Salbutamol | β₂ adrenergic receptor agonist
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Regular talk therapy doesn't cut it. OCD needs specialized therapy. That's why I want to tell you about NoCD. NoCD is the world's largest virtual therapy provider for OCD. Their licensed therapists provide specialized therapy virtually, and it's covered by insurance for over 155 million Americans.

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Seriously, once we both found our ideal sleep number setting, we just dial it in and let the bed adjust to our bodies throughout the night. Plus, our Climate Series bed keeps us nice and cool through those warm summer months. Why choose a Sleep Number smart bed? So you can choose your ideal comfort on either side. And now, get early access to Memorial Day deals. Save 30% on our most popular smart bed. Exclusively at a Sleep Number store near you. See store or sleepnumber.com for details.

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Welcome, friends, family, and foe, to another episode of Dr. Matt and Dr. Mike's Medical Podcast. I'm your host, Dr. Mike Tenorovitch, and I'm joined by my co-host, the owner of Bunnings Warehouse, Dr. Matthew Barton. How are you, Matty? Basically, I am. Yeah, you're there every week.

Anyway, you'll be proud of this. I bought a treadmill. Oh, good job. Are you using it? I am, but only in 10 second bursts. Oh, why is that? Well, there's a label on it that says stop using it when you're in shortness of breath. Good job. Good job. Today, we're talking about a drug that can be taken when somebody experiences shortness of breath, specifically asthma.

Generally, COPD, chronic obstructive pulmonary disease. This is a drug called salbutamol, probably in the US known as albuterol. And just normally, probably brand name wise, people call it Ventolin.

And this is a little reliever drug that's used to help relieve the symptoms of things like asthma and obstructive airway disease. What are those symptoms? Well, shortness of breath.

Like when you run on the treadmill. That's pretty much the main one. Wheezing? Wheezing. Chest tightness? Yes, a little whine. I say a little whine because his nickname is Wheezy. Is it? Yeah. I knew I had to explain it because you wouldn't have got it. Every listener would have got it. But Matt doesn't listen to music post 1993. I was thinking it said 1960s. The last band you listened to was Jebediah. Yeah.

I think so. I think it was Triple J's Hottest 100 1994 was the last album you purchased. And I think Jebediah's Leaving Home was probably the last song you listened to. Apart from that, it's... I played that to my parents as I left home. I think... Gosh. You...

This morning, though, Matt and I took his daughter to kindy before we recorded this episode. And in the car, Matt made, because I drove, Matt made me put on this. Wait, preface that. No. You asked her what her favorite song was. That's true. And she said, what, the hills are alive or something. She's three, by the way. Doe a deer. She said doe a deer. And I thought she was just being rude to me. I thought she was insulting me.

And so after I said a few profanities back, Matt said, no, she's just saying her favorite song. And so I put on the Sound of Music. So that's probably the last album you ever listened to. True. Sound of Music. All right.

So symptoms of asthma. Okay. Firstly, why would somebody take salbutamol? They take it for what conditions? Is it asthma and some of the symptoms of COPD? Is that basically it? Because then we can talk about what it's used for broadly and then some of the symptoms of those, and then we can go into the history and how it works. Okay.

All right. So here are the technical therapeutic indications for salbutamol. Okay. Slash. Ventolin. Or albuterol. Albuterol. Slash. Ventolin. Slash. Short-acting beta-2 agonist. But we'll get there. Guns N' Roses. Guitarist. Nice. Okay. So why a person would take it is the relief of a bronchospasm. Yeah. Generally...

That will be related to asthma because asthma opposed to chronic obstructive pulmonary disease or CRPD is that it's reversible. That's right. CRPD is not. It's more associated. Both are obstructive, means the airways are being narrowed. Occluded.

