WEBVTT - Ep 162 Allergies Part 2: Shots, pills, & pens

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<v Speaker 1>My name is Samantha.

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<v Speaker 2>I am forty two, and I've never really paid much

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<v Speaker 2>attention to allergies. I am allergic to mosquitoes, but my

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<v Speaker 2>allergy has lessened in severity as I've gotten older, and

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<v Speaker 2>I really don't even take many precautions anymore.

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<v Speaker 1>And I have an acquired allergy to penicillin that I've

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<v Speaker 1>had since I was a child.

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<v Speaker 2>I moved to Florida five years ago and had my

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<v Speaker 2>first interaction with a fire ant. I was leaving work

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<v Speaker 2>and one fell down my shirt and stung my chest.

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<v Speaker 2>It hurt and was itchy, but I didn't give it

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<v Speaker 2>a second thought, and it really was just a funny

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<v Speaker 2>story to tell my coworkers. I don't even think I

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<v Speaker 2>had a welt to the next day. About two months ago,

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<v Speaker 2>I was mowing my lawn in flip flops, and I

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<v Speaker 2>know you're not supposed to do that, but it is

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<v Speaker 2>Florida and it's August, and I really don't like wearing

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<v Speaker 2>shoes and socks. I felt something itchy on my foot.

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<v Speaker 2>It didn't hurt, and when I looked down, I only

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<v Speaker 2>saw grass. So I brushed my foot off and just

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<v Speaker 2>went about my business that evening. The top of my

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<v Speaker 2>foot started to turn red and swell.

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<v Speaker 1>It was itchy.

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<v Speaker 2>It just looked like maybe a bug bite or I'd

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<v Speaker 2>brushed up against some plant that I shouldn't have. The

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<v Speaker 2>next day, though, I had two little white pustules form

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<v Speaker 2>and the red area had doubled in size.

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<v Speaker 1>I still wasn't really worried.

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<v Speaker 2>But by the afternoon my foot was much more swollen

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<v Speaker 2>and still very itchy, and several more white pustules had formed.

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<v Speaker 2>I went to a clinic and they gave me a

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<v Speaker 2>ten day round of antibiotics and told me to go

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<v Speaker 2>to the er if it got worse. By the time

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<v Speaker 2>I got home that evening, part of my foot had

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<v Speaker 2>kind of a yellowish tint, and I wasn't sure if

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<v Speaker 2>that was from the bite or whatever I had interacted with,

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<v Speaker 2>or because I had been driving, or because I had

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<v Speaker 2>been standing that day, so I just went back to

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<v Speaker 2>the er to be sure.

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<v Speaker 1>There they said it looked like ampstings.

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<v Speaker 2>And a few days later I was out mowing my

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<v Speaker 2>lawn again, yes still in flip flops.

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<v Speaker 1>I had not yet learned my lesson.

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<v Speaker 2>And I mowed over a fire ant hill that was

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<v Speaker 2>hidden in the grass, and then I stepped on it.

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<v Speaker 2>I immediately felt pain and itchy. When I looked down,

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<v Speaker 2>my foot was covered with hundreds of ants all over

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<v Speaker 2>my left.

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<v Speaker 1>Foot and ankle.

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<v Speaker 2>They were on my right foot, they were all over

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<v Speaker 2>my mower. When I went to brush them off, they

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<v Speaker 2>got on my hands and stung my hands. I was

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<v Speaker 2>able to get them off I moved away. The pain

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<v Speaker 2>subsided really quickly, but I was definitely feeling the itch.

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<v Speaker 2>After I regained my composure, I realized I was fine.

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<v Speaker 2>I finished mowing and we'd whacked my fence line. When

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<v Speaker 2>I went inside, I put ice on my feet and

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<v Speaker 2>sat down for a few minutes. By now, it had

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<v Speaker 2>been about twenty minutes since I had stepped on the

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<v Speaker 2>ant hell, and I noticed that I was itching on

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<v Speaker 2>my braw and my waistline. But I figured, you know,

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<v Speaker 2>I just saw a whole bunch of insects, and people

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<v Speaker 2>get itchy after they see insect So I went to

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<v Speaker 2>take a cold bath, and when I got undressed, I

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<v Speaker 2>saw red patches all over my skin, chest, trunk, down

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<v Speaker 2>my arms, down my legs, front and back, and I

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<v Speaker 2>was like, oh, a rash. Because I've never had hives

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<v Speaker 2>that I remember, so I didn't realize right.

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<v Speaker 1>Away that's what that was.

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<v Speaker 2>I was in the bath for about fifteen minutes when

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<v Speaker 2>I started coughing and having difficulty taking deep.

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<v Speaker 1>Breaths, and I said, this is not normal. I need

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<v Speaker 1>to go to the AR.

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<v Speaker 2>So I drove back into town and it's about a

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<v Speaker 2>thirty minute drive to get to the EAR from my house.

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<v Speaker 2>And they took me back pretty quickly into a consult

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<v Speaker 2>room and I was chatting with the nurse while they

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<v Speaker 2>were starting IV. I was in good spirits and everything,

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<v Speaker 2>and then all of a sudden, my visions started to

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<v Speaker 2>get blurry. I texted my friend, I need you er

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<v Speaker 2>on forty third and after that, I don't remember much,

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<v Speaker 2>but here's what I do remember. I said, several times,

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<v Speaker 2>my vision is blurry. I'm going to be sick. I

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<v Speaker 2>need a bag. I'm going to throw up. The nurse said,

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<v Speaker 2>several times, take a deep breath and try to stay calm.

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<v Speaker 2>I told her that my hearing was fuzzy. It sounded

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<v Speaker 2>like I was underwater. I said, please help, I'm going

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<v Speaker 2>to be sick. And I remember an oxygen canula going

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<v Speaker 2>on my nose. I remember the nurses trying to wheel

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<v Speaker 2>me out in the chair. That I was in but

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<v Speaker 2>hitting a door or a wall several times. They were

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<v Speaker 2>having difficulty maneuvering in the chair. My body convulsed. I

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<v Speaker 2>don't know what that looked like, but it felt terrifying.

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<v Speaker 2>I heard someone say something about fifty somethings of benaderyl.

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<v Speaker 2>I felt a sharp jab in my arm, followed by pain,

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<v Speaker 2>and after a while I.

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<v Speaker 1>Was able to open my eyes.

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<v Speaker 2>I saw my friend had arrived, and I said to

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<v Speaker 2>no one in particular, well that was fun, and no

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<v Speaker 2>one laughed, so I realized it was maybe more serious.

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<v Speaker 2>A doctor came in and explained that my blood pressure

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<v Speaker 2>had dropped to eighty six over fifty four, my heart

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<v Speaker 2>rate had dropped forty seven, and I had had a

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<v Speaker 2>false positive to something, so they had to do a

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<v Speaker 2>ct with contrast. After a couple hours, they discharged me

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<v Speaker 2>with prednizone, doxycyclin, femididine, and epinephrine pens. Obviously, I don't

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<v Speaker 2>go walking through my yard barefoot or on flip flops,

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<v Speaker 2>and I carry my EpiPens in a cute little fanny pack.

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<v Speaker 2>It kind of stinks, but dying is worse. That's my

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<v Speaker 2>allergy story.

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<v Speaker 1>Thanks.

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<v Speaker 3>My parents found out that I was allergic to peanuts

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<v Speaker 3>when I was eighteen months old. After rubbing bits of

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<v Speaker 3>a peanut butter and jelly sandwich all over myself, as

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<v Speaker 3>babies do, I broke out in hives and was rushed

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<v Speaker 3>to the hospital where my allergy was confirmed. From that

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<v Speaker 3>day forward, I was taught to have the utmost caution

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<v Speaker 3>around peanuts, and I did. I've been lucky enough to

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<v Speaker 3>only really go into anaphylactic shock twice because it's been

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<v Speaker 3>so rare for me. I never truly knew what all

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<v Speaker 3>the warning signs could be for an episode, only that

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<v Speaker 3>if I got hives, I had a very short amount

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<v Speaker 3>of time to use my EpiPen and get immediately to

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<v Speaker 3>a hospital. And while that advice was helpful for my

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<v Speaker 3>first run in with anaphol axis, it unfortunately wasn't enough

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<v Speaker 3>for my second. In February twenty twenty three, I was

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<v Speaker 3>visiting friends in San Francisco and we went out as

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<v Speaker 3>a group for dinner for dim sum. I made sure

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<v Speaker 3>to ask the wait staff about peanuts and inform them

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<v Speaker 3>of my allergy while ordering, as I always do when

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<v Speaker 3>dining out. After my friends and I confirmed in both

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<v Speaker 3>English and Mandarin that all of the food we ordered

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<v Speaker 3>was safe, we dug in. As soon as the meal ended,

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<v Speaker 3>I felt a bit flushed. I went to the bathroom

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<v Speaker 3>and I couldn't see any hives or swelling, so I

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<v Speaker 3>attributed the flesh to digestion and a bit of anxiety

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<v Speaker 3>and carried on. About ten into the walk back to

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<v Speaker 3>our airbnb, I started to feel a little winded, and

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<v Speaker 3>five minutes after that I started to feel faint. I

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<v Speaker 3>figured that I must be having an asthma attack. Since

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<v Speaker 3>I couldn't really explain this constellation of symptoms otherwise, I

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<v Speaker 3>pulled one of my friends aside and asked her if

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<v Speaker 3>we could sit together at the nearest bus station while

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<v Speaker 3>I called an uber back to the airbnb, since I

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<v Speaker 3>didn't think I could make the last ten minutes of

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<v Speaker 3>the walk. As soon as we sat down, I started

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<v Speaker 3>to throw up and I was unable to stop.

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<v Speaker 1>At this point, I still didn't.

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<v Speaker 3>Know what my body was reacting to, and I was

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<v Speaker 3>starting to dip in and out of consciousness. The friend

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<v Speaker 3>I'd pulled aside and a kind business owner from the

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<v Speaker 3>corner store called nine one one when I was no

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<v Speaker 3>longer verbally responsive, and it was only then that we

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<v Speaker 3>learned from the nine one one operator that I was

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<v Speaker 3>in the middle of an anaphylactic episode. I had an

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<v Speaker 3>EpiPen on me, but before the operator could finished telling

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<v Speaker 3>my friend how to use it, an ambulance arrived and

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<v Speaker 3>gave me a double dose of epinephrine, saving my life.

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<v Speaker 3>While we will never know with one hundred percent certainty

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<v Speaker 3>whether my reaction was due to cross contamination or peanut

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<v Speaker 3>butter mixed into a sauce and forgotten, what we do

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<v Speaker 3>know is that I took every step possible to avoid

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<v Speaker 3>exposure to peanuts, and for whatever reason, it wasn't quite

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<v Speaker 3>enough this time. I am incredibly lucky and grateful for

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<v Speaker 3>my friend and that business owner, as by the time

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<v Speaker 3>I'd realized something was seriously wrong, I'd lost the motor

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<v Speaker 3>skills to do anything about it. Since then, I've told

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<v Speaker 3>as many people as I can about the different presentations

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<v Speaker 3>of anaphylaxis with the hopes of saving another person's life.

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<v Speaker 3>After twenty eight years of caution, I still almost died

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<v Speaker 3>of anaphylaxis. So I would urge anyone else with a

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<v Speaker 3>fatal allergy to please stay aware of the different presentations

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<v Speaker 3>of anaphylaxis, and I would urge everyone else to learn

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<v Speaker 3>how to use an EpiPen just in case.

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<v Speaker 1>Oh just terrifying.

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<v Speaker 4>Like so, there's so many different ways that allergies terrify me.

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<v Speaker 4>And these are both just incredible stories and I'm so

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<v Speaker 4>glad that you're both Okay.

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<v Speaker 1>Yeah, yeah, thank you so much for sharing those stories

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<v Speaker 1>with us and with our listeners. We really appreciate it.

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<v Speaker 4>And wow, yeah, thank you.

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<v Speaker 1>Hi.

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<v Speaker 4>I'm Aaron Welsh and I'm Erin Alman Updyke.

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<v Speaker 1>And this is this podcast will Kill You.

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<v Speaker 4>We're bringing you a part two of our Allergies episode

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<v Speaker 4>we Are.

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<v Speaker 1>I am really excited for this. I gotta say, like, yeah,

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<v Speaker 1>anyistamines and other allergy treatments I feel like have become

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<v Speaker 1>so much a part of our daily lives or our

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<v Speaker 1>medicine cabin.

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<v Speaker 4>Our medicine cabinets one hundred percent.

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<v Speaker 1>But how do they work? And also, Erin the first

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<v Speaker 1>time I heard of allergy shots, my mind was first

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<v Speaker 1>like do those work? How does that actually work?

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<v Speaker 4>I this is not accurate, but I feel like I'm

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<v Speaker 4>really curious about the history of allergy shots because they

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<v Speaker 4>feel a little bit like homeopathy even though they're not,

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<v Speaker 4>Like they're not but it's a little bit like that, right,

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<v Speaker 4>It's like give the smallest little dose and then yes, so.

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<v Speaker 1>It's yeah, treating like with like I mean, it actually

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<v Speaker 1>does have its roots in homeopathy, which I'm not going

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<v Speaker 1>to talk about, but that is kind of the way

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<v Speaker 1>that it all started, was like, oh, if a lot

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<v Speaker 1>hurts you, then a little bit, maybe you'll get used

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<v Speaker 1>to it.

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<v Speaker 4>Right, Yeah, but it actually works in this case, actually works.

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<v Speaker 3>I know.

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<v Speaker 4>Yeah, So we will talk about how it works and

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<v Speaker 4>where it came from and all the things for all

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<v Speaker 4>the treatments, well most of them at least for allergies. Today,

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<v Speaker 4>that's what we're focusing on is how last week, if

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<v Speaker 4>you haven't listened by the way to last week's episode,

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<v Speaker 4>it's all about what are allergies? What are they even?

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<v Speaker 4>How do they work? Where did they come from? Evolutionarily?

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<v Speaker 4>Why are we stuck with these things? Yeah, it's a

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<v Speaker 4>great episode. Check it out. But this week we're talking

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<v Speaker 4>about what do we do at them? Once you have them?

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<v Speaker 1>What do we do about them? But before we get

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<v Speaker 1>into all of that, we've got some very important business

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<v Speaker 1>to get into. We do.

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<v Speaker 4>It's quarantine. Ay time, Aaron, what.

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<v Speaker 1>Are we drinking again? This week.

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<v Speaker 4>Well, of course we're drinking the allergy shots this week

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<v Speaker 4>especially yep, it is.

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<v Speaker 1>It's a shot, right, Like, what else could we have done?

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<v Speaker 4>We could have called it oral immunotherapy. Just kidding. It

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<v Speaker 4>is not, but that's that's what you call it when

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<v Speaker 4>you give some an oral allergy shot.

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<v Speaker 1>Good blood, Aaron, that's a great one.

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<v Speaker 4>I thank you.

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<v Speaker 1>In the allergy shot is it's a pretty simple concoction

0:12:41.360 --> 0:12:46.120
<v Speaker 1>of rum, orange juice, pineapple juice, and Quantroe dill ish.

0:12:46.280 --> 0:12:49.880
<v Speaker 4>Check it out. The recipe's already posted on our social

0:12:49.960 --> 0:12:51.960
<v Speaker 4>media channels, so if you're not following us there, you

0:12:52.040 --> 0:12:54.680
<v Speaker 4>definitely should be. Also, did you know we're on TikTok?

0:12:55.000 --> 0:12:55.440
<v Speaker 1>We are?

0:12:55.679 --> 0:12:57.920
<v Speaker 4>We are? We have videos there.

0:12:57.960 --> 0:13:02.320
<v Speaker 1>On our website Podcast will Kill You dot com, you

0:13:02.320 --> 0:13:06.560
<v Speaker 1>can find so many varied things, right. You can find

0:13:06.559 --> 0:13:08.520
<v Speaker 1>the notes for each and every one of our episodes,

0:13:08.520 --> 0:13:11.040
<v Speaker 1>which has the sources. In case you wanted to read more,

0:13:11.640 --> 0:13:15.000
<v Speaker 1>you can find links to our bookshop dot or affiliate account,

0:13:15.000 --> 0:13:19.360
<v Speaker 1>our Goodreads list, music by Bloodmobile, links to our Patreon,

0:13:19.480 --> 0:13:22.640
<v Speaker 1>links to merch links to savings. In case you're like, oh,

0:13:22.679 --> 0:13:25.880
<v Speaker 1>I heard a discount code for this podcast? What was

0:13:25.920 --> 0:13:29.120
<v Speaker 1>that product? What was that code? Check out our website

0:13:29.200 --> 0:13:31.280
<v Speaker 1>This podcast will kill You dot com. You can find

0:13:31.679 --> 0:13:34.960
<v Speaker 1>all sorts of things. Transcripts. Did I mention that transcripts?

0:13:34.960 --> 0:13:40.920
<v Speaker 4>Find them? We've got them. Well, then with that, should

0:13:40.960 --> 0:13:41.640
<v Speaker 4>we get started?

0:13:42.080 --> 0:13:44.800
<v Speaker 1>I think we should. Let's take a quick break and begin.

0:14:07.840 --> 0:14:09.920
<v Speaker 4>It feels like we need to start this section off

0:14:10.160 --> 0:14:13.280
<v Speaker 4>with the briefest of reviews of how an allergy works,

0:14:14.320 --> 0:14:17.920
<v Speaker 4>you know, just to be thorough. So we're gonna basically

0:14:17.960 --> 0:14:22.120
<v Speaker 4>do my whole episode from last week in like one paragraph.

0:14:22.160 --> 0:14:25.920
<v Speaker 4>You ready for this, I'm ready. In allergies, you get

0:14:25.960 --> 0:14:29.440
<v Speaker 4>exposed to an allergen, which is almost always some type

0:14:29.480 --> 0:14:33.400
<v Speaker 4>of protein. It gets into your bloodstream, your immune system

0:14:33.640 --> 0:14:37.120
<v Speaker 4>decides to do a wacky thing and start making these

0:14:37.280 --> 0:14:42.560
<v Speaker 4>IgE antibodies in a process known as sensitization. And then

0:14:42.600 --> 0:14:45.480
<v Speaker 4>the next time that you're re exposed to that allergen,

0:14:46.400 --> 0:14:50.040
<v Speaker 4>these IgE antibodies, which happen to be bound to these

0:14:50.080 --> 0:14:53.920
<v Speaker 4>cells called mass cells and besa fylls, they bind to

0:14:54.000 --> 0:14:58.400
<v Speaker 4>the allergen, causing those cells to burst open and spew

0:14:58.600 --> 0:15:02.880
<v Speaker 4>forth all of the inflammatory junk, and our immune system

0:15:02.960 --> 0:15:07.400
<v Speaker 4>goes hogwild. So in mild cases of allergies. This might

0:15:07.480 --> 0:15:11.440
<v Speaker 4>lead to inflammation just near the site of exposure, like itchy, runny,

0:15:11.520 --> 0:15:14.360
<v Speaker 4>watery nose and sneezing when you breathe in cat dander,

0:15:14.640 --> 0:15:17.600
<v Speaker 4>itchy eyes when you get dust mite gunk into your eyes,

0:15:17.960 --> 0:15:20.640
<v Speaker 4>or upset stomach and vomiting if you eat a tree nut.

0:15:21.280 --> 0:15:24.520
<v Speaker 4>And in the worst case scenarios, this inflammation triggers an

0:15:24.560 --> 0:15:28.360
<v Speaker 4>extensive immune response that affects the whole body and can

0:15:28.400 --> 0:15:32.640
<v Speaker 4>cause anaphylaxis, where we see swelling in the mouth and

0:15:32.800 --> 0:15:37.520
<v Speaker 4>throat and lungs that leads to airway constriction and difficulty breathing.

0:15:37.960 --> 0:15:40.880
<v Speaker 4>We see dilation of our blood vessels leading to blood

0:15:40.880 --> 0:15:44.880
<v Speaker 4>pressure drops, which is sudden and dangerous, and this is

0:15:44.880 --> 0:15:48.320
<v Speaker 4>an emergency, life threatening scenario. Was that a good summary

0:15:48.400 --> 0:15:50.760
<v Speaker 4>of allergies in seconds?

