from Nature Reviews Immunology
Speaker 4: called Allergy and Immunotherapy Past, Present, in Future. But I
Speaker 4: have a whole bunch more specifics on anahistamines, more specifics
Speaker 4: on food, allergy treatment, and epinephrine. You can find the
Speaker 4: list of the sources from this episode and all of
Speaker 4: our episodes on our website this podcast wikill you dot
Speaker 4: Com under the episodes tab.
Speaker 1: Thank you again so much to the providers of our
Speaker 1: first hand accounts and for being willing to relive those
Speaker 1: experiences through sharing your story.
Speaker 4: Yeah, thank you so much, we really appreciate it.
Speaker 1: Thank you to Bloodmobile for providing the music for this
Speaker 1: episode and all of our episodes.
Speaker 4: Thank you to Tom Briifogel and Leona Scolacchi for the
Speaker 4: audio mixing.
Speaker 1: Thank you to everyone exactly right, and.
Speaker 4: Thank you to you listeners. We hope that you enjoyed
Speaker 4: this two parter and that you learned a little bit
Speaker 4: or a lot of bit about allergies and how they
Speaker 4: work and why we treat them.
Speaker 1: I've certainly learned all the lot of it me too.
Speaker 1: And a special thank you, of course, to our lovely
Speaker 1: generous patrons. We appreciate the support that you give us
Speaker 1: so so very much.
Speaker 4: We do, we do well.
Speaker 1: Until next time, wash your hands
Speaker 4: You feel the animals