But COPD is more associated with the chronic inflammatory mechanisms, whereas asthma is more short-term exacerbations. It could be a chronic condition that you've had it for your life or long periods of life, but the bouts are reversible. So, yes. So emphysema, chronic bronchitis, those airways remain narrowed. Yeah. It's because they're chronically inflamed or they've got chronic...

that are occurring in the airway, which is leading to their obstruction. Whereas asthma... You can have a normal airway. And then you have kind of a reaction to something like an irritation or an allergen or even to exercise. Yep. And then you get a bronchospasm, so a narrowing more to do with the muscle itself opposed to other processes. Yep. And the salbutamol or American one? Albuterol. Albuterol. That...

reverses that spasm and opens it back up. So the spasming airways, we know from anatomy and physiology that when you look at the airways, you start with the oral cavity, then you go to the

the pharynx and the larynx. So the pharynx is the throat. The larynx is the beginning of the airway. So like the vocal cords. Yep. And then from there it goes down to the trachea and then splits into two for the bronchi, left and right main stem bronchi. And it continued to split until it creates smaller bronchioles, which are what, one millimeter diameter-ish? I remember. And then they split maybe 23 times. So from the bronchi, it splits 23 times until you're at what we call the terminal bronchioles, right at the very end of the bronchi.

where they turn into respiratory bronchioles, which are basically alveoli. Now it's the bronchioles that have the muscle and the bronchi and trachea don't really have much muscle tissue, which means that when you get this bronchoconstriction, a lot of people think it's like the throat that's closing up. Like I, I,

i.e. the trachea and the bronchi, but it's not. They're not really narrowing. It's the smaller airways that are narrowing. So the bronchioles, so deeper, deeper, deeper into the lungs. And so this is where the effects of asthma occur, the bronchoconstriction, but also this is where we need this particular drug to have its effect deep into the lung tissue, which will make sense when we start talking about how this drug is administered. Yeah.

and what people need to do to bring it into that airway. Right. Should we talk about the history? Do you have anything about the history of salbutamol? A little bit. Well, it goes back to probably the precursor for salbutamol being adrenaline. Oh, right. So we did know for some time, it was probably 1800s, that...

Something came out of the adrenal gland of importance because if the adrenal gland was damaged, you could develop certain diseases. One being Addison's disease, which was named after Thomas Anderson, who realised if the adrenal glands were damaged, some chemical inside it would then cause whole body effects. You know, if I was to discover that chemical, I'd call it adrenaline because it's the adrenal glands. But anyway...

Well, from then they started to, no surprise, experiment again on animals. But in this case, you'll be glad to hear it was cows, not dogs. Don't know why I'd be glad to hear that. So it was the removal of adrenal glands from bovine organs.

And they found that the, again, it would result in death. Right. But then they started. So they understood that it was important for life. Then they started to, a bit like what you spoke about when we did renin. Okay. Basically, they just mushed up the kidney, right? And then they developed or discovered a chemical in it being renin. Yeah. Because that was where its name came from, correct? Yeah.

In terms of the adrenal gland, they found the same thing. If you mushed up the adrenal gland and kind of like you squeeze it like a sponge. Yeah, I'm sure that's what they did. The chemical that came out of it, if you threw it onto blood vessels, it would cause blood vessels to constrict. Yeah. But if you threw it in the blood, it would cause the blood pressure to go way high. Yeah. Heart rate would go up really quickly. I think that's what they wrote in the article. Oh, blood pressure went way high. Yeah.

And, but- Matt's a scientist. The airways would open up. Right. So you're saying that you throw adrenaline at somebody into their body specifically, blood vessels, broadly blood vessels constrict.

The constriction of the blood vessels, the way I explain it with my students is like if you've got a hose and you put your thumb over the end of the hose, you narrow it, the blood's going to back up, it increases blood pressure. So that's increasing blood pressure. But in the airways, they dilate and open up so you can get more air in. And this makes total sense when you think about why the body in normal, quote unquote, natural situations...

When the body floods itself with adrenaline, it does it when it's scared, right? So when you're scared, you need to mobilize the important functions and leverage the important functions of the body to keep you safe in that moment. And the things you need to do is you need your heart rate to go up so that you can pump more blood to the muscles of your body.

To do that, it triggers heart rate going up and forceful contractions of the heart, but also squeezes the blood vessels so the blood pressure also goes up so you can deliver more blood more forcefully to the tissues. The blood vessels of your muscles actually dilate so the muscles get more blood and oxygen.

But you also need more air getting into your lungs so you can deliver the oxygen to the muscles so you can fight or run away. And so that's why your airways open up. Yep. So you're saying that they found out by springing the bovine adrenal glands like a sponge and dripping... More or less, more or less. Dripping the output into somebody's... I'm sure it was a little bit more refined than that. I'm sure. But it was a corrupted chemical... Did you win? Yep. It wasn't until...