0:15:51.280 --> 0:15:54.000
<v Speaker 1>Yeah, it made me want to ask more questions that

0:15:54.080 --> 0:15:57.480
<v Speaker 1>I was like erin, this is not about allergies. That

0:15:57.600 --> 0:16:03.120
<v Speaker 1>was last week. You had your opportunity for the medications part, right.

0:16:03.240 --> 0:16:05.360
<v Speaker 4>So that's the question we're trying to get to today

0:16:05.480 --> 0:16:08.480
<v Speaker 4>is what the heck do we do about these? How

0:16:08.480 --> 0:16:13.160
<v Speaker 4>do we treat them? It's probably logical to most people

0:16:13.520 --> 0:16:16.680
<v Speaker 4>that the treatment is going to vary in part depending

0:16:16.720 --> 0:16:21.240
<v Speaker 4>on the type of allergy and the severity across the board.

0:16:21.480 --> 0:16:25.200
<v Speaker 4>The first answer that most people will get on how

0:16:25.200 --> 0:16:28.080
<v Speaker 4>do I deal with my allergies is oh, avoid allergens,

0:16:30.000 --> 0:16:33.440
<v Speaker 4>and A that's not always possible, and B sometimes there's

0:16:33.480 --> 0:16:35.840
<v Speaker 4>not really that much data that it's helpful, like in

0:16:35.840 --> 0:16:37.800
<v Speaker 4>the cases of things like dust mites, Like you can

0:16:37.880 --> 0:16:40.120
<v Speaker 4>do all these things, and there's not necessarily that much

0:16:40.240 --> 0:16:42.640
<v Speaker 4>data that it helps your allergies that much because they're

0:16:42.720 --> 0:16:47.440
<v Speaker 4>ubiquitoused there every right, right, So once this allergic response

0:16:47.520 --> 0:16:50.080
<v Speaker 4>kicks off and starts to run away like a boulder

0:16:50.120 --> 0:16:53.640
<v Speaker 4>down a hill, what do we do about it? There

0:16:53.680 --> 0:16:58.400
<v Speaker 4>are three main categories of treatment options that will talk

0:16:58.920 --> 0:17:01.680
<v Speaker 4>in detail about, and then there are some others, and

0:17:01.720 --> 0:17:03.640
<v Speaker 4>then at the end of this episode we'll talk about

0:17:03.680 --> 0:17:08.160
<v Speaker 4>the really exciting, more novel treatments. But the three main

0:17:08.200 --> 0:17:12.520
<v Speaker 4>treatments that we'll focus on today are anahistamines, allergy shots,

0:17:12.960 --> 0:17:16.600
<v Speaker 4>and EpiPens. That's a brand name, so I should say

0:17:16.720 --> 0:17:19.480
<v Speaker 4>epinephrine autoinjectable devices.

0:17:19.720 --> 0:17:22.600
<v Speaker 1>Can we say EpiPen because it's such a mouse.

0:17:22.480 --> 0:17:29.320
<v Speaker 4>You can say not sponsored EpiPen. Okay. We'll also give

0:17:29.359 --> 0:17:31.600
<v Speaker 4>honorable mention to steroids, and I'll talk about them a

0:17:31.600 --> 0:17:32.359
<v Speaker 4>little bit as well.

0:17:32.920 --> 0:17:37.560
<v Speaker 1>Honorable honorable mention steroids, one of the most important classes

0:17:37.600 --> 0:17:40.840
<v Speaker 1>of drugs, just gets an honorable mention for allergies.

0:17:41.040 --> 0:17:43.639
<v Speaker 4>I know, I know, well, you know you gotta make

0:17:43.680 --> 0:17:46.040
<v Speaker 4>choices here, erin, it's a podcast.

0:17:46.480 --> 0:17:48.080
<v Speaker 1>It's true, It's true.

0:17:48.359 --> 0:17:50.919
<v Speaker 4>Okay, So anna histamines, let us start there, shall we?

0:17:51.440 --> 0:17:56.240
<v Speaker 4>Anna histamines are things like diphen hydromene. That's your benadryl. Again,

0:17:56.480 --> 0:17:58.520
<v Speaker 4>I'm gonna say a lot of brand names this episode,

0:17:58.560 --> 0:18:01.200
<v Speaker 4>which is not typical for us, but that way people

0:18:01.240 --> 0:18:04.880
<v Speaker 4>know what we're actually talking about. Also things like hydroxyzine.

0:18:04.960 --> 0:18:07.440
<v Speaker 4>So these are the types of anahistamines that people might

0:18:07.480 --> 0:18:09.119
<v Speaker 4>think of that they're like, oh my god. If I

0:18:09.200 --> 0:18:12.280
<v Speaker 4>take that, I am knocked out. They make you super sleepy.

0:18:12.840 --> 0:18:16.119
<v Speaker 4>And then you have all these other anahistamines, things like setyrazine,

0:18:16.320 --> 0:18:20.800
<v Speaker 4>xertech fexophenidine. I think that one's alegra loraatidine. Pretty sure

0:18:20.800 --> 0:18:22.760
<v Speaker 4>that's Clarton. I could have gotten those mixed up. Who

0:18:22.800 --> 0:18:27.800
<v Speaker 4>cares all of these types of medications. They're called anahistamines

0:18:28.040 --> 0:18:37.399
<v Speaker 4>because they block histamine, simple as that. So histamine is

0:18:37.480 --> 0:18:42.640
<v Speaker 4>one of the many, many compounds that our mast cells

0:18:42.920 --> 0:18:47.920
<v Speaker 4>are spewing out when they burst open and release inflammatory

0:18:48.000 --> 0:18:51.960
<v Speaker 4>juices in response to an allergen. So that is why

0:18:52.000 --> 0:18:56.960
<v Speaker 4>we can use anahistamines in cases of allergic responses, because

0:18:57.200 --> 0:19:00.359
<v Speaker 4>you have a ton of histamine floating around and it

0:19:00.440 --> 0:19:04.880
<v Speaker 4>is very involved in the symptoms that we see. Histamine

0:19:05.359 --> 0:19:09.159
<v Speaker 4>does literally so much in our body erin it is

0:19:09.200 --> 0:19:14.600
<v Speaker 4>involved in regulating our gastric secretions in our guts. Histamine

0:19:14.680 --> 0:19:17.640
<v Speaker 4>is involved in the regulation of our sleep wake cycle.

0:19:17.800 --> 0:19:20.639
<v Speaker 4>You might only think of melatonin. It's way more complicated

0:19:20.720 --> 0:19:22.440
<v Speaker 4>than that. Histaminees involved.

0:19:22.640 --> 0:19:24.720
<v Speaker 1>Well, I guess that makes sense considering that some of

0:19:24.760 --> 0:19:25.960
<v Speaker 1>these knock you out right.

0:19:26.440 --> 0:19:29.760
<v Speaker 4>Huh yeah, I'll talk about why only some of them.

0:19:30.480 --> 0:19:33.760
<v Speaker 4>But in the case of allergies, histamine is involved in

0:19:33.840 --> 0:19:39.320
<v Speaker 4>things like vasodilation, so it helps to cause vasodilation of

0:19:39.359 --> 0:19:42.880
<v Speaker 4>our blood vessels. It also is involved in the smooth

0:19:42.960 --> 0:19:46.760
<v Speaker 4>muscle constriction that we see like bronchospasm that we see

0:19:46.760 --> 0:19:50.040
<v Speaker 4>in asthma, but also in the cases of anaphylaxis and allergies,

0:19:51.119 --> 0:19:55.280
<v Speaker 4>it causes increased vascular permeability, so that leakiness of our

0:19:55.320 --> 0:19:59.359
<v Speaker 4>blood vessels which again in the context of an immune response,

0:19:59.880 --> 0:20:02.760
<v Speaker 4>is forcing all of your blood and all of the

0:20:02.880 --> 0:20:07.320
<v Speaker 4>immune reactants in your blood to the area for help. Right,

0:20:07.440 --> 0:20:10.760
<v Speaker 4>that's the idea. It also is a big part of

0:20:10.840 --> 0:20:15.119
<v Speaker 4>the itchiness that we feel, and so anahistamines are really

0:20:15.240 --> 0:20:18.760
<v Speaker 4>useful in reducing the itchiness from allergies and other things

0:20:18.760 --> 0:20:21.560
<v Speaker 4>that cause itch when it's a histamine related itch. Don't

0:20:21.560 --> 0:20:23.440
<v Speaker 4>ask me how and why can.

0:20:24.160 --> 0:20:26.719
<v Speaker 1>I was gonna ask again. I was like, I just

0:20:26.800 --> 0:20:29.320
<v Speaker 1>asked this a few episodes ago. Why do we itch?

0:20:29.400 --> 0:20:29.520
<v Speaker 3>Why?

0:20:29.600 --> 0:20:30.000
<v Speaker 1>Why do we?

0:20:30.400 --> 0:20:35.040
<v Speaker 4>Yeah, I don't have an answer. But histamines in the

0:20:35.080 --> 0:20:39.639
<v Speaker 4>case of allergies, and so specifically the ana histamines that

0:20:39.680 --> 0:20:43.560
<v Speaker 4>we use for allergies, they tend to there's a bunch

0:20:43.600 --> 0:20:46.800
<v Speaker 4>of different receptors for histamine and they're numbered like one

0:20:46.800 --> 0:20:50.440
<v Speaker 4>through four. So the anahistamines that we use for allergies

0:20:50.680 --> 0:20:55.520
<v Speaker 4>block a receptor that histamine binds too, specifically the H

0:20:55.680 --> 0:20:59.680
<v Speaker 4>one receptor. So what happens then is that we're still

0:20:59.760 --> 0:21:03.040
<v Speaker 4>really leasing histamine. There's still plenty of histamine floating around

0:21:03.160 --> 0:21:05.320
<v Speaker 4>when you're having an allergic reaction if you take it

0:21:05.359 --> 0:21:08.000
<v Speaker 4>in a histamine, but it just can't do its job

0:21:08.440 --> 0:21:12.119
<v Speaker 4>because that receptor is blocked by the medication. And so

0:21:12.640 --> 0:21:15.800
<v Speaker 4>this is also like an even wider class of medications

0:21:15.840 --> 0:21:19.719
<v Speaker 4>because since there are multiple types of histamine receptors, something

0:21:19.760 --> 0:21:22.600
<v Speaker 4>that you might take for like acid reflux might be

0:21:22.680 --> 0:21:27.040
<v Speaker 4>something like pepsid or fomodidine. That's an H two blocker,

0:21:27.080 --> 0:21:31.320
<v Speaker 4>so it blocks different receptors of histamine. But sometimes if

0:21:31.400 --> 0:21:35.159
<v Speaker 4>someone is having really severe allergies, they might need multiple

0:21:35.280 --> 0:21:39.239
<v Speaker 4>types of histamine blockers, so they might be on a

0:21:39.280 --> 0:21:42.280
<v Speaker 4>whole camaraderie. Is that a good word. I don't know

0:21:42.520 --> 0:21:43.960
<v Speaker 4>a whole bunch.

0:21:43.720 --> 0:21:48.520
<v Speaker 1>Of these medication, Okay, could I ask a question about it? Sure?

0:21:48.720 --> 0:21:53.280
<v Speaker 1>Histamine receptors, So there are multiple histamine receptors that do

0:21:53.359 --> 0:21:56.160
<v Speaker 1>different things. So that like if your body's like, hey,

0:21:56.520 --> 0:22:00.520
<v Speaker 1>we need a histamine response because of this allergy or

0:22:00.560 --> 0:22:04.359
<v Speaker 1>because of this thing, then come join this receptor, right,

0:22:04.560 --> 0:22:06.280
<v Speaker 1>That's exactly how it codes, right.

0:22:06.640 --> 0:22:07.440
<v Speaker 4>Yea pot.

0:22:08.520 --> 0:22:11.879
<v Speaker 1>But the histamine molecule itself is always the same, but

0:22:11.920 --> 0:22:14.959
<v Speaker 1>it's the anahistamines that are different to match those different

0:22:15.000 --> 0:22:16.600
<v Speaker 1>receptors exactly.

0:22:16.680 --> 0:22:20.800
<v Speaker 4>So histamine think of it as one one histamine, and

0:22:20.840 --> 0:22:23.360
<v Speaker 4>this histamine binds to different receptors usually in different parts

0:22:23.359 --> 0:22:25.800
<v Speaker 4>of our body. So like we have different receptors in

0:22:25.840 --> 0:22:27.840
<v Speaker 4>our guts than we do in our brain, than we

0:22:27.880 --> 0:22:30.680
<v Speaker 4>do in our blood vessels, And so the medicine that

0:22:30.720 --> 0:22:34.520
<v Speaker 4>you take is going to block more or less specifically

0:22:34.640 --> 0:22:38.080
<v Speaker 4>these different types of receptors. But like I said, there

0:22:38.119 --> 0:22:40.919
<v Speaker 4>are different versions of these, right, So the things like

0:22:41.160 --> 0:22:47.879
<v Speaker 4>benadryll or hydroxyzine, these are called first generation anahistamines, and

0:22:48.040 --> 0:22:51.560
<v Speaker 4>these there's a few downsides to these compared to the

0:22:51.600 --> 0:22:53.960
<v Speaker 4>newer ones that we use, like zertex and the aligres,

0:22:53.960 --> 0:22:57.520
<v Speaker 4>et cetera. First is that they don't last as long,

0:22:57.680 --> 0:22:59.800
<v Speaker 4>so you have to take them more frequently throughout the

0:22:59.840 --> 0:23:03.600
<v Speaker 4>day because they're like therapeutic effect is only a few

0:23:03.640 --> 0:23:05.919
<v Speaker 4>hours as opposed to like twelve or twenty four hours.

0:23:06.640 --> 0:23:10.680
<v Speaker 4>But they also are able to cross the blood brain barrier,

0:23:11.000 --> 0:23:15.679
<v Speaker 4>which is why benadrills and things make people so drowsy,

0:23:15.760 --> 0:23:19.000
<v Speaker 4>because histamine is important in your brain. Histamine crosses the

0:23:19.000 --> 0:23:22.479
<v Speaker 4>blood brain barrier, but the medication can also do that

0:23:22.600 --> 0:23:26.800
<v Speaker 4>and then block those receptors and then cause sleepiness in

0:23:26.840 --> 0:23:30.080
<v Speaker 4>your brain. They also tend to be a little bit

0:23:30.160 --> 0:23:33.200
<v Speaker 4>less specific. So you said, like Okay, these different medications

0:23:33.240 --> 0:23:35.680
<v Speaker 4>are blocking different receptors, yes, but some of them are

0:23:35.760 --> 0:23:38.640
<v Speaker 4>better at that than others, and so some of these

0:23:38.840 --> 0:23:45.760
<v Speaker 4>older antihistamines block a wider range of not just histamine receptors,

0:23:46.080 --> 0:23:48.840
<v Speaker 4>but other things as well, which is why they tend

0:23:48.880 --> 0:23:51.639
<v Speaker 4>to have more side effects across the board and interact

0:23:51.640 --> 0:23:56.280
<v Speaker 4>with other medications. The newer anahistamines that we use for allergies,

0:23:56.280 --> 0:24:01.040
<v Speaker 4>which are called second generation anta histamines zertex alecres not sponsored.

0:24:01.840 --> 0:24:05.000
<v Speaker 4>These don't cross the blood brain barrier, and so they

0:24:05.040 --> 0:24:08.280
<v Speaker 4>have less sedating side effects. They're more specific for those

0:24:08.560 --> 0:24:12.720
<v Speaker 4>H one receptors, and they tend to last longer, so

0:24:12.760 --> 0:24:14.640
<v Speaker 4>you can take them maybe once or twice a day.

0:24:15.119 --> 0:24:18.280
<v Speaker 1>Okay, how do you know which ones to take?

0:24:20.119 --> 0:24:22.320
<v Speaker 4>Oh? I don't know if I want to answer that question.

0:24:22.359 --> 0:24:24.439
<v Speaker 4>I have answers to that question, but it feels like

0:24:24.480 --> 0:24:25.399
<v Speaker 4>a doctor question.

0:24:26.600 --> 0:24:28.359
<v Speaker 1>This is not an advice podcast.

0:24:28.520 --> 0:24:30.480
<v Speaker 4>This is not I have a lot of like those

0:24:30.520 --> 0:24:34.280
<v Speaker 4>caveats in this episode. In particular, we are not your doctors.

0:24:35.040 --> 0:24:37.520
<v Speaker 4>This is not medical advice, but it really will depend.

0:24:37.680 --> 0:24:42.040
<v Speaker 4>All of these anahistamines can be used to treat a

0:24:42.160 --> 0:24:45.119
<v Speaker 4>lot of the symptoms of allergic reactions. Right, they're not

0:24:45.160 --> 0:24:48.960
<v Speaker 4>treating the allergy at all, They're just treating the symptoms

0:24:49.080 --> 0:24:52.880
<v Speaker 4>by blocking histamine from having an effect. But so no

0:24:52.920 --> 0:24:57.560
<v Speaker 4>matter what the type of manifestation, be it allergic rhinitis, hives,

0:24:57.920 --> 0:25:01.359
<v Speaker 4>food allergy where you're not having a phylaxis, of course,

0:25:02.000 --> 0:25:06.919
<v Speaker 4>itching all of these symptoms that histamine is involved in,

0:25:06.920 --> 0:25:10.040
<v Speaker 4>in the whole suite of allergic reactions that we talked

0:25:10.080 --> 0:25:13.920
<v Speaker 4>about last week, they can help be mediated by anahistamines.

0:25:14.480 --> 0:25:17.760
<v Speaker 4>Which one you choose will depend on what your allergies

0:25:17.760 --> 0:25:20.600
<v Speaker 4>are and which one you respond better to, because some

0:25:20.640 --> 0:25:24.920
<v Speaker 4>people respond better to some than others. What's really interesting is,

0:25:25.000 --> 0:25:27.560
<v Speaker 4>especially when it comes to things like benadryl, some people

0:25:27.640 --> 0:25:31.280
<v Speaker 4>have like paradoxical effects where it makes them really agitated,

0:25:31.400 --> 0:25:35.639
<v Speaker 4>especially kids, which is why it's usually not recommended to

0:25:35.640 --> 0:25:37.959
<v Speaker 4>give kids those because they can either be way too

0:25:38.000 --> 0:25:41.440
<v Speaker 4>sedating or make them super hype or which is not fun.

0:25:43.280 --> 0:25:46.000
<v Speaker 4>But all of these can potentially have a role, and

0:25:46.040 --> 0:25:49.280
<v Speaker 4>sometimes people will respond really well to one for a

0:25:49.320 --> 0:25:51.520
<v Speaker 4>long time and then it will just like stop working

0:25:51.960 --> 0:25:54.840
<v Speaker 4>and then they have to switch to another one. Why why,

0:25:55.240 --> 0:25:55.919
<v Speaker 4>we don't really know.

0:25:56.160 --> 0:26:00.720
<v Speaker 1>Okay, but you can get used to a certain antihistamine.