I could probably find. I'm sure you could. The start of the 20th century, so early 1900s, a Japanese scientist isolated it and purified it. Right. And then, interestingly, the person before that caught it

epinephrine because of was that Greek? Epinephros. But then the Japanese scientists named it adrenaline because that's a Latin. Yeah. So that was then discovered. Now it was through all the systems that you just mentioned of the sympathetic nervous system. It was used probably with

a degree of success with asthma, but what would the side effects be? Well, if you think about what the normal side effects are when you stimulate the sympathetic nervous system, heart rate going up, pupils dilate,

Airways open up. You probably get a little bit jittery, right? So if you're running away from a dingo... Sorry? If you're running away from a dingo... I've never run away from a dingo, Matthew. No, you haven't been to Fraser Island? I've been many times. The dingo's run away from me, mate. Okay. So a dingo is a... What would you say? It's a wild dog. A wild dog in Australia. Yeah. So if you're getting chased by a dingo... Let's say a bear. No, we don't have them in Australia. Koala bears...

Which we shouldn't call them bears. No, they're not bears. That's vicious. No, they're not vicious. Oh my God. A koala bear. How much can a koala bear? No, it's a quokka. You've got a quokka coming out, and if you don't know what a quokka is, Google it. Q-U-O-K-K-A. Probably the cutest animal you've ever seen. That will kill you. On Rottnest Island.

Which I believe is called that because when they first visited, they thought they were rats. And it's a... Rat nest. Yeah. Rat nest island. I like that. Is that true? I don't know. I could have just made that up right then. So...

What are you trying to say? So if you were, let's say, probably a child in the turn of the 20th century and you were suffering from asthma. All right, let me put myself in this situation. And for those of you listening, if you hear some loud noise in the background, it has started to pour outside. It is raining very heavily where we are. So that's the sound. But you said, so, okay, let me just put myself in the place. I'm a 19th century person.

Yep. 900s, turn of the 20th century. Okay. I'm a chimney sweep. I'm 12 years old. Shine your shoes for a penny, governor. I'm in England, obviously. Yeah. All right. Hello. What we got here then, eh? Okay. What you want me to do? Well, are you here for your shortness of breath, mate? I don't know what that means. I ain't very educated, mate. I went to grade three and that's it. But I can't breathe no good.

Okay, so with that, with your, let's say, assumed asthma. Yeah. We're going to give you a chemical that we've just purified called adrenaline. Don't know what any of that means, mate. But when we give you this systemically into your blood, that should help you breathe in. Oh, right. That sounds good. I need to breathe. These damn chimneys are clogging up me lungs.

I can't tell you how often I hear, oh, I'm a little OCD. I like things neat. That's not OCD. I'm Howie Mandel and I know this because I have OCD. Actual OCD causes relentless unwanted thoughts. What if I did something terrible and forgot? What if I'm a bad person? Why am I thinking this terrible thing? It makes you question absolutely everything and you'll do anything to feel better. OCD is debilitating, but it's also highly treatable with the right kind of therapy.

Regular talk therapy doesn't cut it. OCD needs specialized therapy. That's why I want to tell you about NoCD. NoCD is the world's largest virtual therapy provider for OCD. Their licensed therapists provide specialized therapy virtually, and it's covered by insurance for over 155 million Americans.

If you think you might be struggling with OCD, visit NoCD.com to schedule a free 15-minute call and learn more. That's NoCD.com. So let me just start this by saying, I love my husband. However, when it comes to our sleeping preferences, we couldn't be more different. That's why the Sleep Number Smart Bed has totally changed the game for us. Ever since we got it, we both sleep through the night at our ideal firmness and wake up feeling refreshed and resentment-free.

Seriously, once we both found our ideal sleep number setting, we just dial it in and let the bed adjust to our bodies throughout the night. Plus, our Climate Series bed keeps us nice and cool through those warm summer months. Why choose a Sleep Number smart bed? So you can choose your ideal comfort on either side. And now get early access to Memorial Day deals. Save 30% on our most popular smart bed. Exclusively at a Sleep Number store near you. See store or sleepnumber.com for details.