0:26:00.160 --> 0:26:02.760
<v Speaker 4>Absolutely, yeah. And is it just because all of your

0:26:02.800 --> 0:26:06.120
<v Speaker 4>receptors are so saturated that then your body is like, well,

0:26:06.160 --> 0:26:09.240
<v Speaker 4>I'm just not gonna like I'm gonna upregulate my receptors

0:26:09.320 --> 0:26:11.920
<v Speaker 4>or what is it? We don't really know, but for

0:26:11.960 --> 0:26:16.600
<v Speaker 4>some reason, at some point, that particular type of anahistamine

0:26:16.600 --> 0:26:18.200
<v Speaker 4>for some people might not work as well. And if

0:26:18.200 --> 0:26:20.600
<v Speaker 4>they switch to another one, which all of these are

0:26:20.680 --> 0:26:24.080
<v Speaker 4>just different shapes of molecules binding to the same receptor,

0:26:24.600 --> 0:26:28.480
<v Speaker 4>then it usually will work for them. But across the board,

0:26:28.600 --> 0:26:33.359
<v Speaker 4>anahistamines are rarely the only thing that he's used to

0:26:33.400 --> 0:26:38.080
<v Speaker 4>treat allergies. So let's keep going, shall we. Yeah, Steroids,

0:26:38.119 --> 0:26:41.560
<v Speaker 4>honorable mention, have a role to play in the treatment

0:26:41.560 --> 0:26:46.880
<v Speaker 4>of allergies, allergic rhinitis especially so like nasal and eye

0:26:47.200 --> 0:26:53.480
<v Speaker 4>and like your face, symptoms from allergies really benefit from

0:26:53.600 --> 0:26:58.920
<v Speaker 4>specifically nasal sprays that have glucocorticoids. And the reason is

0:26:59.000 --> 0:27:04.320
<v Speaker 4>because steroids, kids are general anti inflammatories. They are blocking

0:27:04.400 --> 0:27:09.879
<v Speaker 4>not just histamine, they're blocking your whole inflammatory response. So

0:27:09.920 --> 0:27:13.600
<v Speaker 4>they're incredibly effective at calming down the inflammation in this

0:27:13.720 --> 0:27:17.800
<v Speaker 4>tiny area that is your nasal passages, and they tend

0:27:17.840 --> 0:27:21.480
<v Speaker 4>to be very safe and well tolerated because even though

0:27:21.600 --> 0:27:25.680
<v Speaker 4>steroids might sound scary, in the case of nasal sprays,

0:27:25.720 --> 0:27:30.200
<v Speaker 4>they're not super well absorbed systemically, so they're really locally

0:27:30.320 --> 0:27:34.399
<v Speaker 4>treating this inflammation. So they are really awesome and like

0:27:34.680 --> 0:27:38.480
<v Speaker 4>generally recommended as first line treatment for things like allergic rhinitis.

0:27:39.359 --> 0:27:43.639
<v Speaker 4>Not all nasal sprays are steroid nasal sprays, okay, And

0:27:43.680 --> 0:27:45.680
<v Speaker 4>so I think it can be really easy to get

0:27:45.720 --> 0:27:48.800
<v Speaker 4>confused between all the different types. And there are some

0:27:49.119 --> 0:27:52.479
<v Speaker 4>nasal sprays that you can really only use for like

0:27:52.560 --> 0:27:54.640
<v Speaker 4>a day or two at a time before you start

0:27:54.680 --> 0:27:57.520
<v Speaker 4>having pretty severe side effects from the nasal spray.

0:27:57.640 --> 0:28:00.760
<v Speaker 1>Wow, Like what would those side effects be and why?

0:28:01.560 --> 0:28:03.800
<v Speaker 4>It's because they're not steroids, so they're working in a

0:28:03.840 --> 0:28:06.159
<v Speaker 4>way to just like constrict your blood vessels. It's for

0:28:06.160 --> 0:28:08.439
<v Speaker 4>when you have like really bad like sinus infection or

0:28:08.440 --> 0:28:10.600
<v Speaker 4>something and you just need to dry up your sinuses.

0:28:10.960 --> 0:28:13.920
<v Speaker 4>They'll do that, but then they can cause like rebound

0:28:14.240 --> 0:28:18.240
<v Speaker 4>worsening of symptoms and blah blah blah. So those are

0:28:18.560 --> 0:28:21.679
<v Speaker 4>not what I'm talking about the types of medicine. I'm

0:28:21.680 --> 0:28:24.119
<v Speaker 4>talking about are things like flow, Nase and nase achord.

0:28:24.160 --> 0:28:26.440
<v Speaker 4>Those are the brand names in the US, but they're

0:28:26.480 --> 0:28:30.399
<v Speaker 4>things like fluticozone and mometazone. Those are the steroids that

0:28:30.440 --> 0:28:35.840
<v Speaker 4>are in it. There are also in a histamine nasal

0:28:35.880 --> 0:28:38.920
<v Speaker 4>sprays that people can use, which again are going to

0:28:38.960 --> 0:28:42.640
<v Speaker 4>do the same thing as your oral anahistamines, except locally

0:28:42.920 --> 0:28:46.000
<v Speaker 4>just in your nose. Same thing with eye drops. There

0:28:46.040 --> 0:28:50.200
<v Speaker 4>are anahistamine eye drops. Those tend to be less effective

0:28:50.240 --> 0:28:53.360
<v Speaker 4>than steroid nasal sprays because they're more specific. They're only

0:28:53.440 --> 0:28:57.680
<v Speaker 4>targeting the histamine rather than a more generalized inflammatory response.

0:28:57.760 --> 0:29:00.840
<v Speaker 4>The way that steroid nasal sprays are doesn't mean there's

0:29:00.840 --> 0:29:03.800
<v Speaker 4>no downside to steroid nasal sprays. The biggest side effect

0:29:03.840 --> 0:29:05.600
<v Speaker 4>tends to be that it can increase the risk of

0:29:05.640 --> 0:29:09.000
<v Speaker 4>nose bleeds for some people. Okay, and they usually take

0:29:09.040 --> 0:29:11.000
<v Speaker 4>some time to work, so they're not like automatic. It

0:29:11.040 --> 0:29:13.400
<v Speaker 4>takes several days for that steroid to build up in

0:29:13.440 --> 0:29:16.680
<v Speaker 4>your nasal passages to actually then reduce that inflammation.

0:29:17.160 --> 0:29:17.560
<v Speaker 1>Got it.

0:29:18.080 --> 0:29:22.240
<v Speaker 4>We use steroids also topically for things like egzema or

0:29:22.280 --> 0:29:27.520
<v Speaker 4>other allergic dermatitis type reactions, So topical ointments and creams

0:29:27.560 --> 0:29:31.800
<v Speaker 4>that contain steroids are phenomenal. But in terms of oral medications,

0:29:31.840 --> 0:29:36.160
<v Speaker 4>like we were talking about the scorched earth philosophy, Yeah, raw,

0:29:36.240 --> 0:29:39.280
<v Speaker 4>that's steroids, like right, they're just wiping out your entire

0:29:39.720 --> 0:29:46.760
<v Speaker 4>immune response indiscriminate exactly. So in cases of severe allergies

0:29:46.880 --> 0:29:49.560
<v Speaker 4>or a severe allergic reaction, then yes, there might be

0:29:49.640 --> 0:29:52.120
<v Speaker 4>like a short course of steroids, but they're really not

0:29:52.160 --> 0:29:55.920
<v Speaker 4>a great option for long term treatment for oral steroids.

0:29:56.720 --> 0:29:59.360
<v Speaker 4>Another honorable mention I will say it so that no

0:29:59.360 --> 0:30:01.320
<v Speaker 4>one gets mad that I didn't is a medicine called

0:30:01.440 --> 0:30:06.240
<v Speaker 4>Monte lucast singular is the brand name. Okay, it's controversial

0:30:06.360 --> 0:30:08.000
<v Speaker 4>enough that I'm not going to go into it, but

0:30:08.000 --> 0:30:11.920
<v Speaker 4>it's used mostly for asthma plus allergic rhinitis. So when

0:30:11.920 --> 0:30:16.080
<v Speaker 4>you have both of those things together, this, unlike anahistamines,

0:30:16.200 --> 0:30:22.040
<v Speaker 4>blocks another inflammatory bazouge called leukotrienes.

0:30:23.560 --> 0:30:26.840
<v Speaker 1>But isn't that you find it in the index of

0:30:26.880 --> 0:30:28.960
<v Speaker 1>a medical text book, right.

0:30:29.120 --> 0:30:32.600
<v Speaker 4>Yeah, it's one of the other things that your mass

0:30:32.640 --> 0:30:36.320
<v Speaker 4>cells spit out in the case of allergies, is a leucotriene,

0:30:36.520 --> 0:30:40.280
<v Speaker 4>and so this medication blocks some of those, but it

0:30:40.320 --> 0:30:42.480
<v Speaker 4>has a potential for more severe side effects, and we're

0:30:42.560 --> 0:30:47.920
<v Speaker 4>learning more about the neuropsychiatric potential side effects of this medication,

0:30:48.440 --> 0:30:53.040
<v Speaker 4>and so it is used, but not as commonly and

0:30:53.080 --> 0:30:56.160
<v Speaker 4>in very more specific indications compared to these other medicines

0:30:56.160 --> 0:31:03.040
<v Speaker 4>we're talking about today, okay, which include for the allergy shots. Yeah,

0:31:03.640 --> 0:31:06.360
<v Speaker 4>so how does an allergy shot work? Allergy shots are

0:31:06.400 --> 0:31:11.080
<v Speaker 4>something that we use really for again a wide range,

0:31:11.120 --> 0:31:15.280
<v Speaker 4>but an as far as all allergies go, a narrow subset.

0:31:15.320 --> 0:31:17.600
<v Speaker 4>And yet it is a wide range of different allergies,

0:31:18.160 --> 0:31:27.280
<v Speaker 4>mostly inhaled allergens, things like danders mites, cockroaches, pollens, also beastings,

0:31:27.520 --> 0:31:33.200
<v Speaker 4>fire ants, and other venoms. And this process most often

0:31:33.440 --> 0:31:40.120
<v Speaker 4>is done subcutaneously, so it's called subcutaneous immunotherapy SCI. And

0:31:40.240 --> 0:31:43.320
<v Speaker 4>essentially what happens is the person has to go usually weekly,

0:31:43.480 --> 0:31:46.360
<v Speaker 4>sometimes even more frequently like a couple times a week

0:31:46.400 --> 0:31:53.040
<v Speaker 4>to start, and an allergist will inject teeny tiny amounts

0:31:53.080 --> 0:31:56.720
<v Speaker 4>of the thing that they're allergic to underneath their skin.

0:31:57.120 --> 0:32:00.520
<v Speaker 1>It's just like iocane powder in The Princess Bride. But

0:32:00.640 --> 0:32:01.600
<v Speaker 1>it works.

0:32:02.240 --> 0:32:05.200
<v Speaker 4>I don't I have watched that movie, but I don't remember.

0:32:05.400 --> 0:32:07.719
<v Speaker 1>Can he's building up a tolerance to iyakane powder.

0:32:08.000 --> 0:32:10.320
<v Speaker 4>Oh okay, now I do remember.

0:32:10.520 --> 0:32:14.360
<v Speaker 1>Yeah, so he doesn't die and he puts it in

0:32:14.400 --> 0:32:15.320
<v Speaker 1>both of the drinks.

0:32:15.400 --> 0:32:18.000
<v Speaker 4>Yeah yeaheah, I do remember that now, thank you. It's

0:32:18.080 --> 0:32:21.719
<v Speaker 4>just like that, Aaron. That's how allergy shots it is,

0:32:22.080 --> 0:32:25.280
<v Speaker 4>literally what that is. So you start out weekly or

0:32:25.320 --> 0:32:28.320
<v Speaker 4>multiple times a week, and then you slowly are building

0:32:28.440 --> 0:32:31.480
<v Speaker 4>up the amount of allergen that this person's being exposed to,

0:32:32.200 --> 0:32:34.880
<v Speaker 4>and over time you space it out to less frequently

0:32:35.120 --> 0:32:38.320
<v Speaker 4>every couple of weeks, every month, every few months, and

0:32:38.360 --> 0:32:41.280
<v Speaker 4>this goes on for usually a couple of years, at

0:32:41.360 --> 0:32:45.640
<v Speaker 4>least many many months, and then eventually you can stop

0:32:45.720 --> 0:32:49.320
<v Speaker 4>doing the shots altogether and people don't have allergies or

0:32:49.440 --> 0:33:02.120
<v Speaker 4>have significantly less of a response to allergens.

0:33:11.120 --> 0:33:18.040
<v Speaker 1>Aaron, Why does that continuous exposure result in decrease sensitivity

0:33:18.120 --> 0:33:19.880
<v Speaker 1>rather than increase sensitivity.

0:33:20.280 --> 0:33:23.240
<v Speaker 4>It's a really good question. I think if we fully

0:33:23.480 --> 0:33:26.720
<v Speaker 4>understood why this works, then we'd have a lot better

0:33:26.760 --> 0:33:29.480
<v Speaker 4>treatment for all of our other allergies. And we don't.

0:33:29.720 --> 0:33:32.720
<v Speaker 4>But what we do know what is happening. So what

0:33:32.880 --> 0:33:36.880
<v Speaker 4>is happening is that this very minute, really really really

0:33:36.920 --> 0:33:42.600
<v Speaker 4>small amount but frequent and repeated exposure. What it does

0:33:42.960 --> 0:33:46.800
<v Speaker 4>is it kind of retrains our immune system and it

0:33:46.840 --> 0:33:51.560
<v Speaker 4>induces a level of tolerance. So the way that I

0:33:51.600 --> 0:33:55.800
<v Speaker 4>think of it is this repeated exposure over time trains

0:33:55.880 --> 0:33:58.840
<v Speaker 4>our immune system to be like, hey, listen, remember in

0:33:58.880 --> 0:34:01.200
<v Speaker 4>last week's episode, we talked about door number one and

0:34:01.240 --> 0:34:04.040
<v Speaker 4>door number two and how allergies they're opening too much

0:34:04.040 --> 0:34:07.680
<v Speaker 4>of door number two. So what this process is doing

0:34:07.800 --> 0:34:11.279
<v Speaker 4>is telling our immune system listen, like, we've opened up

0:34:11.400 --> 0:34:14.759
<v Speaker 4>enough of door number two. Like we've done it. It's overplayed.

0:34:15.120 --> 0:34:18.520
<v Speaker 4>Chill out with that over response. And then what our

0:34:18.560 --> 0:34:21.880
<v Speaker 4>immune system does is it starts to shift to the

0:34:21.920 --> 0:34:27.400
<v Speaker 4>production of IgA and IgG antibodies and away from the

0:34:27.400 --> 0:34:29.680
<v Speaker 4>production of IgE antibodies.

0:34:30.239 --> 0:34:32.279
<v Speaker 1>And what do IgA and IgG do.

0:34:32.920 --> 0:34:36.359
<v Speaker 4>Well, they don't trigger this mass cell type response, right.

0:34:36.640 --> 0:34:39.800
<v Speaker 4>It means that our bodies can still see and flag

0:34:39.880 --> 0:34:43.839
<v Speaker 4>these allergens because we have these other antibodies to them,

0:34:44.239 --> 0:34:47.799
<v Speaker 4>but we're never going to trigger that severe immune response

0:34:48.239 --> 0:34:51.320
<v Speaker 4>unless you have IgG antibodies. And so we are shifting

0:34:51.360 --> 0:34:53.640
<v Speaker 4>production to where we can be like, yes, immune system

0:34:54.080 --> 0:34:58.200
<v Speaker 4>recognize this, you can remember this allergen, but you don't

0:34:58.280 --> 0:35:00.000
<v Speaker 4>need to freak out about it.

0:35:00.400 --> 0:35:00.760
<v Speaker 1>Okay.

0:35:01.880 --> 0:35:07.880
<v Speaker 4>Unsurprisingly, this can also backfire and can induce anaphylaxis because

0:35:07.920 --> 0:35:11.520
<v Speaker 4>you are literally exposing somebody on purpose to something that

0:35:11.560 --> 0:35:14.840
<v Speaker 4>their body has already been trained to identify and attack.

0:35:15.280 --> 0:35:18.960
<v Speaker 4>So it's like Owen Grady is training velociraptors. That's like

0:35:19.040 --> 0:35:22.480
<v Speaker 4>the process of have you seen Jurassic Worlds?

0:35:22.880 --> 0:35:23.080
<v Speaker 3>No?

0:35:23.520 --> 0:35:25.919
<v Speaker 1>I just I stopped at Jurassic Park three.

0:35:26.280 --> 0:35:28.279
<v Speaker 4>Okay, well everyone else is going to know what I'm

0:35:28.320 --> 0:35:33.200
<v Speaker 4>talking about. Imagine someone trying to train a velociraptor, right, Like,

0:35:33.239 --> 0:35:35.960
<v Speaker 4>it might work because they're very smart, right, and so

0:35:36.040 --> 0:35:39.200
<v Speaker 4>they might learn, okay, don't attack this thing. But you

0:35:39.239 --> 0:35:41.600
<v Speaker 4>also could get your arm bit off. And that is

0:35:41.680 --> 0:35:44.880
<v Speaker 4>why allergy shots are always done in a very highly

0:35:44.920 --> 0:35:48.160
<v Speaker 4>regulated and monitored setting under direction of an allergist. And

0:35:48.200 --> 0:35:50.240
<v Speaker 4>it's not something that people do like at home.

0:35:50.280 --> 0:35:52.759
<v Speaker 1>Right, and you have to wait in the office and

0:35:52.800 --> 0:35:55.759
<v Speaker 1>make sure that's a certain amount of time. Yeah.

0:35:55.960 --> 0:35:59.759
<v Speaker 4>Now, there also are newer options to do this with

0:36:00.280 --> 0:36:03.839
<v Speaker 4>having to poke somebody, and this process is called sublingual.

0:36:03.960 --> 0:36:06.759
<v Speaker 4>Usually it's called sublingual immunotherapy, and that's when you are

0:36:06.760 --> 0:36:09.000
<v Speaker 4>exposed to the allergen under your tongue and so it

0:36:09.040 --> 0:36:11.400
<v Speaker 4>absorbs into your mucous membranes of your mouth rather than

0:36:11.480 --> 0:36:15.960
<v Speaker 4>under your skin. It's approved for some allergens, a smaller

0:36:16.040 --> 0:36:20.759
<v Speaker 4>subset of allergens than subcutaneous immunotherapy. And again we don't

0:36:20.760 --> 0:36:23.200
<v Speaker 4>know exactly why, but is it because like absorption isn't

0:36:23.200 --> 0:36:26.839
<v Speaker 4>as good whatever it is, We don't have as good

0:36:26.920 --> 0:36:31.160
<v Speaker 4>of protocols for all the allergens for sublingual immunotherapy, but

0:36:31.200 --> 0:36:33.640
<v Speaker 4>it is possible for some. So especially for kids, that's

0:36:33.680 --> 0:36:35.800
<v Speaker 4>a great option because getting shots is scary.

0:36:36.920 --> 0:36:39.520
<v Speaker 1>But you can't get shots for food allergies.

0:36:39.760 --> 0:36:44.040
<v Speaker 4>Oh aarin or can you white? Oh? Everything that I

0:36:44.120 --> 0:36:47.520
<v Speaker 4>just talked about. It's for the types of allergies that

0:36:47.680 --> 0:36:52.359
<v Speaker 4>mostly are like allergic rhinitis or rhinoconjunctivitis or venoms toxins.

0:36:52.960 --> 0:36:57.040
<v Speaker 4>It's not for food allergies. And it's not for lack

0:36:57.120 --> 0:37:00.520
<v Speaker 4>of trying. There have been so many studies where people

0:37:00.560 --> 0:37:05.000
<v Speaker 4>have tried to use subcutaneous immunotherapy or sublingual immunotherapy for

0:37:05.040 --> 0:37:09.440
<v Speaker 4>food allergies. They haven't panned out, mostly because especially with

0:37:09.480 --> 0:37:13.480
<v Speaker 4>subcutaneous people were just having really severe reactions. So like

0:37:13.520 --> 0:37:16.920
<v Speaker 4>the reactions were more severe and then more dangerous and

0:37:16.960 --> 0:37:22.919
<v Speaker 4>so nothing ever got approved. Asterisk because we'll talk more

0:37:22.960 --> 0:37:25.560
<v Speaker 4>at the end of this episode about some newer therapies

0:37:26.280 --> 0:37:29.680
<v Speaker 4>that are similar to this for food allergies.

0:37:30.480 --> 0:37:31.640
<v Speaker 1>Teaser. Wow.

0:37:31.760 --> 0:37:36.840
<v Speaker 4>I know, But until very very recently, like this year,

0:37:37.120 --> 0:37:41.400
<v Speaker 4>really the only real advice for people with food allergies

0:37:41.680 --> 0:37:44.320
<v Speaker 4>was avoid it, avoid it, avoid it, avoid it along

0:37:44.360 --> 0:37:48.000
<v Speaker 4>with an EpiPen, which brings us to our third and

0:37:48.040 --> 0:37:49.640
<v Speaker 4>final medication that we use to treat.

0:37:49.480 --> 0:37:52.719
<v Speaker 1>Allergies, epinephrine autoinjector. There you go.

0:37:56.280 --> 0:37:58.359
<v Speaker 4>I am really interested to hear the history of this.

0:37:59.000 --> 0:37:59.680
<v Speaker 1>It's a good one.

0:37:59.760 --> 0:38:01.239
<v Speaker 4>But what I'm going to talk about is like, what

0:38:01.280 --> 0:38:05.240
<v Speaker 4>the heck is in an EpiPen or an epinephrin autoinjector. Well,

0:38:05.680 --> 0:38:10.000
<v Speaker 4>it's epinephrine. That's easy, yep epinephrin. The other name for

0:38:10.040 --> 0:38:12.920
<v Speaker 4>it that people might have heard of is adrenaline, and

0:38:13.000 --> 0:38:16.239
<v Speaker 4>so epinephrin or adrenaline, it's literally the same thing, two

0:38:16.280 --> 0:38:16.920
<v Speaker 4>different names.

0:38:17.680 --> 0:38:20.000
<v Speaker 1>Why it's bizarre. I mean, it's like a little bit

0:38:20.000 --> 0:38:22.160
<v Speaker 1>in the history, but mostly it was just like someone

0:38:22.320 --> 0:38:23.920
<v Speaker 1>liked this and someone liked that.

0:38:23.920 --> 0:38:26.720
<v Speaker 4>That's what I figured. Two different people came up with that. Again, Yeah,

0:38:26.840 --> 0:38:29.839
<v Speaker 4>we picked one This is a hormone that we make

0:38:29.880 --> 0:38:33.840
<v Speaker 4>in our bodies. And this hormone is our like fighter

0:38:34.000 --> 0:38:38.319
<v Speaker 4>flight hormone. It's our fight or flight response hormone. So

0:38:38.480 --> 0:38:41.440
<v Speaker 4>epiephyrine is the thing that makes your heart pound when

0:38:41.480 --> 0:38:44.200
<v Speaker 4>you get anxious. It's the thing that makes you feel

0:38:44.320 --> 0:38:47.319
<v Speaker 4>jittery when you're feeling jittery when you're anxious, or when

0:38:47.320 --> 0:38:51.400
<v Speaker 4>you're nervous, or when you're super excited. Epinephrin acts on

0:38:51.480 --> 0:38:54.560
<v Speaker 4>these receptors in our body across our entire body, called

0:38:54.680 --> 0:38:58.440
<v Speaker 4>alpha receptors, and these receptors are present on our blood

0:38:58.480 --> 0:39:04.000
<v Speaker 4>vessels and they so to constrict our blood vessels. Anaphylaxis,

0:39:04.040 --> 0:39:06.920
<v Speaker 4>like we talked about last week, dilates our blood vessels,

0:39:07.320 --> 0:39:11.720
<v Speaker 4>so when we give this drug, we constrict them boom logic.

0:39:12.760 --> 0:39:15.640
<v Speaker 4>But epinephrin does even more than that. It also works

0:39:15.719 --> 0:39:19.360
<v Speaker 4>on these receptors called beta receptors, and we have a

0:39:19.400 --> 0:39:22.880
<v Speaker 4>lot of these on our heart. And when epinephrin binds

0:39:23.080 --> 0:39:25.959
<v Speaker 4>to these receptors on our heart, it makes our heart

0:39:26.000 --> 0:39:30.399
<v Speaker 4>beat faster, and it makes our heart beat harder, so

0:39:30.440 --> 0:39:36.280
<v Speaker 4>it's pumping blood through these more narrowed vessels. It also

0:39:36.719 --> 0:39:40.920
<v Speaker 4>through these beta receptors in our lungs, relaxes the muscles

0:39:40.920 --> 0:39:45.200
<v Speaker 4>in our airways to reverse that broncho constriction or bronchospasm

0:39:45.239 --> 0:39:51.640
<v Speaker 4>that we see. So that is why epinephrine is the medicine.

0:39:51.680 --> 0:39:56.400
<v Speaker 4>It is the medicine to treat anaphylaxis. Like, point blank period,

0:39:56.600 --> 0:39:59.279
<v Speaker 4>this is what you use. Okay, I kind of have

0:39:59.360 --> 0:40:01.439
<v Speaker 4>a silly there's no such thing.

0:40:01.680 --> 0:40:04.319
<v Speaker 1>Okay. Well, so let's say that you know that you

0:40:04.360 --> 0:40:08.680
<v Speaker 1>are really really allergic to beastings and you see a bee.

0:40:09.360 --> 0:40:12.399
<v Speaker 1>Presumably does that mean that you're adrenaline would shoot up?

0:40:13.080 --> 0:40:16.800
<v Speaker 1>Would that make you less likely to have an anaphylactic reaction?

0:40:17.520 --> 0:40:19.600
<v Speaker 4>Aaron, that's not a silly question. That is such a

0:40:19.640 --> 0:40:20.520
<v Speaker 4>fun question.

0:40:21.000 --> 0:40:22.440
<v Speaker 1>Or like a snake bite. You see a snake and

0:40:22.480 --> 0:40:24.799
<v Speaker 1>you're like, ah, and then it bites you, and you're

0:40:24.920 --> 0:40:26.759
<v Speaker 1>freaked out that the snake bit you, and then your

0:40:26.760 --> 0:40:29.320
<v Speaker 1>body is like anaphyl access time, and then your body's

0:40:29.320 --> 0:40:30.680
<v Speaker 1>also like but we just saw a snake.

0:40:30.800 --> 0:40:35.120
<v Speaker 4>So Aaron, this is such a fun question in the

0:40:35.120 --> 0:40:37.960
<v Speaker 4>context of the history, and like the toxin hypothesis from

0:40:38.040 --> 0:40:42.000
<v Speaker 4>last week. Yeah, I have no idea.

0:40:41.480 --> 0:40:43.520
<v Speaker 1>I have no idea either.

0:40:46.200 --> 0:40:49.279
<v Speaker 4>I have absolutely no idea. I like, I don't even

0:40:49.280 --> 0:40:52.160
<v Speaker 4>know how you would study that, Like if someone is

0:40:52.560 --> 0:40:56.440
<v Speaker 4>anxious before they Yeah, I have no idea how you

0:40:56.440 --> 0:40:58.960
<v Speaker 4>would study that because we can't even do like placebo

0:40:59.000 --> 0:41:02.360
<v Speaker 4>controlled trials on epinephrine because it would be unethical.

0:41:03.960 --> 0:41:12.600
<v Speaker 1>And how durable is an adrenaline spike, right versus the anaphylaxis, etcetera?

0:41:13.080 --> 0:41:16.759
<v Speaker 4>Right? And is it just that in anaphylaxis do you

0:41:16.960 --> 0:41:21.200
<v Speaker 4>just not have enough endogenous adrenaline? Are you just not

0:41:21.320 --> 0:41:24.959
<v Speaker 4>making enough epinephrin? And that is why, right, Because here's

0:41:24.960 --> 0:41:27.440
<v Speaker 4>the other thing, and this is where epiephrin gets a

0:41:27.440 --> 0:41:31.840
<v Speaker 4>little bit weird. These beta receptors they also do vasodilation,

0:41:32.000 --> 0:41:37.160
<v Speaker 4>which is what is happening in anaphylaxis. So if you

0:41:37.239 --> 0:41:40.200
<v Speaker 4>give someone some epiephrin but not enough, like a lower

0:41:40.239 --> 0:41:43.640
<v Speaker 4>dose of it, then those effects can override and be

0:41:43.760 --> 0:41:48.200
<v Speaker 4>stronger than the vaso constriction effects on the alpha receptors.

0:41:48.520 --> 0:41:52.960
<v Speaker 4>And so the dose is actually really important in epinephrine.

0:41:53.160 --> 0:41:56.840
<v Speaker 1>Okay, So each EpiPen contains a dose specific to the

0:41:56.880 --> 0:41:58.719
<v Speaker 1>person that it is prescribed for.

0:41:58.920 --> 0:42:03.200
<v Speaker 4>Absolutely not aaron be personalized medicine, and we don't have that. Wait,

0:42:03.680 --> 0:42:08.200
<v Speaker 4>so an epinephrin autoinjector EpiPen. I will throw out other

0:42:08.239 --> 0:42:12.759
<v Speaker 4>trade names and a penn emorad fast jecked that's what

0:42:12.840 --> 0:42:17.799
<v Speaker 4>one is called in German. Love that these devices are

0:42:18.440 --> 0:42:23.080
<v Speaker 4>fixed dose injectors in the US, they're mostly in two doses.

0:42:23.160 --> 0:42:26.760
<v Speaker 4>For kids they're point one five milligrams and for adults

0:42:26.800 --> 0:42:29.919
<v Speaker 4>they're point three milligrams. That's it. Those are the two

0:42:29.960 --> 0:42:33.120
<v Speaker 4>dose options, and you get prescribed them based on weight.

0:42:33.239 --> 0:42:35.040
<v Speaker 4>So babies and small kids are going to get the

0:42:35.040 --> 0:42:37.000
<v Speaker 4>small dose. Everyone else is going to get the big dose,

0:42:37.000 --> 0:42:41.279
<v Speaker 4>which means some people might be overdosed, some people might

0:42:41.320 --> 0:42:45.479
<v Speaker 4>be underdosed. But across the board, I know your face

0:42:45.560 --> 0:42:48.800
<v Speaker 4>is like, that sounds horrible. Why yeah, But it's also

0:42:49.120 --> 0:42:52.759
<v Speaker 4>like across the board, even though there are potential side effects,

0:42:53.520 --> 0:42:56.600
<v Speaker 4>how long ago side effects last are usually not that long.

0:42:57.000 --> 0:42:59.400
<v Speaker 4>And so these are the doses that are considered across

0:42:59.400 --> 0:43:01.839
<v Speaker 4>the board safe. And so you give the dose that

0:43:02.160 --> 0:43:04.799
<v Speaker 4>is closest to that person's weight based on their weight.

0:43:05.480 --> 0:43:08.839
<v Speaker 1>Why would we not have a finer system for doing this?

0:43:09.280 --> 0:43:11.480
<v Speaker 4>Oh my gosh, Arin, that is a question for pharmaceutical

0:43:11.560 --> 0:43:13.799
<v Speaker 4>companies and who's making the most money off of.

0:43:13.760 --> 0:43:18.240
<v Speaker 1>This, and there's already price gouging going on, like yeah,

0:43:18.320 --> 0:43:22.520
<v Speaker 1>with EpiPens or epinephrin autoinjectors. Excuse me, I don't know

0:43:22.560 --> 0:43:25.600
<v Speaker 1>which companies are doing the price gouging, but does happen?

0:43:27.280 --> 0:43:30.000
<v Speaker 4>I don't have an answer to that. But these doses

0:43:30.040 --> 0:43:32.920
<v Speaker 4>work for most people. When I say like underdose or overdose,

0:43:32.960 --> 0:43:36.359
<v Speaker 4>it's not a large segment of the population. It's more

0:43:36.480 --> 0:43:39.200
<v Speaker 4>likely that somebody might be underdosed, but at least you're

0:43:39.239 --> 0:43:40.279
<v Speaker 4>still buying time.

0:43:41.080 --> 0:43:41.360
<v Speaker 1>Okay.

0:43:41.360 --> 0:43:44.719
<v Speaker 4>It's also the case that many people, regardless of whether

0:43:44.760 --> 0:43:47.080
<v Speaker 4>it was the perfect like weight based dose or not,

0:43:47.640 --> 0:43:51.040
<v Speaker 4>might need more than one because this epiphyrin doesn't last

0:43:51.120 --> 0:43:55.319
<v Speaker 4>for very long. The effects are very rapid onset but transient,

0:43:55.719 --> 0:43:58.600
<v Speaker 4>and so a lot of times they will help, but

0:43:58.640 --> 0:44:01.640
<v Speaker 4>then that's not enough going to need multiple doses. People

0:44:01.719 --> 0:44:05.040
<v Speaker 4>might even need an infusion of epinephrin running over a

0:44:05.080 --> 0:44:08.360
<v Speaker 4>really long time period, like multiple hours, before their body

0:44:08.440 --> 0:44:09.640
<v Speaker 4>is really out of the woods.

0:44:10.239 --> 0:44:11.520
<v Speaker 1>Wow. Yeah.

0:44:11.640 --> 0:44:15.040
<v Speaker 4>So in general, one of the benefits of these autoinjectors

0:44:15.120 --> 0:44:17.880
<v Speaker 4>is that they are standardized across the board, so no

0:44:18.000 --> 0:44:21.279
<v Speaker 4>matter what pen you can find, if someone needs one,

0:44:21.360 --> 0:44:24.320
<v Speaker 4>you can use it right it's the same dose for everyone,

0:44:24.560 --> 0:44:28.120
<v Speaker 4>so it's easy in that way. They're also designed to

0:44:28.200 --> 0:44:31.800
<v Speaker 4>deliver the epinephrin directly into the muscle, and we usually

0:44:31.880 --> 0:44:35.600
<v Speaker 4>use the thigh muscle because it's a nice, juicy, beefy

0:44:35.760 --> 0:44:40.200
<v Speaker 4>muscle that has a ton of really good blood vessels

0:44:40.239 --> 0:44:43.279
<v Speaker 4>and really good blood supply, which means that the epinephrin

0:44:43.320 --> 0:44:47.200
<v Speaker 4>gets delivered in a really predictable way to the blood

0:44:47.920 --> 0:44:51.000
<v Speaker 4>as opposed to intravenous, which you can have much higher

0:44:51.040 --> 0:44:53.399
<v Speaker 4>side effects. Plus then you have to find somebody's vein,

0:44:53.480 --> 0:44:58.680
<v Speaker 4>which in an emergency isn't easy to do, and subcutaneous administration,

0:44:58.800 --> 0:45:01.120
<v Speaker 4>so just putting it into the se skin or like

0:45:01.239 --> 0:45:04.239
<v Speaker 4>just under the skin rather than into the muscle. What

0:45:04.280 --> 0:45:09.040
<v Speaker 4>happens is that you have so much local vasoconstriction from

0:45:09.120 --> 0:45:13.040
<v Speaker 4>the medicine that you don't have as much penetration quickly

0:45:13.080 --> 0:45:15.479
<v Speaker 4>into the bloodstream, so it doesn't work quite as well.

0:45:15.719 --> 0:45:16.960
<v Speaker 4>Still better than nothing.

0:45:16.960 --> 0:45:20.200
<v Speaker 1>And seconds matter, like, yeah, seconds absolutely matter. Yeah.

0:45:20.440 --> 0:45:23.680
<v Speaker 4>These pens also are designed to work through clothing, so

0:45:23.719 --> 0:45:26.160
<v Speaker 4>they can be delivered incredibly rapidly. You don't have to

0:45:26.160 --> 0:45:29.399
<v Speaker 4>worry about like exposing someone's thigh. You just can get

0:45:29.400 --> 0:45:30.400
<v Speaker 4>the medicine.

0:45:29.960 --> 0:45:33.160
<v Speaker 1>In how do you know when to use one?

0:45:33.680 --> 0:45:37.960
<v Speaker 4>That is a really good question, Aaron, and that is

0:45:40.080 --> 0:45:42.239
<v Speaker 4>it is not something I can fully answer. But and

0:45:42.280 --> 0:45:44.480
<v Speaker 4>there have also been studies and there's a paper that

0:45:44.520 --> 0:45:47.520
<v Speaker 4>I'll link to in our sources about like pros and

0:45:47.600 --> 0:45:50.680
<v Speaker 4>cons of at what point in an allergic response, like

0:45:50.719 --> 0:45:52.840
<v Speaker 4>do you wait for things to get more severe or

0:45:52.840 --> 0:45:56.359
<v Speaker 4>do you not? And the thing is that even when

0:45:56.400 --> 0:45:59.360
<v Speaker 4>there are cases where yeah, maybe you could have weighted,

0:46:00.400 --> 0:46:05.799
<v Speaker 4>the side effects of epinephrine generally are less severe than

0:46:05.840 --> 0:46:09.440
<v Speaker 4>the risks of waiting. So usually across the board, the

0:46:09.480 --> 0:46:12.799
<v Speaker 4>recommendation is if you have a known like especially if

0:46:12.840 --> 0:46:16.319
<v Speaker 4>you've ever had anaphylaxis before, or if you have had

0:46:16.440 --> 0:46:19.839
<v Speaker 4>severe enough reactions where maybe it's not anaphylaxis, but you're

0:46:19.880 --> 0:46:23.200
<v Speaker 4>really at high risk of anaphylaxis, then the recommendation is

0:46:23.280 --> 0:46:26.440
<v Speaker 4>once you see signs of a systemic response and not

0:46:26.800 --> 0:46:29.879
<v Speaker 4>just like oh, just one hive or something like that,

0:46:30.760 --> 0:46:35.160
<v Speaker 4>then you give it, because the risks of waiting often

0:46:35.239 --> 0:46:38.520
<v Speaker 4>outweigh the risks of the medication itself.

0:46:39.040 --> 0:46:40.760
<v Speaker 1>Okay, but again it's.

0:46:40.600 --> 0:46:44.480
<v Speaker 4>Gonna be I'm not your doctor, so this is not

0:46:44.600 --> 0:46:48.960
<v Speaker 4>medical advice. Also not medical advice. I feel very strongly

0:46:49.000 --> 0:46:51.600
<v Speaker 4>that everybody should learn how to use one of these pens,

0:46:51.640 --> 0:46:54.640
<v Speaker 4>even if you don't have allergies, because allergies are so common.

0:46:55.160 --> 0:46:57.359
<v Speaker 4>So there's lots of great YouTube videos out there. Most

0:46:57.360 --> 0:46:59.400
<v Speaker 4>of them are really similar, even though all the pens

0:46:59.440 --> 0:47:01.520
<v Speaker 4>look different. Some look like a box, some look like

0:47:01.520 --> 0:47:05.399
<v Speaker 4>a pen. Never ever, ever, ever put your finger over

0:47:05.440 --> 0:47:09.239
<v Speaker 4>the top anyone. You hold it like it's a I

0:47:09.280 --> 0:47:14.480
<v Speaker 4>don't know, a turkey leg, not.

0:47:14.440 --> 0:47:18.760
<v Speaker 1>Like a I honestly, I can't think of anything else

0:47:18.960 --> 0:47:21.799
<v Speaker 1>that's perfect, thank you. Why you hold a turkey leg.

0:47:21.880 --> 0:47:23.200
<v Speaker 1>You're not going to hold it with like You're not

0:47:23.239 --> 0:47:25.239
<v Speaker 1>going to hold it like end over the top of

0:47:25.239 --> 0:47:25.880
<v Speaker 1>the time, and.

0:47:25.880 --> 0:47:28.000
<v Speaker 4>Over the top. You can you can die that way anyways.

0:47:29.239 --> 0:47:34.440
<v Speaker 4>And we'll talk more about other newer options for epinephrine administration,

0:47:35.000 --> 0:47:37.839
<v Speaker 4>because also injecting your like shoving a needle into your

0:47:37.880 --> 0:47:43.359
<v Speaker 4>leg or your child's leg, that's traumatic. Yea, So there

0:47:43.400 --> 0:47:47.080
<v Speaker 4>are some really awesome newer options. But one of the

0:47:47.120 --> 0:47:51.440
<v Speaker 4>biggest issues you mentioned cost Aaron. These pens can be

0:47:51.520 --> 0:47:54.799
<v Speaker 4>incredibly expensive. I went on good RX and I looked

0:47:54.800 --> 0:47:56.319
<v Speaker 4>them up, and the cheapest one I could find in

0:47:56.360 --> 0:47:59.600
<v Speaker 4>the US is one hundred and forty dollars for two pens.

0:48:00.040 --> 0:48:02.399
<v Speaker 4>If you don't have insurance or if your insurance doesn't cover,

0:48:02.800 --> 0:48:03.600
<v Speaker 4>that's not cheap.

0:48:03.719 --> 0:48:04.480
<v Speaker 1>No, it's not cheap.

0:48:04.520 --> 0:48:07.239
<v Speaker 4>But an even bigger problem in terms of access is that,

0:48:07.280 --> 0:48:10.920
<v Speaker 4>according to the World Allergy Organization of a survey of

0:48:11.040 --> 0:48:15.239
<v Speaker 4>all of its member states, this type of epinephrine autoinjector

0:48:15.320 --> 0:48:18.239
<v Speaker 4>is only available in sixty percent of the countries that

0:48:18.280 --> 0:48:20.080
<v Speaker 4>they surveyed sixty percent.