Okay. Governor. Now. When I'm done, I'll shine your shoes for a penny. Okay. Got it. Got it. You got a penny? Now, what is, what, what's some of the side effects of giving you this Mr. Chimney Street sweep? Street. Sweep of the street. Do you want me to still do it as the kid? No. Um, I would say that my heart rate's gone through the roof. Yes. Right. Um, I've gone pretty pale.

Because the blood has shunted away from my skin and gone to my muscles. Pupils have dilated. Airways have opened up. My breathing rate has probably changed. Your breathing rate's better, but your side effects have been hypertension, heart rate. Your pupils are really big. Probably a bit jittery because of the way it's affecting the mobilization of energy stores and because of the muscles. And it's probably...

around with the potassium within my bloodstream. So it can stimulate sodium potassium pumps and chuck potassium or hide potassium into the cells. So that could probably affect the way my muscles are contracting a little bit. Okay. So with all that said, you have too many side effects that's potentially going to be beneficial. So we need to look for an alternative because with the sympathetic nervous system where this drug is binding to alpha and beta,

Yeah. Right? Yeah. So we really only want it to be selective for one type. So what the scientists then... Wait, can we talk about these alpha-beta receptors for a sec? We haven't spoken about it yet. Yeah, you can do that. Okay, so...

Adrenaline doesn't just bind to beta receptors. And I don't even think we've been too specific here. But we said that when you throw adrenaline in somebody's body, you get all these effects that we just spoke about. But adrenaline needs to bind to specific adrenaline receptors, which we call adrenergic receptors. And there's different types. There's alpha and there's beta.

and you've got alpha-1 and alpha-2, and you've got beta-1 and beta-2. There is a beta-3, but it's found on fat tissue, and it promotes lipolysis, which isn't necessarily relevant here. So you can talk about functionally alpha-1, alpha-2, beta-1, beta-2. Now, they're all located on different tissues, and there's a lot of overlap in which you're going to get different receptors located on the same tissue, which might be relevant in a sec. But broadly speaking, you've got the beta receptors, so beta-1...

is located on the heart and it stimulates that organ to do its job. So when you throw adrenaline at beta one, stimulates the heart to contract. There's one heart to think of beta one. I think it's also on the juxtaglomerular complex. So it stimulates, um, the, um,

I think renin, this is where it stimulates renin to be released to increase blood pressure. When you think of beta-2, we've got two lungs. So when you throw it at beta-2, it will tell the tissue to inhibit beta.

Meaning, if you throw it at the lung tissue, it tells the muscle in the lung to relax. So the muscle relaxes and opens up, and so you get more air in and out. Beta-2 is also on some blood vessels. Blood vessels, which you want to relax them. To dilate. So they're going to be on the muscles, right? Because we said you want to increase blood flow to the muscles when you throw adrenaline at them. And then you've got the alpha. The alpha are found at presynaptic terminals to self-regulate, so they inhibit blood flow.

So it's like the beta ones, it results in an inhibition, inhibit more adrenaline to be released. And then you've got, I think it's the alpha two are located on blood vessels as well. No, other way. Alpha one. Oh, the alpha one are on the... Eye, so it's going to dilate your eye, but also blood vessels, which are going to constrict. And the two feeds back on itself.

Yes. Two is the self-regulation. It inhibits more adrenaline. And then the one is tells the muscles of the pupil to constrict, which actually dilates the pupils. So it's not resulting in any relaxation and tells the blood vessels to constrict to increase the blood pressure. We settled that because that means if you throw adrenaline at somebody, you're going to have a whole range of effects depending on which receptors it binds to. And if you're flooding the body, you get all of the effects.

But Matt just said we don't want all of the effects. We only want the specific relaxation of the muscle in the lung tissue, the bronchodilation effects. So we need to make beta-2 specific drugs. Yes. So please continue. So the next step was to develop a drug called isoprenoline, which basically replaced an amino group on the adrenaline with an iso, what would you have called it?

I don't know. You're reading your notes. I don't know. It's not in my notes. Matt and I don't write the same notes. We prepare separately so that I can correct him when he's wrong. And so that's pretty much the only reason. I had it written down. I just can't find it now. But effectively it just- Isopropyl group. So it slightly changes the drug. Yeah, which makes it- It made this particular medication, isoprenoline, beta-specific.