0:48:20.440 --> 0:48:23.040
<v Speaker 1>And then I would still imagine, like you know, we

0:48:23.200 --> 0:48:24.919
<v Speaker 1>talked about, oh do you wait? Do you not wait?

0:48:25.120 --> 0:48:27.480
<v Speaker 1>How do you know when to? And I wonder for

0:48:27.520 --> 0:48:30.319
<v Speaker 1>how many people. Cost is a factor in them one.

0:48:30.280 --> 0:48:33.319
<v Speaker 4>Hundred percent because then if you use it, and they

0:48:33.360 --> 0:48:36.000
<v Speaker 4>also degrade within twelve to eighteen months, so they have

0:48:36.080 --> 0:48:38.040
<v Speaker 4>to be replaced, so you need a new one. Even

0:48:38.040 --> 0:48:40.400
<v Speaker 4>if you don't use it, you have to carry it

0:48:40.440 --> 0:48:44.719
<v Speaker 4>with you all of the time because you have no

0:48:44.840 --> 0:48:47.560
<v Speaker 4>idea when you might be exposed to something that could

0:48:47.560 --> 0:48:50.759
<v Speaker 4>give you an anaphylactic reaction. I mean, it's it is.

0:48:51.800 --> 0:48:54.640
<v Speaker 4>They are life saving medication and it is incredible and

0:48:54.719 --> 0:48:57.520
<v Speaker 4>we need better options and more affordable options. So we'll

0:48:57.560 --> 0:49:01.520
<v Speaker 4>talk about that a little later. But Aaron, first, tell

0:49:01.560 --> 0:49:03.919
<v Speaker 4>me how did we come up with all of these

0:49:03.960 --> 0:49:04.960
<v Speaker 4>different medications?

0:49:06.719 --> 0:49:10.040
<v Speaker 1>Yeah, there's a lot of story to cover, so let's

0:49:10.040 --> 0:49:48.000
<v Speaker 1>take a break and then I'll get started. If you

0:49:48.040 --> 0:49:51.400
<v Speaker 1>look in my bathroom cabinet, you will find, among a

0:49:51.480 --> 0:49:55.520
<v Speaker 1>million other things like cough drops and ibuprofen, about ten

0:49:55.600 --> 0:49:58.239
<v Speaker 1>different types of anahistamine medications.

0:49:58.480 --> 0:49:59.439
<v Speaker 4>Wow, that's a lot.

0:49:59.560 --> 0:50:03.160
<v Speaker 1>It's a lot. Yeah, drowsy, non drowsy, generic name brand

0:50:03.280 --> 0:50:06.839
<v Speaker 1>in a cold medicine combo. Ten is I don't really

0:50:06.920 --> 0:50:09.319
<v Speaker 1>think it's an exaggeration. Maybe it's more like eight, but

0:50:09.360 --> 0:50:12.839
<v Speaker 1>it's it's honestly, there's a lot. I'm ready for when

0:50:12.840 --> 0:50:16.000
<v Speaker 1>someone visits during ragweed season and asks if we have

0:50:16.120 --> 0:50:19.319
<v Speaker 1>any cleraton or walletin which is what we actually have?

0:50:19.440 --> 0:50:21.560
<v Speaker 1>Which is the question?

0:50:21.760 --> 0:50:22.000
<v Speaker 3>Brand?

0:50:22.239 --> 0:50:25.319
<v Speaker 1>No, it's Walgreens, Okay. I don't know if we would

0:50:25.360 --> 0:50:29.960
<v Speaker 1>go through a Costco size thing of Clareton Costco Allertech.

0:50:29.560 --> 0:50:33.320
<v Speaker 4>Have gone through many many a bottle of Children's Alertech.

0:50:35.280 --> 0:50:38.160
<v Speaker 1>My husband gets allergy shots every Saturday. I think he's

0:50:38.200 --> 0:50:40.520
<v Speaker 1>actually down to every other Saturday because they seem to

0:50:40.560 --> 0:50:44.320
<v Speaker 1>be helping. Yep. And while I don't personally own an EpiPen.

0:50:44.640 --> 0:50:47.680
<v Speaker 1>I probably should, just in case I have family and

0:50:47.719 --> 0:50:51.840
<v Speaker 1>friends who do. Considering the extremely high prevalence of allergies

0:50:51.920 --> 0:50:55.799
<v Speaker 1>around the globe, it's not all that surprising that medicine

0:50:55.920 --> 0:50:59.760
<v Speaker 1>has put together a stocked and diverse toolkit for dealing

0:51:00.120 --> 0:51:04.080
<v Speaker 1>with this condition. But it is pretty amazing even considering

0:51:04.120 --> 0:51:07.960
<v Speaker 1>the limitations of these treatments, because even though allergies were

0:51:08.000 --> 0:51:11.200
<v Speaker 1>only described and linked to an exposure roughly one hundred

0:51:11.200 --> 0:51:14.080
<v Speaker 1>and fifty years ago, even though we don't have a

0:51:14.160 --> 0:51:17.560
<v Speaker 1>full grasp on why we develop allergies in the first

0:51:17.600 --> 0:51:20.960
<v Speaker 1>place and how to prevent them entirely, we do have

0:51:21.160 --> 0:51:25.480
<v Speaker 1>effective treatments and plenty more promising ones on the horizon.

0:51:26.239 --> 0:51:28.600
<v Speaker 1>So what I want to do today is talk about

0:51:28.640 --> 0:51:31.920
<v Speaker 1>the big three, as we've already discussed, to pay them

0:51:31.960 --> 0:51:35.680
<v Speaker 1>homage right in order of their development. So we'll start

0:51:35.719 --> 0:51:40.759
<v Speaker 1>with allergy immunotherapy aka allergy shots I know are theomulars

0:51:40.920 --> 0:51:47.480
<v Speaker 1>I know, and histamines and epinephrine auto injectors aka your EpiPens. Okay,

0:51:47.680 --> 0:51:50.680
<v Speaker 1>and let me just acknowledge that these treatments are not perfect, right,

0:51:50.760 --> 0:51:53.280
<v Speaker 1>They don't work for everyone, they aren't the only ones

0:51:53.320 --> 0:51:56.680
<v Speaker 1>out there, and there is certainly room for improvement, because

0:51:56.719 --> 0:52:00.520
<v Speaker 1>allergy remains a debilitating condition for many people, even with

0:52:00.560 --> 0:52:04.239
<v Speaker 1>these treatments available, or even with the threat of allergies

0:52:04.320 --> 0:52:08.920
<v Speaker 1>out there. Right. But in most respects allergy treatment is

0:52:09.000 --> 0:52:12.359
<v Speaker 1>a huge medical success story, and it's one that I'm

0:52:12.400 --> 0:52:17.920
<v Speaker 1>excited to tell in three chapters, Chapter one, Thank You Vaccines.

0:52:20.360 --> 0:52:23.560
<v Speaker 1>In last week's episode, I mentioned that English physician John

0:52:23.640 --> 0:52:27.040
<v Speaker 1>Bostock was the first to describe allergy in eighteen nineteen

0:52:27.160 --> 0:52:30.320
<v Speaker 1>hay fever, and that it was Charles Blackley in eighteen

0:52:30.400 --> 0:52:34.000
<v Speaker 1>seventy who first linked hay fever to a specific exposure,

0:52:34.080 --> 0:52:38.200
<v Speaker 1>in this case, grass pollen. Blackley's evidence was pretty compelling.

0:52:38.719 --> 0:52:41.800
<v Speaker 1>He stuck grass pollen up his nose out of season

0:52:42.040 --> 0:52:45.920
<v Speaker 1>to show that it still caused symptoms. He correlated pollen

0:52:46.000 --> 0:52:50.000
<v Speaker 1>counts with prevalence and severity of hay fever symptoms, and

0:52:50.239 --> 0:52:54.120
<v Speaker 1>his conclusions were simultaneously corroborated by a physician in the

0:52:54.239 --> 0:52:59.120
<v Speaker 1>US who was inhaling ragweed to induce his symptoms. Wow,

0:52:59.360 --> 0:53:04.160
<v Speaker 1>sounds really pleasant, right, It's hardcore, like for you, very hardcore.

0:53:04.400 --> 0:53:06.480
<v Speaker 4>Would not subject myself to that. Sorry.

0:53:08.120 --> 0:53:11.680
<v Speaker 1>Despite this, many scientists still doubted that grass pollen could

0:53:11.680 --> 0:53:14.040
<v Speaker 1>cause such a response, and that it must be some

0:53:14.280 --> 0:53:20.040
<v Speaker 1>undescribed microbe or good old hysteria. Fortunately, others were convinced

0:53:20.160 --> 0:53:24.359
<v Speaker 1>enough to take matters into their own hands, like William Dunbar, who,

0:53:24.520 --> 0:53:28.200
<v Speaker 1>as a hay fever sufferer himself, was personally invested in

0:53:28.360 --> 0:53:34.400
<v Speaker 1>understanding what caused his seasonal symptoms. So Dunbar confirmed Blackley's

0:53:34.440 --> 0:53:39.640
<v Speaker 1>findings by injecting undiluted grass pollen extract into himself and

0:53:39.680 --> 0:53:42.880
<v Speaker 1>his colleague, who also had hay fever. It's just like

0:53:43.920 --> 0:53:47.320
<v Speaker 1>a shot of undiluted, straight up grasp polowing.

0:53:48.520 --> 0:53:49.560
<v Speaker 4>He was miserable.

0:53:49.840 --> 0:53:53.600
<v Speaker 1>Yeah, yeah, both both he and his colleague had awful

0:53:54.000 --> 0:53:58.960
<v Speaker 1>systemic reactions like I can't imagine. And instead of that

0:53:59.080 --> 0:54:03.600
<v Speaker 1>experience persuading them from pursuing this area of study, they

0:54:03.600 --> 0:54:07.080
<v Speaker 1>were like, more, we must keep doing this.

0:54:07.400 --> 0:54:08.080
<v Speaker 4>Oh my god.

0:54:09.000 --> 0:54:11.400
<v Speaker 1>And granted they didn't inject themselves with like full on

0:54:11.480 --> 0:54:16.440
<v Speaker 1>pollen again. Instead, they took the diphtheria antitoxin approach, and

0:54:16.480 --> 0:54:20.799
<v Speaker 1>they tried to produce pollen anti serum by injecting horses

0:54:20.920 --> 0:54:21.840
<v Speaker 1>with grass pollen.

0:54:22.480 --> 0:54:23.320
<v Speaker 4>Huh.

0:54:23.400 --> 0:54:26.040
<v Speaker 1>They then turned the serum into powder which could be

0:54:26.080 --> 0:54:30.200
<v Speaker 1>applied to the eyes and nose prophylactically during hay fever season.

0:54:30.800 --> 0:54:31.520
<v Speaker 4>Did it work?

0:54:32.280 --> 0:54:36.240
<v Speaker 1>Results were mixed, okay, some people got worse. They developed

0:54:36.239 --> 0:54:39.319
<v Speaker 1>a sensitivity to the horse serum itself, something that had

0:54:39.320 --> 0:54:43.799
<v Speaker 1>been known to happen with other serum antitoxins. Dunbar didn't

0:54:43.800 --> 0:54:45.799
<v Speaker 1>give up hope, though, and he took one of these

0:54:45.840 --> 0:54:49.400
<v Speaker 1>patients who had developed this sensitivity and started them on

0:54:49.440 --> 0:54:54.560
<v Speaker 1>a pallen exposure journey. Over many weeks, he injected teeny

0:54:54.640 --> 0:54:58.480
<v Speaker 1>tiny amounts of grass pollen extract alternating with horse serum,

0:54:58.880 --> 0:55:01.880
<v Speaker 1>trying to get them dec sensitized to both, and at

0:55:01.920 --> 0:55:05.440
<v Speaker 1>the end of fifteen increasing dosages, the patient had become

0:55:05.600 --> 0:55:09.720
<v Speaker 1>much more tolerant of pollen. During that first hay fever season,

0:55:09.760 --> 0:55:13.120
<v Speaker 1>they reported much more mild symptoms compared to previous years.

0:55:13.640 --> 0:55:14.319
<v Speaker 4>Wow.

0:55:15.000 --> 0:55:18.920
<v Speaker 1>Dunbar published his results in nineteen oh three. Nineteen oh

0:55:18.960 --> 0:55:24.320
<v Speaker 1>three wow right, and he wasn't even necessarily the first

0:55:24.360 --> 0:55:27.120
<v Speaker 1>to try out this concept. A few other small reports

0:55:27.120 --> 0:55:30.000
<v Speaker 1>came out in a five or so years before, but

0:55:30.080 --> 0:55:32.799
<v Speaker 1>it was Dunbar's paper that would catch the eye of

0:55:32.840 --> 0:55:37.120
<v Speaker 1>one young researcher, Leonard Noon. Noon was on board with

0:55:37.160 --> 0:55:41.960
<v Speaker 1>hay fever being caused by grass pollen, specifically quote, a

0:55:42.000 --> 0:55:45.480
<v Speaker 1>soluble toxin found in the pollen of grasses. It is

0:55:45.560 --> 0:55:49.160
<v Speaker 1>also undoubted that hay fever patients sometimes become cured of

0:55:49.160 --> 0:55:53.560
<v Speaker 1>their idiosyncrasy. The most reasonable explanation of this phenomenon would

0:55:53.560 --> 0:55:56.200
<v Speaker 1>seem to be that the cured patients have had the

0:55:56.200 --> 0:55:59.840
<v Speaker 1>good fortune to develop an active immunity against the toxin

0:56:00.160 --> 0:56:02.719
<v Speaker 1>to the action of which they have been liable for

0:56:02.760 --> 0:56:04.360
<v Speaker 1>so long end quote.

0:56:04.760 --> 0:56:08.160
<v Speaker 4>I love this, Aaron, and so.

0:56:08.320 --> 0:56:12.920
<v Speaker 1>Using this logic, Noon rounded up some human volunteers and

0:56:13.040 --> 0:56:16.399
<v Speaker 1>tested their sensitivity to pollen by dropping a little bit

0:56:16.400 --> 0:56:21.120
<v Speaker 1>of pollen extract into their eye. Sounds horrible. And also

0:56:21.520 --> 0:56:23.919
<v Speaker 1>I just wanted to note that the pollen had been

0:56:23.960 --> 0:56:27.640
<v Speaker 1>collected by his sister, which I just love, Like, I

0:56:27.680 --> 0:56:29.239
<v Speaker 1>love that detail so much.

0:56:29.360 --> 0:56:32.359
<v Speaker 4>He's like, hess, go out, no, no, no, in this grat,

0:56:32.560 --> 0:56:35.359
<v Speaker 4>just this subcrat. Okay that collected at all? Just like,

0:56:35.480 --> 0:56:36.719
<v Speaker 4>just bring it back to me. It's cool. He is

0:56:36.760 --> 0:56:38.000
<v Speaker 4>a glass tube, is fine.

0:56:38.280 --> 0:56:44.960
<v Speaker 1>Yeah. And then in the winter and spring, outside of

0:56:45.000 --> 0:56:49.680
<v Speaker 1>hay fever season, he proceeded to administer very precise doses

0:56:49.800 --> 0:56:52.799
<v Speaker 1>of this pollen extract to his two groups. Those with

0:56:53.040 --> 0:56:56.400
<v Speaker 1>and those without hay fever, and he increased the concentration

0:56:56.600 --> 0:57:00.759
<v Speaker 1>of these doses slowly over the weeks. He experimented with

0:57:00.800 --> 0:57:05.120
<v Speaker 1>different intervals between injections and found that longer intervals could

0:57:05.160 --> 0:57:09.960
<v Speaker 1>actually make the patient become resensitized, and shorter intervals seemed

0:57:10.000 --> 0:57:16.280
<v Speaker 1>to meaningfully reduce symptoms. Unfortunately, Nune was not able to

0:57:16.320 --> 0:57:19.800
<v Speaker 1>see his experiment to the full conclusion, nor would he

0:57:19.880 --> 0:57:23.200
<v Speaker 1>live to see his landmark research honored in the decades

0:57:23.240 --> 0:57:29.400
<v Speaker 1>to come as the first allergen immunotherapy trial. None had tuberculosis,

0:57:29.960 --> 0:57:32.760
<v Speaker 1>and over the course of the study he grew sicker

0:57:32.800 --> 0:57:35.520
<v Speaker 1>and sicker, and he eventually had to turn his work

0:57:35.560 --> 0:57:39.800
<v Speaker 1>over to his friend John Freeman to finish carrying out.

0:57:40.160 --> 0:57:44.040
<v Speaker 1>Nune published what would be his last paper, Prophylactic Inoculation

0:57:44.120 --> 0:57:47.720
<v Speaker 1>against hay Fever, in nineteen eleven, and he died two

0:57:47.800 --> 0:57:51.800
<v Speaker 1>years later at the age of thirty five. Ah, that's tuberculosis,

0:57:51.880 --> 0:57:55.560
<v Speaker 1>Yeah it is. Freeman continued this work for the next

0:57:55.600 --> 0:57:59.360
<v Speaker 1>few years and showed that using this immunotherapy approach, in

0:57:59.480 --> 0:58:04.160
<v Speaker 1>thirty per of participants, hay fever was effectively cured.

0:58:04.520 --> 0:58:04.960
<v Speaker 4>Wow.

0:58:05.120 --> 0:58:08.960
<v Speaker 1>In thirty five percent, symptoms were greatly improved in twenty

0:58:08.960 --> 0:58:12.520
<v Speaker 1>four percent slightly improved, and only twelve percent had no

0:58:12.680 --> 0:58:18.320
<v Speaker 1>improvements whatsoever. Wow, it's pretty impressive. Yeah, noon, and Freeman's

0:58:18.320 --> 0:58:21.960
<v Speaker 1>work was truly foundational for the field of immunotherapy. Not

0:58:22.040 --> 0:58:25.960
<v Speaker 1>only did it demonstrate that long term improvement was possible

0:58:26.000 --> 0:58:28.960
<v Speaker 1>for at least one type of allergy, it also provided

0:58:29.000 --> 0:58:32.640
<v Speaker 1>a roadmap for healthcare practitioners to try this out on

0:58:32.760 --> 0:58:36.600
<v Speaker 1>their patients, and for researchers to tweak the protocol, testing

0:58:36.680 --> 0:58:40.040
<v Speaker 1>it out with other allergens, developing a combo shot, improving

0:58:40.120 --> 0:58:43.840
<v Speaker 1>safety standardization, and so on. And I'm not going to

0:58:43.880 --> 0:58:47.560
<v Speaker 1>go into those later improvements. Instead, I wanted to focus

0:58:47.640 --> 0:58:51.240
<v Speaker 1>on these early years because I want us to consider

0:58:51.320 --> 0:58:56.600
<v Speaker 1>the timing. The time from description, identification of cause, and

0:58:56.760 --> 0:59:01.680
<v Speaker 1>effective treatment happened lightning fast for hay fever in science years.

0:59:02.520 --> 0:59:04.640
<v Speaker 1>But if we placed it in the context of what

0:59:04.760 --> 0:59:07.400
<v Speaker 1>else was happening in the science world at the time,

0:59:07.800 --> 0:59:12.480
<v Speaker 1>it's clear to see why, or at least partially why. Vaccines.

0:59:13.600 --> 0:59:16.760
<v Speaker 1>Although the smallpox vaccine had been around since the late

0:59:16.800 --> 0:59:20.120
<v Speaker 1>eighteen hundreds, no other vaccines were developed until the end

0:59:20.200 --> 0:59:24.080
<v Speaker 1>of the nineteenth century. Around the eighteen seventies, and eighteen eighties,

0:59:24.240 --> 0:59:27.640
<v Speaker 1>which is right when Blackley's work on hay fever came out,

0:59:28.440 --> 0:59:31.640
<v Speaker 1>and with the growing number of vaccine success stories and

0:59:31.680 --> 0:59:35.680
<v Speaker 1>the development of anti tooxin, everyone with a remote interest

0:59:35.760 --> 0:59:39.920
<v Speaker 1>in microbiology or immunology began trying their hand at developing

0:59:39.920 --> 0:59:43.800
<v Speaker 1>a vaccine and using the germ theory framework to describe

0:59:43.800 --> 0:59:47.960
<v Speaker 1>what happens with an allergen exposure. Along with the concepts

0:59:48.000 --> 0:59:53.680
<v Speaker 1>of immunity, immunization, susceptibility, toxin, antiitoxin, and so on, it

0:59:53.720 --> 0:59:58.680
<v Speaker 1>seemed entirely reasonable that if vaccines worked for pathogens introduced

0:59:58.680 --> 1:00:01.280
<v Speaker 1>a little bit to prevent someone from getting sick in

1:00:01.280 --> 1:00:05.120
<v Speaker 1>the future, then maybe that could work for allergens. Voila

1:00:05.320 --> 1:00:09.160
<v Speaker 1>allergy shots. Yeah, so in a sense, we have vaccines

1:00:09.200 --> 1:00:09.520
<v Speaker 1>to think.