Right. Okay. So it got rid of all the alphas. Oh, but beta one and beta two. The beta one was still, it was better for the blood pressure, but it also made the person get always. Had its chronotropic effect, increasing heart rate. Heart rate and heart force. Yeah. But it was effective on the lung. So that was better, but not perfect. And then they did further. How are they taking this?

Good question. I'm not sure. I didn't look into that. But then we did a slight modification from that and then we developed salbutamol, which became much more beta-2 selective. Yes. And this is taken as an inhalant, right? Usually inhaled, that's right. So aerosol or nebulized, things of those nature. Which makes sense because one, it's getting to the target tissue. You can just inhale to get to the bronchioles.

Two, it's probably resulting in a reduced crossover effect where it is reduced to inhibit the heart. Obviously, it's going to get absorbed through the lung tissue into the bloodstream and you can still have some degree. Because even with salbutamol, right, you do get some degree of heart stimulation. Yes. It's still not perfect. Yeah. So you do get some degree of sympathetic stimulation. So...

So, it, salbutamol is a very, because you suck it in through the airways, you get the bronchodilation because in a way it's trying to mimic adrenaline, right, in the airways, dilating it. It's pretty short lasting, right? Yeah, like two to four hours.

I can't tell you how often I hear, oh, I'm a little OCD. I like things neat. That's not OCD. I'm Howie Mandel and I know this because I have OCD. Actual OCD causes relentless unwanted thoughts. What if I did something terrible and forgot? What if I'm a bad person? Why am I thinking this terrible thing? It makes you question absolutely everything and you'll do anything to feel better. OCD is debilitating, but it's also highly treatable with the right kind of therapy.

Regular talk therapy doesn't cut it. OCD needs specialized therapy. That's why I want to tell you about NoCD. NoCD is the world's largest virtual therapy provider for OCD. Their licensed therapists provide specialized therapy virtually, and it's covered by insurance for over 155 million Americans.

If you think you might be struggling with OCD, visit NoCD.com to schedule a free 15-minute call and learn more. That's NoCD.com. So let me just start this by saying, I love my husband. However, when it comes to our sleeping preferences, we couldn't be more different. That's why the Sleep Number Smart Bed has totally changed the game for us. Ever since we got it, we both sleep through the night at our ideal firmness and wake up feeling refreshed and resentment-free.

Seriously, once we both found our ideal sleep number setting, we just dial it in and let the bed adjust to our bodies throughout the night. Plus, our Climate Series bed keeps us nice and cool through those warm summer months. Why choose a Sleep Number smart bed? So you can choose your ideal comfort on either side. And now get early access to Memorial Day deals. Save 30% on our most popular smart bed. Exclusively at a Sleep Number store near you. See store or sleepnumber.com for details.

Yeah. But it comes on quickly. But it's not used to prevent one coming on necessarily. It's used to relieve the symptoms of it occurring. Yes. Sometimes it's used prophylactically for exercise-induced bronchospasm. Sure. So if you were to get asthma that's provoked by exercise, you might take it before the exercise, but generally...

If you were to have asthma, you would probably want a medication regime that you would take to regulate or prevent, not so much as a preventer, but just kind of a controller. Yep. Whereas you'd use salbutamol or what was the... Albuterol. Albuterol, yep. As the reliever. Reliever, yeah. If it wasn't really knocked off. And so this sort of, from my perspective, stop me if I'm getting ahead of it, is important to know because...

So salbutamol, you know, it is what we call a short-acting... Saber. Saber, short-acting beta-2 agonist, right? So one short-acting, it's a beta-2 agonist, stimulating the beta-2 receptors. It's a reliever, relieving the symptoms of asthma, resolving the bronchodilation, but shouldn't necessarily be used all the time to prevent symptoms. No, no. And there's reasons for this. So one is...

of the sympathetic activation. So you're increasing the sympathetic nervous system activity, which like we said, can increase heart rate.