1:00:10.080 --> 1:00:13.000
<v Speaker 4>That is so interesting, Arin, I really love that.

1:00:14.880 --> 1:00:17.000
<v Speaker 1>I just can't believe how old it is, Like it

1:00:17.080 --> 1:00:22.240
<v Speaker 1>makes sense, but it's also like I just can't believe it.

1:00:22.240 --> 1:00:23.160
<v Speaker 1>It's also just like.

1:00:23.320 --> 1:00:28.440
<v Speaker 4>So so so interesting immunologically that it works and that

1:00:28.520 --> 1:00:30.640
<v Speaker 4>it works the way that it does, and like it

1:00:30.240 --> 1:00:33.960
<v Speaker 4>just it makes me have so many more questions about

1:00:34.240 --> 1:00:38.440
<v Speaker 4>our immune response and like tolerance versus resistance, you know

1:00:38.440 --> 1:00:38.880
<v Speaker 4>what I mean?

1:00:39.080 --> 1:00:42.360
<v Speaker 1>Oh, tolerance versus resistance is such a fascinating question.

1:00:42.600 --> 1:00:46.040
<v Speaker 4>It really is, and it's like, oh.

1:00:45.600 --> 1:00:48.600
<v Speaker 1>Yeah, yeah, And it doesn't work like vaccines in a

1:00:48.600 --> 1:00:52.200
<v Speaker 1>way either, right, like vaccines sensitize you to see exactly.

1:00:52.680 --> 1:00:56.400
<v Speaker 4>It is like the opposite of vaccines. Yeah, but also

1:00:56.520 --> 1:00:58.640
<v Speaker 4>the same as vaccines, right, because it is it is

1:00:58.760 --> 1:01:02.800
<v Speaker 4>shifting your immune RESCE response to be an IgG response,

1:01:02.840 --> 1:01:05.520
<v Speaker 4>which is what we see with vaccines. But they a

1:01:05.760 --> 1:01:09.200
<v Speaker 4>didn't know that, of course, and B like it is

1:01:09.320 --> 1:01:12.840
<v Speaker 4>because you already had an abnormal Well is it abnormal?

1:01:12.880 --> 1:01:15.320
<v Speaker 4>We don't know, but you had this IgE response and

1:01:15.320 --> 1:01:17.240
<v Speaker 4>you're having to shift it. So it is it is

1:01:17.360 --> 1:01:22.520
<v Speaker 4>tolerance rather than this like prime rebility to resist in

1:01:22.560 --> 1:01:26.640
<v Speaker 4>the future. What I know, it is so weird.

1:01:27.040 --> 1:01:29.040
<v Speaker 1>It's weird, and I love it.

1:01:29.280 --> 1:01:31.520
<v Speaker 4>I love it. I love it.

1:01:31.760 --> 1:01:34.240
<v Speaker 1>Are you ready for our next chapter? I really am

1:01:34.400 --> 1:01:41.520
<v Speaker 1>okay chapter two? Thank you. Pharmacology. Just as allergy shots

1:01:41.520 --> 1:01:45.080
<v Speaker 1>were a product of their time and the excitement surrounding vaccines,

1:01:45.560 --> 1:01:48.520
<v Speaker 1>any histamines came out of an era that saw the

1:01:48.560 --> 1:01:53.040
<v Speaker 1>birth of modern pharmacology. By the mid to late eighteen hundreds,

1:01:53.080 --> 1:01:57.400
<v Speaker 1>the fields of chemistry and biochemistry had made huge technological

1:01:57.440 --> 1:02:01.600
<v Speaker 1>advancements that allowed scientists to isolate and refine more and

1:02:01.720 --> 1:02:06.680
<v Speaker 1>more compounds, especially those from living organisms. The goal of

1:02:06.720 --> 1:02:10.840
<v Speaker 1>this work was basically to understand how stuff works, link

1:02:10.880 --> 1:02:14.520
<v Speaker 1>a compound to its function. Then if a certain compound

1:02:14.560 --> 1:02:19.280
<v Speaker 1>did something interesting or helpful, like quinine treating malaria, you

1:02:19.320 --> 1:02:22.600
<v Speaker 1>could take steps to either isolate larger quantities of it

1:02:22.720 --> 1:02:26.960
<v Speaker 1>from natural sources or try your hand at producing it Artificially,

1:02:27.800 --> 1:02:31.200
<v Speaker 1>it sounds like a straightforward process, but in reality this

1:02:31.280 --> 1:02:35.720
<v Speaker 1>type of work often led researchers down unexpected roads, which

1:02:35.760 --> 1:02:39.400
<v Speaker 1>is exactly what happened for Henry Dale and George Barker.

1:02:39.800 --> 1:02:40.080
<v Speaker 4>Okay.

1:02:40.400 --> 1:02:43.600
<v Speaker 1>Dale and Barker were working at Sir Henry Welcome's research

1:02:43.680 --> 1:02:47.800
<v Speaker 1>lab in England of Welcome Collection Welcome Library. When they

1:02:47.800 --> 1:02:51.240
<v Speaker 1>turned their sites to ergit. Welcome became interested in the

1:02:51.240 --> 1:02:54.640
<v Speaker 1>commercial potential of ergot as a medication to speed up

1:02:54.720 --> 1:02:59.160
<v Speaker 1>labor during childbirth and reduce postpartum bleeding, both of which

1:02:59.320 --> 1:03:02.880
<v Speaker 1>ergot had been shown to do. But no one really understood.

1:03:02.400 --> 1:03:06.240
<v Speaker 4>How I love this. We talked about er way.

1:03:06.000 --> 1:03:09.600
<v Speaker 1>Back in a dancing plague. Dancing plague, that's right, we

1:03:09.640 --> 1:03:13.480
<v Speaker 1>should do just an ergic episode, really Okay.

1:03:16.560 --> 1:03:18.600
<v Speaker 4>I mean we say, like we could make anything into

1:03:18.640 --> 1:03:20.160
<v Speaker 4>an episode, so like, I don't know.

1:03:20.520 --> 1:03:23.240
<v Speaker 1>I mean, this could have been three additional episodes. Let's like,

1:03:23.360 --> 1:03:28.280
<v Speaker 1>let's be real. But ergo on its own is not

1:03:28.440 --> 1:03:31.040
<v Speaker 1>something you really want to mess with, and so the

1:03:31.120 --> 1:03:35.160
<v Speaker 1>key was to find the compound that had these desired effects,

1:03:35.600 --> 1:03:38.320
<v Speaker 1>isolate it, and then turn it into a medication with

1:03:38.440 --> 1:03:43.480
<v Speaker 1>fewer side effects than straight up ergo. So Dale, Barger

1:03:43.520 --> 1:03:47.600
<v Speaker 1>and another researcher, laid Law, began this process of isolating

1:03:47.680 --> 1:03:52.240
<v Speaker 1>various compounds from ergo and then injecting them into various animals.

1:03:52.880 --> 1:03:56.840
<v Speaker 1>One compound in particular caught their eye. Beta. I'm gonna

1:03:56.840 --> 1:04:01.160
<v Speaker 1>try to say this Beta Emma dazzle eel, folamine, or

1:04:01.200 --> 1:04:04.040
<v Speaker 1>as we know it, histamine. Okay, so glad I don't

1:04:04.040 --> 1:04:09.520
<v Speaker 1>have to say that again. It was brutal. Histamine had

1:04:09.560 --> 1:04:13.000
<v Speaker 1>been isolated previously, but Dale and laid Law were the

1:04:13.000 --> 1:04:16.600
<v Speaker 1>first to look into what it actually did, and what

1:04:16.640 --> 1:04:20.040
<v Speaker 1>they found was pretty compelling. It caused all the things

1:04:20.080 --> 1:04:24.160
<v Speaker 1>you talked about aaron phasodilation, the contraction of smooth muscles

1:04:24.200 --> 1:04:27.320
<v Speaker 1>in the airways, in the uterus, in the intestines. It

1:04:27.400 --> 1:04:32.800
<v Speaker 1>increased heart rate and stimulated contraction. Overall, injection with histamine

1:04:32.880 --> 1:04:36.000
<v Speaker 1>induced a response in animals that looked a whole lot

1:04:36.080 --> 1:04:39.840
<v Speaker 1>like anaphylactic shock, which they pointed out at the very

1:04:39.960 --> 1:04:43.600
<v Speaker 1>end of their nineteen ten paper as a possible avenue

1:04:43.680 --> 1:04:44.760
<v Speaker 1>for future research.

1:04:45.480 --> 1:04:48.800
<v Speaker 4>Wow. Nineteen ten, nineteen ten.

1:04:49.040 --> 1:04:52.720
<v Speaker 1>I know anaphylaxis, by the way, had only been described

1:04:52.760 --> 1:04:55.800
<v Speaker 1>eight years prior in nineteen oh two, which is pretty

1:04:55.800 --> 1:05:00.200
<v Speaker 1>early by Rochet and Portier. Dale and Laidlaw's paper went

1:05:00.280 --> 1:05:05.320
<v Speaker 1>a long way towards linking histamine and allergy slash anaphylaxis,

1:05:05.520 --> 1:05:10.120
<v Speaker 1>but the connection wasn't quite complete. This compound from ergo

1:05:10.280 --> 1:05:14.560
<v Speaker 1>can cause this reaction, but does it have biological significance?

1:05:14.640 --> 1:05:14.760
<v Speaker 3>Like?

1:05:14.840 --> 1:05:18.840
<v Speaker 1>Is this something that animals regularly encounter? The answer to

1:05:18.880 --> 1:05:22.720
<v Speaker 1>that would arrive in nineteen twenty seven, when Charles Best

1:05:23.000 --> 1:05:26.480
<v Speaker 1>of insulin fame. He was one of the people who yep,

1:05:27.560 --> 1:05:32.080
<v Speaker 1>he isolated histamine from liver and lungs, showing that this

1:05:32.200 --> 1:05:35.840
<v Speaker 1>compound is produced regularly in animal tissue and that it

1:05:35.840 --> 1:05:39.360
<v Speaker 1>plays a strong role in allergy and anaphylaxis.

1:05:39.680 --> 1:05:42.120
<v Speaker 4>This is so fun, Eric, I can't tell you how

1:05:42.200 --> 1:05:44.400
<v Speaker 4>much I love learning this stuff that I've never learned

1:05:44.400 --> 1:05:47.400
<v Speaker 4>about like where we got anahistamines from.

1:05:47.760 --> 1:05:50.240
<v Speaker 1>I know, I just also I love I think it's

1:05:50.280 --> 1:05:53.680
<v Speaker 1>so fascinating to read about that period of science where

1:05:53.680 --> 1:05:56.680
<v Speaker 1>it was just sort of like throwing a dart and

1:05:56.720 --> 1:06:00.400
<v Speaker 1>being like cool, let's check out this compound. Yeah, and

1:06:00.440 --> 1:06:03.800
<v Speaker 1>it does this thing. Let's look at this microbe. It's

1:06:03.840 --> 1:06:09.400
<v Speaker 1>just everything. Yeah. Yeah, open questions so many. Once this

1:06:09.520 --> 1:06:13.720
<v Speaker 1>link was made between animals produce histamine on the rag

1:06:14.040 --> 1:06:16.840
<v Speaker 1>and it seems to be linked to allergy and anaphylaxis

1:06:16.880 --> 1:06:19.760
<v Speaker 1>in some way, then the logic followed that if you

1:06:19.760 --> 1:06:23.200
<v Speaker 1>could find a way to block the action of histamine,

1:06:23.760 --> 1:06:27.560
<v Speaker 1>you could reduce those unpleasant and deadly effects that it caused.

1:06:28.200 --> 1:06:30.440
<v Speaker 1>But how do you do that? Yeah, you look for

1:06:30.560 --> 1:06:35.440
<v Speaker 1>compounds that bind to histamine receptors, blocking histamine from binding.

1:06:35.920 --> 1:06:37.800
<v Speaker 4>I mean, straightforward when you say it like.

1:06:37.760 --> 1:06:41.920
<v Speaker 1>That, straightforward, right, easy enough? I mean, but in a way,

1:06:42.560 --> 1:06:46.360
<v Speaker 1>it was only ten years after Best isolated histamine from

1:06:46.400 --> 1:06:50.360
<v Speaker 1>animal tissues that the first antihistamines emerged. So it was

1:06:50.440 --> 1:06:54.760
<v Speaker 1>nineteen thirty seven is when Daniel Beauvet, who identified the

1:06:54.760 --> 1:06:58.160
<v Speaker 1>first antihistamine and then was later awarded a Nobel Prize

1:06:58.160 --> 1:07:00.600
<v Speaker 1>for his efforts. Nineteen thirty seven is one that happened.

1:07:01.040 --> 1:07:01.640
<v Speaker 4>Wow.

1:07:01.800 --> 1:07:04.440
<v Speaker 1>And they were on the market by the mid nineteen forties.

1:07:05.720 --> 1:07:13.320
<v Speaker 4>Wow, I know that's so much earlier. Same today, I

1:07:13.360 --> 1:07:16.240
<v Speaker 4>think of the nineteen fifties, it's like medicines didn't exist,

1:07:17.600 --> 1:07:19.920
<v Speaker 4>which I know I had antibiotics.

1:07:20.000 --> 1:07:25.240
<v Speaker 1>Yeah that's true. But yeah, that first antihistamy I feel

1:07:25.280 --> 1:07:28.600
<v Speaker 1>like Benaedrux was nineteen forty six something like that. Wow.

1:07:29.080 --> 1:07:30.640
<v Speaker 4>Yeah, that is so cool.

1:07:31.120 --> 1:07:33.640
<v Speaker 1>And again, these are the first generation, right. I could

1:07:33.680 --> 1:07:36.840
<v Speaker 1>tell a whole separate story about the research that followed

1:07:37.160 --> 1:07:40.880
<v Speaker 1>from this first generation of antaistamines. You know, how we

1:07:41.000 --> 1:07:44.440
<v Speaker 1>discovered the second generation histamines, all the different receptors, the

1:07:44.520 --> 1:07:47.360
<v Speaker 1>recognition that they could help with things like motion sickness,

1:07:47.800 --> 1:07:52.320
<v Speaker 1>the discovery that some antihistamines could have potentially harmful cardiac

1:07:52.400 --> 1:07:56.040
<v Speaker 1>side effects, the identification of their sedative effect. I mean,

1:07:56.080 --> 1:08:01.160
<v Speaker 1>there's a lot more to the history of antihistamines. I

1:08:01.160 --> 1:08:05.080
<v Speaker 1>would read that book erin Well, I'll have to save

1:08:05.160 --> 1:08:08.160
<v Speaker 1>that story for another day because we've still got the

1:08:08.280 --> 1:08:11.160
<v Speaker 1>last of the big three allergy treatments to get into,

1:08:11.440 --> 1:08:16.200
<v Speaker 1>and that is the epinephrine autoinjector SLASH the EpiPen, love

1:08:16.240 --> 1:08:24.160
<v Speaker 1>it chapter three, Thank you Sheldon, Sheldon Sheldon. The EpiPen

1:08:24.400 --> 1:08:28.320
<v Speaker 1>is one of the most powerful medical devices you hope

1:08:28.320 --> 1:08:32.280
<v Speaker 1>you never have to use. It has saved countless lives

1:08:32.280 --> 1:08:36.799
<v Speaker 1>from anaphylaxis since its initial introduction, and millions of people

1:08:36.880 --> 1:08:40.400
<v Speaker 1>around the world rely on EpiPens to save their lives

1:08:40.439 --> 1:08:45.080
<v Speaker 1>from severe allergic reactions. We owe the existence of this

1:08:45.280 --> 1:08:50.960
<v Speaker 1>amazing device to two separate but equally crucial developments in medicine,

1:08:51.120 --> 1:08:55.200
<v Speaker 1>the discovery of adrenaline slash epinephrine and the invention of

1:08:55.280 --> 1:08:59.920
<v Speaker 1>the autoinjector. Let's begin with adrenaline again, placing ourselves in

1:09:00.120 --> 1:09:04.280
<v Speaker 1>the late eighteen hundreds, when, alongside the fields of vaccinology

1:09:04.360 --> 1:09:08.240
<v Speaker 1>and pharmacology, the study of hormones was also kicking off.

1:09:09.320 --> 1:09:13.840
<v Speaker 1>Two researchers, George Oliver and Ea Shaeffer, ground up a

1:09:13.880 --> 1:09:17.559
<v Speaker 1>bunch of adrenal glands from various animals, swirled them up

1:09:17.560 --> 1:09:20.759
<v Speaker 1>with some alcohol and glycerine, and injected it into dogs

1:09:20.920 --> 1:09:22.080
<v Speaker 1>just to see what would happen.

1:09:24.760 --> 1:09:25.800
<v Speaker 4>Oh my goodness.

1:09:25.960 --> 1:09:29.960
<v Speaker 1>Okay, yeah, not great. This idea didn't come out of

1:09:30.080 --> 1:09:33.479
<v Speaker 1>thin air, though several other researchers had attempted something similar,

1:09:33.680 --> 1:09:38.400
<v Speaker 1>but no one had thoroughly characterized a typical response. Usually

1:09:38.479 --> 1:09:41.880
<v Speaker 1>it was just death, yeah, because it was like not

1:09:42.240 --> 1:09:45.400
<v Speaker 1>very purified, right, hormone.

1:09:44.760 --> 1:09:47.080
<v Speaker 4>Extra, lots of ways that that could kill a dog.

1:09:47.200 --> 1:09:51.920
<v Speaker 1>Just yeah, yeah, yeah absolutely. Oliver and Schaeffer were the

1:09:51.960 --> 1:09:55.200
<v Speaker 1>first to actually say, Okay, this is what happens. They

1:09:55.280 --> 1:09:58.880
<v Speaker 1>noted that the dogs receiving the adrenal gland extract had

1:09:58.960 --> 1:10:03.720
<v Speaker 1>elevated heart rate, vasodilation, increased blood pressure, and reduced respiratory rate.

1:10:04.320 --> 1:10:07.559
<v Speaker 1>It's kind of a messy suite of symptoms. Yes, it's

1:10:07.600 --> 1:10:08.120
<v Speaker 1>not messy.

1:10:08.320 --> 1:10:09.920
<v Speaker 4>Adrenal glands are messy.

1:10:10.280 --> 1:10:12.599
<v Speaker 1>Yeah, there's a lot of stuff going on there.

1:10:12.640 --> 1:10:15.000
<v Speaker 4>They make a lot more than just adrenaline.

1:10:15.160 --> 1:10:19.800
<v Speaker 1>Yeah, inducing this type of response, they recognized could come

1:10:19.800 --> 1:10:22.960
<v Speaker 1>in handy, But first you needed to find out exactly

1:10:23.040 --> 1:10:26.280
<v Speaker 1>what was triggering this response or the different parts of

1:10:26.320 --> 1:10:31.080
<v Speaker 1>this response. Several researchers set to isolating the responsible compound,

1:10:31.560 --> 1:10:36.040
<v Speaker 1>and in nineteen oh one, Jokichi Takamine would ultimately claim

1:10:36.080 --> 1:10:40.880
<v Speaker 1>the title calling the substance adrenaline, which Park Davison Company,

1:10:40.960 --> 1:10:44.719
<v Speaker 1>later owned by Pfizer, patented in nineteen oh three. What

1:10:45.800 --> 1:10:48.120
<v Speaker 1>I don't know that, yeah, yeah.

1:10:48.040 --> 1:10:50.240
<v Speaker 4>So that's why we call it up enprind because.

1:10:50.120 --> 1:10:55.120
<v Speaker 1>A trade name. Yeah. Once people were able to synthetically

1:10:55.160 --> 1:10:59.400
<v Speaker 1>produce adrenaline in nineteen oh six, it quickly became one

1:10:59.439 --> 1:11:02.839
<v Speaker 1>of the most studied hormones over the first few decades

1:11:02.840 --> 1:11:06.599
<v Speaker 1>of the twentieth century, as researchers sought to identify possible

1:11:06.640 --> 1:11:11.960
<v Speaker 1>therapeutic targets among those asthma and hay fever. Since at

1:11:12.080 --> 1:11:16.600
<v Speaker 1>least eighteen fifty nine, physicians had observed that quote asthma

1:11:16.640 --> 1:11:20.360
<v Speaker 1>is immediately cured in situations of either sudden alarm or

1:11:20.479 --> 1:11:22.800
<v Speaker 1>violent fleeting excitements.

1:11:23.760 --> 1:11:26.439
<v Speaker 4>When you're activating the sympathetic nervous system eric.

1:11:26.520 --> 1:11:29.760
<v Speaker 1>Uh huh, And so researchers figured, look, here's this thing,

1:11:29.800 --> 1:11:33.800
<v Speaker 1>adrenaline that causes the same sensations as sudden alarm or

1:11:33.920 --> 1:11:38.679
<v Speaker 1>violent fleeting excitements. Maybe we injected into people with asthma

1:11:38.720 --> 1:11:41.920
<v Speaker 1>and hay fever and just see what happens. And in

1:11:41.960 --> 1:11:44.960
<v Speaker 1>the first few years of the nineteen hundreds, that's exactly

1:11:45.000 --> 1:11:49.320
<v Speaker 1>what Solomon solis Cohen, Jesse Bulowa, and David Kaplan did,

1:11:49.840 --> 1:11:53.839
<v Speaker 1>finding that both oral and injected doses of adrenaline relieved

1:11:53.880 --> 1:11:58.519
<v Speaker 1>symptoms of both conditions, but a major question remained, well,

1:11:58.760 --> 1:12:02.000
<v Speaker 1>I mean several major quests remained, like what is adrenaline

1:12:02.040 --> 1:12:04.680
<v Speaker 1>doing at a cellular level? But for the purposes of

1:12:04.680 --> 1:12:08.880
<v Speaker 1>this history, the main unanswered question was what is the

1:12:08.920 --> 1:12:13.759
<v Speaker 1>best way to get adrenaline into someone? As a treatment

1:12:13.800 --> 1:12:16.680
<v Speaker 1>for hay fever and asthma. You really had to get

1:12:16.720 --> 1:12:19.839
<v Speaker 1>adrenaline into someone as fast as possible to be effective,

1:12:20.280 --> 1:12:25.720
<v Speaker 1>which meant injection, specifically intramuscular injection, over oral tablet or

1:12:25.800 --> 1:12:29.320
<v Speaker 1>other kinds of injections. But how many people are lucky

1:12:29.439 --> 1:12:32.280
<v Speaker 1>enough to have a syringe and vial of adrenaline on

1:12:32.479 --> 1:12:35.240
<v Speaker 1>hand during an attack? And even if you are like

1:12:35.400 --> 1:12:38.040
<v Speaker 1>drawing up the liquid into the needle while your throat

1:12:38.120 --> 1:12:43.120
<v Speaker 1>is constricting not an ideal delivery system, especially when, as

1:12:43.160 --> 1:12:47.799
<v Speaker 1>we talked about, every second counts. By the nineteen thirties,

1:12:48.040 --> 1:12:52.000
<v Speaker 1>researchers had developed nebulizers, which helped to solve the problem

1:12:52.000 --> 1:12:56.120
<v Speaker 1>for people with asthma, but getting adrenaline into someone going

1:12:56.160 --> 1:13:01.679
<v Speaker 1>into anaphylaxis was still a huge challenge. Fortunately, a solution

1:13:01.880 --> 1:13:06.000
<v Speaker 1>was on the horizon, but it wasn't initially created with

1:13:06.160 --> 1:13:11.200
<v Speaker 1>adrenaline in mind. During the Cold War, a big fear

1:13:11.880 --> 1:13:15.719
<v Speaker 1>was that troops would encounter nerve gas which acted rapidly

1:13:15.840 --> 1:13:19.000
<v Speaker 1>to incapacitat or kill like nerve gas would be within seconds, right,

1:13:19.520 --> 1:13:23.240
<v Speaker 1>and so the military was understandably very motivated to find

1:13:23.240 --> 1:13:26.680
<v Speaker 1>a way to deliver an antidote as quickly as possible.

1:13:27.000 --> 1:13:29.000
<v Speaker 4>Oh my gosh, Aaron.

1:13:29.320 --> 1:13:35.600
<v Speaker 1>I know. Sheldon Kaplan an engineer working at Survival Technology Incorporated.

1:13:35.880 --> 1:13:37.040
<v Speaker 1>What a name for?

1:13:37.240 --> 1:13:37.880
<v Speaker 3>What a name?

1:13:38.200 --> 1:13:38.400
<v Speaker 1>Right?

1:13:38.920 --> 1:13:41.280
<v Speaker 4>Survival Technology? Does it still exist?

1:13:44.200 --> 1:13:47.920
<v Speaker 1>But Sheldon had just the thing. One of his projects

1:13:47.960 --> 1:13:51.960
<v Speaker 1>at the company was redesigning the astropen, which was an

1:13:51.960 --> 1:13:55.759
<v Speaker 1>autoinjector that had limited usefulness since it used stainless steel

1:13:55.840 --> 1:13:58.519
<v Speaker 1>to hold the medication rather than glass, which was thought

1:13:58.560 --> 1:14:00.400
<v Speaker 1>to be too fragile. And I think, I think that

1:14:00.479 --> 1:14:04.320
<v Speaker 1>this was developed with astronauts in mind. But again, you

1:14:04.360 --> 1:14:07.920
<v Speaker 1>could only do certain medications because some medications when they

1:14:08.160 --> 1:14:10.240
<v Speaker 1>come into contact with stainless steel, not a good thing.

1:14:10.240 --> 1:14:10.679
<v Speaker 3>Interact.

1:14:11.000 --> 1:14:17.080
<v Speaker 1>Yeah, okay, But this problem didn't stop Sheldon. He rebuilt

1:14:17.080 --> 1:14:21.600
<v Speaker 1>the pen entirely using glass and developing a system to

1:14:21.760 --> 1:14:26.360
<v Speaker 1>carefully calibrate the dose. Sheldon's new pen was called the

1:14:26.400 --> 1:14:29.360
<v Speaker 1>combo pen, and this is what the military used to

1:14:29.439 --> 1:14:31.519
<v Speaker 1>deliver antidotes to nerve gas.

1:14:31.800 --> 1:14:32.360
<v Speaker 4>Wow.

1:14:32.600 --> 1:14:36.000
<v Speaker 1>But Sheldon saw the great potential that this pen had

1:14:36.080 --> 1:14:40.160
<v Speaker 1>outside of the military for the general population. He reworked

1:14:40.160 --> 1:14:46.320
<v Speaker 1>it to contain adrenaline epinephrine, and the world's first epinephrine autoinjector,

1:14:46.640 --> 1:14:50.800
<v Speaker 1>developed in nineteen seventy six, was officially approved by the

1:14:50.840 --> 1:14:53.840
<v Speaker 1>FDA to treat anaphylaxis in nineteen eighty seven.

1:14:55.000 --> 1:14:55.880
<v Speaker 4>Wow.

1:14:56.400 --> 1:15:00.720
<v Speaker 1>I know he had the vision right. He saw this

1:15:00.800 --> 1:15:03.160
<v Speaker 1>and was like, there's so much more that we can

1:15:03.200 --> 1:15:08.400
<v Speaker 1>do with this. Wow. Yeah. The EpiPen would go on

1:15:08.560 --> 1:15:12.920
<v Speaker 1>to become a household name and make pharmaceutical companies billions

1:15:12.960 --> 1:15:16.640
<v Speaker 1>of dollars, thanks especially to price gouging. Yet again, but

1:15:16.760 --> 1:15:20.599
<v Speaker 1>Sheldon Caplin never received any money for his invention, even

1:15:20.640 --> 1:15:22.720
<v Speaker 1>though his name is on the patent. And I bet

1:15:22.720 --> 1:15:25.479
<v Speaker 1>that most people have never heard of this incredible inventor

1:15:25.720 --> 1:15:30.479
<v Speaker 1>whose work and brilliance has saved untold lives. Oh wow,

1:15:30.760 --> 1:15:32.599
<v Speaker 1>So let's give it up to Sheldon.

1:15:32.640 --> 1:15:36.320
<v Speaker 4>Kaplay gave it up for Sheldon, Oh my goodness.

1:15:36.600 --> 1:15:39.600
<v Speaker 1>And there have been so many interesting developments and like

1:15:39.640 --> 1:15:42.639
<v Speaker 1>you talked about different delivery systems like a box versus

1:15:42.840 --> 1:15:45.160
<v Speaker 1>n you know, and there have been studies looking at well,

1:15:45.160 --> 1:15:47.479
<v Speaker 1>if you conceal the needle, it makes people more likely

1:15:47.520 --> 1:15:49.160
<v Speaker 1>to use it because it's less scary.

1:15:49.680 --> 1:15:52.519
<v Speaker 4>Also, I am sure, and like I don't know enough

1:15:52.520 --> 1:15:54.760
<v Speaker 4>about the history of development of other medications, but like

1:15:54.840 --> 1:16:00.400
<v Speaker 4>we use similar types of delivery systems for so many medications. Now,

1:16:00.439 --> 1:16:03.680
<v Speaker 4>It's not just epinephrine, right, yeah, even all of the

1:16:03.800 --> 1:16:08.559
<v Speaker 4>ozempics of the world. The tide is the non brand name, right,

1:16:08.640 --> 1:16:11.640
<v Speaker 4>Like all of these kinds of medications, insulin pens, like

1:16:11.720 --> 1:16:14.639
<v Speaker 4>all of these things that have the ability to deliver

1:16:14.720 --> 1:16:18.120
<v Speaker 4>a fixed dose amount in a way where you in

1:16:18.160 --> 1:16:21.519
<v Speaker 4>a lot of cases have very minimal contact with the needle.

1:16:21.600 --> 1:16:24.639
<v Speaker 4>Part of It's wow, that is so interesting, Arin.

1:16:25.080 --> 1:16:30.000
<v Speaker 1>Yeah, so all from cold war nerve Gas, the genius

1:16:30.000 --> 1:16:32.800
<v Speaker 1>of Sheldon Kaplan. I love it.

1:16:32.840 --> 1:16:33.759
<v Speaker 4>How fun Aaron?

1:16:34.080 --> 1:16:34.360
<v Speaker 1>Yeah.

1:16:34.400 --> 1:16:37.080
<v Speaker 4>Also nineteen eighty seven. I don't know if that feels

1:16:37.080 --> 1:16:40.000
<v Speaker 4>earlier late. I don't know, but I love to know

1:16:40.040 --> 1:16:40.439
<v Speaker 4>that date.

1:16:40.920 --> 1:16:42.920
<v Speaker 1>Yeah, I don't know how I feel about it. I'll

1:16:42.920 --> 1:16:43.599
<v Speaker 1>search my soul.

1:16:44.080 --> 1:16:44.639
<v Speaker 4>Yeah, same.

1:16:44.720 --> 1:16:49.840
<v Speaker 1>Yeah. Well, well, Aarin, that was a quick tour through

1:16:49.880 --> 1:16:52.600
<v Speaker 1>the histories of some allergy treatments, and I know that

1:16:52.640 --> 1:16:55.480
<v Speaker 1>we've got a lot of interesting potential on the horizon.

1:16:55.960 --> 1:16:57.559
<v Speaker 1>And so I'm going to turn it over to you

1:16:57.640 --> 1:17:00.559
<v Speaker 1>to let us know where we might be going allergy

1:17:00.600 --> 1:17:01.599
<v Speaker 1>treatments today.

1:17:02.000 --> 1:17:41.120
<v Speaker 4>I'll do that right after this break. So we talked already, Aaron,

1:17:41.320 --> 1:17:46.320
<v Speaker 4>because you asked, like, well, allergy shots, food allergies, what's up? Okay, Well,

1:17:48.120 --> 1:17:53.280
<v Speaker 4>let me tell you there is a very new and

1:17:53.360 --> 1:17:55.040
<v Speaker 4>by very new, I mean it was approved in the

1:17:55.160 --> 1:18:01.960
<v Speaker 4>US in twenty twenty, oral immunotherapy OI as opposed to

1:18:02.160 --> 1:18:07.080
<v Speaker 4>scit or slit for subcutaneous or sublingual. This is oral

1:18:07.200 --> 1:18:14.040
<v Speaker 4>in your mouth imminotherapy for peanut allergy. It exists arin Yes, nice.

1:18:14.280 --> 1:18:18.120
<v Speaker 4>Peanut allergy affects in the US one point two percent

1:18:18.160 --> 1:18:20.559
<v Speaker 4>of the entire population and two and a half percent

1:18:20.600 --> 1:18:26.000
<v Speaker 4>of kids. And peanut allergy specifically is associated with like

1:18:26.040 --> 1:18:29.760
<v Speaker 4>a disproportionate amount of anaphylaxis cases that end up in

1:18:29.760 --> 1:18:33.160
<v Speaker 4>the emergency room. So that is why peanut allergy has

1:18:33.200 --> 1:18:36.200
<v Speaker 4>been the one that people have been studying to try

1:18:36.200 --> 1:18:39.799
<v Speaker 4>and come up with treatment for. So this new treatment

1:18:39.840 --> 1:18:42.200
<v Speaker 4>that exists, I didn't even write down the brand name

1:18:42.240 --> 1:18:44.519
<v Speaker 4>because I didn't and now I forget. But it's a

1:18:44.560 --> 1:18:47.320
<v Speaker 4>powder and it's made from peanuts, like it's just made

1:18:47.320 --> 1:18:51.960
<v Speaker 4>from peanut protein erin, but it's used as oral immunotherapy

1:18:52.080 --> 1:18:55.800
<v Speaker 4>in a very similar type of desensitization therapy. And the

1:18:55.880 --> 1:19:00.040
<v Speaker 4>difference between this and just feeding a kid peanuts to

1:19:00.120 --> 1:19:04.160
<v Speaker 4>try and desensitize them are a few things. One, it's

1:19:04.200 --> 1:19:08.439
<v Speaker 4>been very well studied to be safe and well tolerated. Two,

1:19:08.560 --> 1:19:12.040
<v Speaker 4>it is made to have a very specific and predictable

1:19:12.320 --> 1:19:16.519
<v Speaker 4>level of allergen exposure, right. That is why it is

1:19:16.640 --> 1:19:19.840
<v Speaker 4>approved and safer than just trying to eat peanuts to

1:19:19.880 --> 1:19:27.600
<v Speaker 4>desensitize yourself. And the therapy regimen itself seems pretty complex.

1:19:28.280 --> 1:19:32.760
<v Speaker 4>It is multiple exposures per day. It is daily exposure.

1:19:32.840 --> 1:19:35.920
<v Speaker 4>It's not like subcutaneous immunotherapy where you just go like

1:19:36.000 --> 1:19:39.759
<v Speaker 4>weekly exposures or something like that. And so it often

1:19:39.920 --> 1:19:43.120
<v Speaker 4>starts in an allergist office or in your physician's office

1:19:43.160 --> 1:19:47.160
<v Speaker 4>with these monitored, very well controlled exposures, and then has

1:19:47.200 --> 1:19:49.920
<v Speaker 4>to continue at home where you're doing this every single day,

1:19:50.160 --> 1:19:52.640
<v Speaker 4>often multiple times a day. And then every time that

1:19:52.720 --> 1:19:56.759
<v Speaker 4>you increase the dose, which happens slowly over weeks to months,

1:19:57.320 --> 1:19:59.040
<v Speaker 4>every time you increase that dose, you've got to go

1:19:59.120 --> 1:20:01.960
<v Speaker 4>back to your allergis off to do that safely under

1:20:02.000 --> 1:20:04.599
<v Speaker 4>guidance to make sure that you don't have an anaphylactic reaction.

1:20:05.720 --> 1:20:07.160
<v Speaker 4>But it exists, Aaron.

1:20:07.400 --> 1:20:10.479
<v Speaker 1>And Okay, So what is the success rate for this

1:20:11.240 --> 1:20:12.000
<v Speaker 1>great question?

1:20:12.520 --> 1:20:16.880
<v Speaker 4>Not perfect? I don't have an exact number. The biggest

1:20:17.040 --> 1:20:20.880
<v Speaker 4>downside with this and another medicine that we'll talk about

1:20:20.920 --> 1:20:24.120
<v Speaker 4>in a minute, is that it doesn't seem to produce

1:20:24.240 --> 1:20:30.439
<v Speaker 4>as long lasting effects as allergy shots do. Okay, but

1:20:30.600 --> 1:20:36.120
<v Speaker 4>it does have significantly increased tolerance for peanuts. Does it

1:20:36.200 --> 1:20:38.240
<v Speaker 4>mean that somebody is going to no longer have a

1:20:38.280 --> 1:20:41.040
<v Speaker 4>peanut allergy? No? Does it mean that they're going to

1:20:41.040 --> 1:20:43.479
<v Speaker 4>be able to accidentally have peanuts or to have a

1:20:43.520 --> 1:20:45.479
<v Speaker 4>little bit of peanuts in something they didn't know had

1:20:45.479 --> 1:20:49.720
<v Speaker 4>peanuts without having a severe reaction or dying. Yes, And

1:20:49.760 --> 1:20:50.240
<v Speaker 4>that is.

1:20:50.479 --> 1:20:53.479
<v Speaker 1>Huge, right, And I imagine that it probably helps to

1:20:53.560 --> 1:20:58.599
<v Speaker 1>then reduce a little bit of the anxiety and fear

1:20:58.800 --> 1:21:00.680
<v Speaker 1>of a peanuts exposure.

1:21:01.080 --> 1:21:05.200
<v Speaker 4>Exactly, aerin exactly, And along those same lines, there's another

1:21:05.320 --> 1:21:09.439
<v Speaker 4>new medication that is really exciting and mere months ago

1:21:09.720 --> 1:21:13.479
<v Speaker 4>February twenty twenty four was approved in the US for

1:21:13.560 --> 1:21:18.880
<v Speaker 4>treatment of food allergy more broadly not es peanuts. And

1:21:18.920 --> 1:21:23.599
<v Speaker 4>this is called oma lizumab. This is a monoclonal antibody.

1:21:23.600 --> 1:21:26.000
<v Speaker 4>Anytime you see a medication like on TV that ends

1:21:26.000 --> 1:21:29.200
<v Speaker 4>in mab, mab is monoclonal animal antibody.

1:21:29.479 --> 1:21:30.960
<v Speaker 1>Wow, I just made that connection.

1:21:33.240 --> 1:21:37.280
<v Speaker 4>So this is a medication that targets, wait for it,

1:21:38.160 --> 1:21:46.040
<v Speaker 4>IgE antibodies. So we are using an antibody, an IgG

1:21:46.479 --> 1:21:53.919
<v Speaker 4>antibody to find and target IgE annabodies in our body.

1:21:54.800 --> 1:21:56.040
<v Speaker 4>What I know.

1:21:57.120 --> 1:21:57.799
<v Speaker 1>That's wild.

1:21:58.280 --> 1:22:01.200
<v Speaker 4>It's it's incredible, Aaron, It's so interesting.

1:22:01.840 --> 1:22:02.400
<v Speaker 1>I love it.

1:22:02.680 --> 1:22:06.720
<v Speaker 4>And it's so like the way that you do this

1:22:06.800 --> 1:22:09.880
<v Speaker 4>is very similar to allergy shots in that people had

1:22:09.920 --> 1:22:12.519
<v Speaker 4>to be getting shots multiple times. You don't do like

1:22:12.600 --> 1:22:14.479
<v Speaker 4>a small dose and build up kind of a thing,

1:22:14.800 --> 1:22:18.240
<v Speaker 4>but you have to have multiple doses over a pretty

1:22:18.280 --> 1:22:20.360
<v Speaker 4>long time period. Most the study that I read that

1:22:20.400 --> 1:22:22.400
<v Speaker 4>was the phase three trial of this drug before it

1:22:22.400 --> 1:22:26.200
<v Speaker 4>got approved was like sixteen to twenty weeks, and then

1:22:26.240 --> 1:22:28.479
<v Speaker 4>they were even checking like if we went for longer,

1:22:28.479 --> 1:22:32.120
<v Speaker 4>would it have a better effect, et cetera. And what's

1:22:32.160 --> 1:22:36.559
<v Speaker 4>incredible is that this showed in this trial where they

1:22:36.640 --> 1:22:39.479
<v Speaker 4>took people who had at least two food allergies, so

1:22:39.720 --> 1:22:42.960
<v Speaker 4>peanut allergy plus at least one other, and the ones

1:22:43.000 --> 1:22:48.160
<v Speaker 4>that they ended up studying were egg, milk, cashew, wheat, hazelnut, walnut.