And can also increase arterial stiffness and reduce vascular function, at least temporarily can do that, which is pretty harmless short-term. But there's concerns raised in the literature that chronic long-term use of this could have its cardiovascular effects. So what they basically say is that, you know,

Because of its effects, overuse can exacerbate some issues. So it can also promote inflammation through overuse, right? So it can have pro-inflammatory effects. Is that local or is that a whole body? It's in the vasculature and also in the lung tissue itself. Okay. So it can lead to elevated arterial stiffness, impaired endothelial function, etc.

And the thing is the cardiovascular changes, they're not solely due to salbutamol, right? They're also due to asthma, right? Because when your airways close up, it affects the way your heart works. It affects your blood vessels and everything like that. So it's sort of this playing effect as though, well, is it salbutamol? Is it necessarily the asthma? But they also say that salbutamol

should be combined with inhaled corticosteroids, right? Which can counteract those inflammatory effects of the salbutamol. And so that's that pairing that they tend to do. And because- Yeah, my understanding with asthma, there's like a five-tiered system.

which really speaks to how well the asthma is controlled, probably the severity of your asthma and the symptoms that are on a regular basis. And the tier five would be the most severe end, which you're using quite regularly.

Not invasive, but quite... Infrequently. The medications that would be utilized for a person with stage 5 asthma would be quite heavy hitting. Like adrenaline? Maybe not quite that level, but you're using high dose steroids, you're using another host of other medications to try to keep the asthma in check. But when you're trying to control the asthma to prevent the bronchospasm, it would be fairly common to have a steroid that's

That's there all the time. Yeah. And then probably a more of a long acting beta agonist. And then you're only using the salbutamol for the short term relieving kind of. Yeah. Like the rescue inhaler. Yeah. Sort of thing. Yeah. And it's important because again, you can have,

Overuse side effects, right? And I'm sure anyone who's taken too many puffs of their Ventolin has noticed that they've experienced some tremors or shaking, the tachycardia, the increased heart rate, headache maybe. Yeah. The blood vessel dilation changes. You can also have some degree of tolerance.

Develop a tolerance of it over time. But you can also get hypokalemia from this. Hypo. Hypo. That's what we alluded to earlier because sympathetic stimulation can trigger the ATP pumps and that throws sodium out of the cell but throws potassium into the cell. So it sort of hides the potassium from the blood. So it looks like you've got a hypokalemia.

And that changes the way that muscles contract and fire off. Probably one of the reasons why we have the tremors, you can get some weakness. I think the tremors also is to do with the beta-2 receptor. On the muscle? On the muscle. Yeah. And it's just generating. And I think it's more fine tremor, like hands. Yeah. Yeah. Anything else you had about salbutamol or albuterol? Were you happy with the,

the mechanism of action? Yep. Yeah, I think that's fine. We're covered? Yeah. Okay. So really it's a medication, a very successful medication that is used as a reliever within asthma. It's known, as we've said, as a short-term beta agonist, but there are

more developed because it's pretty much out of your system within four hours. It's not overly good for long-term maintenance of asthma. So we have developed, not we as in you and me. No, but me, I have. I've developed this.

Smart people, smart scientists have developed a longer actin beta-2 agonist. Generally, salmeterol is an example. And they're known as labbers, long actin beta agonist. Long actin beta agonist, not short. I'm not using that. I'm not using that suffix, labbers. So that would probably be used more commonly in the maintenance. So these are the moles? These ones? Yeah. No, these are sabbers.

Ah, that's right. Cause yeah, I haven't said that before. Short acting beta to agonist. Oh yeah. And the lab was, we'll be long acting beta to agonist. Sorry. I was thinking about the suffix, not it's mechanism of action. Oh, okay. My bad. So that's, that's really sub-unimal. Look, I think that's pretty good. Again, I'm just going to iterate the fact that please, when it comes to, uh,

What we're trying to deliver here is educational content so people understand what these drugs are and how they work. This is for students who are studying, anyone that's interested to understand what these things are. None of this is to tell you what to take and how to take it or anything like that. We're not prescribing or telling you what to do. Please don't go, Dr. Matt and Dr. Mike said this and therefore I'm going to do it, that we don't offer advice.

in that sense. So, plus we're not qualified to offer you that advice, especially not Matt. So, or me to be honest. So please, hopefully you find this content educational and we will speak to you soon, okay? Music

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