1:22:48.360 --> 1:22:50.600
<v Speaker 4>That's just what happened people who happened to be in

1:22:50.640 --> 1:22:55.879
<v Speaker 4>the trial. Sixty seven percent of people with multiple food allergies,

1:22:55.880 --> 1:22:58.680
<v Speaker 4>including peanut, were able to tolerate by the end of

1:22:58.720 --> 1:23:02.839
<v Speaker 4>the study at least one thousand milligrams of peanut protein,

1:23:03.240 --> 1:23:09.439
<v Speaker 4>which is equivalent to four peanuts four peanuts. So that also,

1:23:09.479 --> 1:23:12.200
<v Speaker 4>I think gives you a sense of just how little

1:23:12.280 --> 1:23:15.680
<v Speaker 4>peanut it takes for many people with peanut allergy to

1:23:15.760 --> 1:23:18.439
<v Speaker 4>have severe reaction, because in order to be included in

1:23:18.479 --> 1:23:22.520
<v Speaker 4>the trial, they would have reacted to less than one

1:23:22.600 --> 1:23:24.799
<v Speaker 4>hundred milligrams of peanut protein.

1:23:25.000 --> 1:23:27.599
<v Speaker 1>That's wow, right, Yeah, So.

1:23:27.600 --> 1:23:30.160
<v Speaker 4>By the end of the study, sixty seven percent of

1:23:30.200 --> 1:23:34.880
<v Speaker 4>people were able to tolerate at least four peanuts worth

1:23:35.080 --> 1:23:39.479
<v Speaker 4>of peanut protein. Forty four percent of participants tolerated up

1:23:39.520 --> 1:23:41.960
<v Speaker 4>to twenty five peanuts by the end of this trial.

1:23:42.360 --> 1:23:44.520
<v Speaker 1>That's awesome, it's incredible.

1:23:44.760 --> 1:23:48.080
<v Speaker 4>And they saw similar results for cashew, egg milk, wheat,

1:23:48.120 --> 1:23:52.360
<v Speaker 4>hazel nut. Some of these were statistically significant, some of

1:23:52.400 --> 1:23:54.400
<v Speaker 4>them weren't. But here's the other thing I want to say.

1:23:54.439 --> 1:23:56.240
<v Speaker 4>I feel like in a recent episode, we talked about

1:23:56.280 --> 1:23:59.920
<v Speaker 4>the difference between like, is it significant clinically, is it

1:24:00.040 --> 1:24:04.880
<v Speaker 4>significant statistically? Yeah, so sixty seven percent. Depending on who

1:24:04.880 --> 1:24:06.679
<v Speaker 4>you are, that might sound like a lot like Okay,

1:24:06.720 --> 1:24:09.360
<v Speaker 4>there's like a almost seventy percent chance that if I

1:24:09.400 --> 1:24:12.160
<v Speaker 4>have food allergies, if I can get access to this medication,

1:24:12.560 --> 1:24:15.720
<v Speaker 4>I might not be as allergic as I am now.

1:24:16.680 --> 1:24:18.599
<v Speaker 4>But that means there's also like a thirty three percent

1:24:18.680 --> 1:24:22.519
<v Speaker 4>chance that I wouldn't write. But if you break down

1:24:22.520 --> 1:24:25.400
<v Speaker 4>that thirty three percent, there was like a portion of

1:24:25.439 --> 1:24:29.479
<v Speaker 4>those people who did respond to the medication, as in

1:24:29.880 --> 1:24:33.519
<v Speaker 4>before they maybe would respond to like one milligram or

1:24:33.560 --> 1:24:36.240
<v Speaker 4>like a couple of milligrams of peanut protein, and by

1:24:36.280 --> 1:24:39.439
<v Speaker 4>the end they didn't react until they hit maybe three

1:24:39.560 --> 1:24:45.040
<v Speaker 4>hundred milligrams of peanut protein. So it wasn't statistically significant

1:24:45.240 --> 1:24:48.080
<v Speaker 4>for the purposes of the study. But that might be

1:24:48.160 --> 1:24:51.160
<v Speaker 4>the difference between I take one bite of a cookie

1:24:51.280 --> 1:24:53.719
<v Speaker 4>and I realize I'm starting to have a mild reaction

1:24:54.439 --> 1:24:57.120
<v Speaker 4>and I can stop, versus I take one bite of

1:24:57.160 --> 1:24:59.920
<v Speaker 4>a cookie and all of a sudden I'm going into anaphylaxis,

1:25:00.400 --> 1:25:04.519
<v Speaker 4>so clinically that is still significant. There was about fourteen

1:25:04.560 --> 1:25:07.480
<v Speaker 4>percent of people in the study who were true failures,

1:25:07.560 --> 1:25:10.680
<v Speaker 4>as in they did not sorry, they weren't failures, but

1:25:11.200 --> 1:25:16.000
<v Speaker 4>they did not have any improvement in their response to this.

1:25:15.920 --> 1:25:19.680
<v Speaker 1>Medication, which is interesting in and of itself, like why, yes,

1:25:19.880 --> 1:25:22.800
<v Speaker 1>why are some people Why does the treatment work for

1:25:22.800 --> 1:25:24.680
<v Speaker 1>some people but not others exactly?

1:25:24.720 --> 1:25:26.280
<v Speaker 4>And so we don't know the answer to that because

1:25:26.320 --> 1:25:28.160
<v Speaker 4>it does not work for everyone, but it works for

1:25:28.240 --> 1:25:31.040
<v Speaker 4>a pretty good proportion of people. So this was just

1:25:31.080 --> 1:25:36.240
<v Speaker 4>approved and again, like you mentioned Aarin, the potential that

1:25:36.320 --> 1:25:40.519
<v Speaker 4>this has to improve the lives of people even though

1:25:40.520 --> 1:25:43.160
<v Speaker 4>it does not mean that they're not having an allergy

1:25:43.240 --> 1:25:45.240
<v Speaker 4>at all. And we still don't know because this is

1:25:45.280 --> 1:25:48.400
<v Speaker 4>so new and these trials weren't that long. How long

1:25:48.560 --> 1:25:51.960
<v Speaker 4>is this tolerance going to last? We don't know. Are

1:25:52.000 --> 1:25:54.160
<v Speaker 4>you going to have to get this medication again? If so,

1:25:54.360 --> 1:25:56.160
<v Speaker 4>is it going to work as well? There's still a

1:25:56.160 --> 1:25:59.439
<v Speaker 4>lot of unanswered questions, but this medication has been shown

1:25:59.479 --> 1:26:04.000
<v Speaker 4>to be safe and to be effective in increasing tolerance

1:26:04.640 --> 1:26:07.919
<v Speaker 4>to so many of these food allergens, including these multiple

1:26:07.920 --> 1:26:12.320
<v Speaker 4>food allergens, and that has just such a huge potential

1:26:12.360 --> 1:26:17.000
<v Speaker 4>for impact on not only alleviating anaphal access saving lives,

1:26:17.520 --> 1:26:20.479
<v Speaker 4>but also on reducing that anxiety. And that's something that's

1:26:20.640 --> 1:26:24.240
<v Speaker 4>not like, maybe we didn't even emphasize it quite enough

1:26:24.360 --> 1:26:28.920
<v Speaker 4>in last week's episode, just how severe that amount of

1:26:29.000 --> 1:26:32.960
<v Speaker 4>stress can be to never know when you are going

1:26:33.000 --> 1:26:35.719
<v Speaker 4>to be exposed and how severe your reaction might be.

1:26:36.479 --> 1:26:38.719
<v Speaker 4>Who's going to believe you at a restaurant and who's

1:26:38.800 --> 1:26:39.920
<v Speaker 4>not right?

1:26:40.760 --> 1:26:42.519
<v Speaker 1>The fact that there are people who are like I

1:26:42.560 --> 1:26:45.240
<v Speaker 1>don't believe in allergies. I mean, it's like not surprising

1:26:45.320 --> 1:26:47.960
<v Speaker 1>given just the current state of everything in the world.

1:26:48.040 --> 1:26:52.200
<v Speaker 4>But what I know, I know it's not just food

1:26:52.240 --> 1:26:54.839
<v Speaker 4>allergies too. Like we talked a little bit last episode

1:26:54.840 --> 1:26:57.360
<v Speaker 4>about allergic rhinitis, how it can contribute to things like

1:26:57.400 --> 1:27:01.719
<v Speaker 4>difficulties in schools, anxieties. All these allergies have been shown

1:27:01.760 --> 1:27:06.600
<v Speaker 4>to have significant effects on people and their families, especially

1:27:06.600 --> 1:27:09.519
<v Speaker 4>for families with kids with food and other allergies. It

1:27:09.520 --> 1:27:12.760
<v Speaker 4>can lead to social isolation. Like it's a These are

1:27:12.840 --> 1:27:14.960
<v Speaker 4>big deals, and so the fact that we have treatments

1:27:15.000 --> 1:27:19.320
<v Speaker 4>that can help to alleviate that is major and There's

1:27:19.360 --> 1:27:21.720
<v Speaker 4>one more that I want to throw out there, and

1:27:21.760 --> 1:27:27.840
<v Speaker 4>that is nasal epinephrine. Ah nice, even newer erin This

1:27:27.920 --> 1:27:31.559
<v Speaker 4>medication was just approved in August of twenty twenty four

1:27:31.600 --> 1:27:32.720
<v Speaker 4>by the FDA.

1:27:32.760 --> 1:27:33.240
<v Speaker 1>Awesome.

1:27:34.000 --> 1:27:38.280
<v Speaker 4>This is a no needle way to get epinephrine straight

1:27:38.320 --> 1:27:40.960
<v Speaker 4>into your bloodstream in the case of an anaphylactic reaction.

1:27:41.080 --> 1:27:42.680
<v Speaker 4>And I found it I'm good RX for only one

1:27:42.760 --> 1:27:45.519
<v Speaker 4>hundred ninety nine dollars, which is pretty surprising considering it's

1:27:45.560 --> 1:27:47.960
<v Speaker 4>not generic. Because it was just approved. This is a

1:27:48.000 --> 1:27:51.400
<v Speaker 4>really exciting, like really really exciting medication. And I'm sure

1:27:51.400 --> 1:27:54.639
<v Speaker 4>there's a really interesting history of this because I will

1:27:54.640 --> 1:27:56.559
<v Speaker 4>link to a really cool paper that went into like

1:27:56.640 --> 1:27:58.759
<v Speaker 4>what it took to be able to develop this because

1:27:58.760 --> 1:28:01.479
<v Speaker 4>we needed not only the type of nasal sprayer that

1:28:01.560 --> 1:28:04.960
<v Speaker 4>could spray out a fixed dose of a medication, so

1:28:05.040 --> 1:28:07.720
<v Speaker 4>that technology had to develop. We also then had to

1:28:07.760 --> 1:28:13.639
<v Speaker 4>develop a medication that could help other medicines be more

1:28:13.680 --> 1:28:16.840
<v Speaker 4>well absorbed by your nasal mucosa so that we could

1:28:16.840 --> 1:28:20.320
<v Speaker 4>more reliably get Remember I said, how like if it's

1:28:20.400 --> 1:28:22.920
<v Speaker 4>absorbed into your skin, it's not gonna work as well

1:28:22.960 --> 1:28:25.479
<v Speaker 4>as in your muscle. So we had to have another

1:28:25.560 --> 1:28:28.160
<v Speaker 4>medicine to help it get into your bloodstream, and so

1:28:28.240 --> 1:28:31.640
<v Speaker 4>we have that now, and so nasal sprays for so

1:28:31.720 --> 1:28:34.280
<v Speaker 4>many medications, I think they're gonna just take off. And

1:28:34.320 --> 1:28:37.679
<v Speaker 4>so this is one where now there is a nasal version,

1:28:38.040 --> 1:28:39.800
<v Speaker 4>which means that it's going to be easier for people

1:28:39.800 --> 1:28:43.240
<v Speaker 4>to use no needles, easier to give your kid because

1:28:43.240 --> 1:28:45.040
<v Speaker 4>you don't have to poke them, which means kid might

1:28:45.080 --> 1:28:47.000
<v Speaker 4>be less afraid of it. Like, there's just so many

1:28:47.320 --> 1:28:50.879
<v Speaker 4>incredible things that are now possible because there's a nasal

1:28:50.920 --> 1:28:55.120
<v Speaker 4>spray version of an EpiPen. It's called nefi. But all

1:28:55.160 --> 1:28:58.000
<v Speaker 4>of these are new treatment options. What we still don't

1:28:58.040 --> 1:29:01.800
<v Speaker 4>have is prevention aside from what we talked about in

1:29:01.880 --> 1:29:04.800
<v Speaker 4>last week's episode, the leap trial and the eat trial,

1:29:04.840 --> 1:29:08.000
<v Speaker 4>which I looked at back upstands for inquiring about tolerance.

1:29:09.400 --> 1:29:14.240
<v Speaker 4>And these are big deals because we know that early

1:29:14.320 --> 1:29:18.639
<v Speaker 4>exposure repeated exposure can reduce the risk of food allergies,

1:29:18.760 --> 1:29:22.479
<v Speaker 4>especially peanuts, but for other types of allergies, we still

1:29:22.560 --> 1:29:24.639
<v Speaker 4>just don't know. There's a lot of work being done.

1:29:24.720 --> 1:29:27.920
<v Speaker 4>Does treating ezema early in life help to prevent allergies?

1:29:28.040 --> 1:29:31.280
<v Speaker 4>Studies are so far pretty inconclusive, but there's a lot

1:29:31.320 --> 1:29:35.200
<v Speaker 4>of people doing so much incredible research trying to understand

1:29:36.240 --> 1:29:40.280
<v Speaker 4>what are those immunologic triggers and what can we do

1:29:40.400 --> 1:29:43.680
<v Speaker 4>to try and prevent these allergies from starting in the

1:29:43.720 --> 1:29:46.559
<v Speaker 4>first place, at the same time that we're trying to

1:29:46.560 --> 1:29:49.520
<v Speaker 4>develop better treatments for people who already are living with allergies.

1:29:49.760 --> 1:29:52.879
<v Speaker 4>It's an exciting time in the world of allergy research.

1:29:53.280 --> 1:29:56.120
<v Speaker 1>It really is. It seems like there is going to

1:29:56.280 --> 1:30:00.320
<v Speaker 1>just be more and more incredible developments and we're going

1:30:00.360 --> 1:30:02.080
<v Speaker 1>to look back at this time and go, oh, wow,

1:30:02.520 --> 1:30:05.240
<v Speaker 1>we didn't have like we have so much right now. Yeah,

1:30:05.280 --> 1:30:07.200
<v Speaker 1>but we're going to have so much more in the future,

1:30:07.439 --> 1:30:10.639
<v Speaker 1>I know, to bring people home. It's very exciting relief.

1:30:10.760 --> 1:30:13.400
<v Speaker 4>If you want to know more, to learn so that

1:30:13.439 --> 1:30:16.200
<v Speaker 4>you can be one of those future researchers. Oh my gosh,

1:30:16.240 --> 1:30:18.879
<v Speaker 4>thank you. Well directly to some sources.

1:30:20.680 --> 1:30:23.960
<v Speaker 1>Oh wow, I have so many for this, I don't

1:30:23.960 --> 1:30:26.920
<v Speaker 1>even know where to begin, So I'll just shout out

1:30:26.920 --> 1:30:29.640
<v Speaker 1>a few in particular and list the rest on the website.

1:30:29.840 --> 1:30:31.880
<v Speaker 1>I'm going to shout out that one by Noon and

1:30:31.960 --> 1:30:36.599
<v Speaker 1>Cantab from nineteen eleven called prophylactic inoculation against hay fever.

1:30:37.080 --> 1:30:40.080
<v Speaker 1>For the antihistamine and histamine section, I'll shout out of

1:30:40.080 --> 1:30:43.160
<v Speaker 1>paper by Ostrom from twenty fourteen called the History and

1:30:43.200 --> 1:30:47.280
<v Speaker 1>Progression of Treatments for Allergic Rhinitis, and then for the

1:30:47.880 --> 1:30:51.040
<v Speaker 1>epinephrine autoinjector. How about a paper by Arthur from twenty

1:30:51.120 --> 1:30:53.439
<v Speaker 1>fifteen titled epinephrin A Short History.

1:30:53.880 --> 1:30:56.600
<v Speaker 4>I have also a number of papers. A couple that

1:30:56.640 --> 1:31:00.120
<v Speaker 4>I really liked that were more broad overviews was a

1:31:00.120 --> 1:31:02.880
<v Speaker 4>paper from two thousand and eight from Nature Reviews Immunology

1:31:03.160 --> 1:31:06.120
<v Speaker 4>called Treatment Strategies for Allergy and Asthma, and then an

1:31:06.160 --> 1:31:09.080
<v Speaker 4>update from twenty twenty three, also from Nature Reviews Immunology

1:31:09.160 --> 1:31:12.439
<v Speaker 4>called Allergy and Immunotherapy Past, Present, in Future. But I

1:31:12.479 --> 1:31:16.320
<v Speaker 4>have a whole bunch more specifics on anahistamines, more specifics

1:31:16.360 --> 1:31:20.519
<v Speaker 4>on food, allergy treatment, and epinephrine. You can find the

1:31:20.560 --> 1:31:22.960
<v Speaker 4>list of the sources from this episode and all of

1:31:23.000 --> 1:31:25.120
<v Speaker 4>our episodes on our website this podcast wikill you dot

1:31:25.160 --> 1:31:26.320
<v Speaker 4>Com under the episodes tab.

1:31:26.920 --> 1:31:29.840
<v Speaker 1>Thank you again so much to the providers of our

1:31:29.840 --> 1:31:33.519
<v Speaker 1>first hand accounts and for being willing to relive those

1:31:33.600 --> 1:31:35.960
<v Speaker 1>experiences through sharing your story.

1:31:36.400 --> 1:31:38.800
<v Speaker 4>Yeah, thank you so much, we really appreciate it.

1:31:39.479 --> 1:31:41.960
<v Speaker 1>Thank you to Bloodmobile for providing the music for this

1:31:42.040 --> 1:31:43.840
<v Speaker 1>episode and all of our episodes.

1:31:44.200 --> 1:31:46.760
<v Speaker 4>Thank you to Tom Briifogel and Leona Scolacchi for the

1:31:46.800 --> 1:31:47.519
<v Speaker 4>audio mixing.

1:31:47.720 --> 1:31:50.160
<v Speaker 1>Thank you to everyone exactly right, and.

1:31:50.080 --> 1:31:52.519
<v Speaker 4>Thank you to you listeners. We hope that you enjoyed

1:31:52.520 --> 1:31:54.960
<v Speaker 4>this two parter and that you learned a little bit

1:31:55.040 --> 1:31:57.320
<v Speaker 4>or a lot of bit about allergies and how they

1:31:57.320 --> 1:31:58.519
<v Speaker 4>work and why we treat them.

1:31:58.880 --> 1:32:01.400
<v Speaker 1>I've certainly learned all the lot of it me too.

1:32:02.920 --> 1:32:05.519
<v Speaker 1>And a special thank you, of course, to our lovely

1:32:05.800 --> 1:32:09.599
<v Speaker 1>generous patrons. We appreciate the support that you give us

1:32:09.640 --> 1:32:10.880
<v Speaker 1>so so very much.

1:32:11.000 --> 1:32:12.559
<v Speaker 4>We do, we do well.

1:32:12.760 --> 1:32:14.719
<v Speaker 1>Until next time, wash your hands

1:32:14.920 --> 1:32:15.879
<v Speaker 4>You feel the animals