hi students welcome to chapter six your adrenergic sympathomimetic bronchodilators this is your first lecture on an actual category of medications and it just so happens to be a category medications that we use quite frequently um this will probably be a classification of a drug that will be your very first drug that you give as a respiratory therapy student so it's important that we get started with this okay so let's first start with the clinical indications for our adrenergic bronchodilators this is going to when stimulated relax the smooth muscles in the airway when we have the presence of reversible obstruction so sometimes we have changes that might occur in the tracheal bronchial tree that can create the sound of wheezing and it might sound like asthma but those changes if they are not reversible do not respond to these types of medications so what has to be present for this group of medications to work is truly bronchospasm so the muscles around the airways are constricted and and making the internal diameter of the airways a lot smaller and i have a good picture of that but the types of disease that we see are bronchoconstriction and is asthma and asthma can be described as acute chronic or exercise induced bronchitis bronchitis can cause irritation of the airway and then that irritation can lead to some bronchoconstriction so that might help with that emphysema is another one that because those are some chronic changes that occur that are associated with copd we can still see some irritation of the airway associated with copd and emphysema and it might have some reversible airflow obstruction the amount of airflow obstruction that's reversible in diseases such as copd are relatively small but we still can see some changes in some patients might do well with an adrenergic bronchodilator and then bronchiectasis is a chronic disorder that has to do with um an accumulation of a lot of secretions and we're going to get into bronchiectasis later but it is also a disease that turns more chronic than it does acute and some of the changes that happen in the airway um are permanent and they have more of airway remodeling that occurs because of their their disease and how long they've had the disease um but in some there is some reversibility still so again i i have to stress to you that's what's really important about these adrenergic bronchodilators is that there has to be reversibility of the airflow obstruction and it has to be from that bronchoconstriction piece this is just a youtube video for you to watch i'm not going to do it now with this video as far as time is concerned but do take a minute and look at how this bronco constriction does occur so here's just a a picture that i found on the internet to show you what's going on with how this airflow limitation and its reversibility piece is problematic for our patients in particular that have asthma so we have the internal um mucosa and um epithelial cells on the inside of this cross section of a um a piece of bronco bronchus you could just call it that and on the outside we have these muscles you see these darker red areas and if we were to take this cross-sectional view we see that we have a fairly healthy amount of internal diameter it's not compromised whatsoever so we don't have any change in resistance or airflow obstruction but when we have bronchoconstriction and these are the muscles they're constricting and we do have some inflammation in here this is all inflam inflammation going on and then we've got some mucus production which also inhibits normal airflow and so when we take that cross-sectional view our light light light blue area here is all that's participating in airflow movement and our internal diameter is drastically changed what these bronchodilators do is all that they do is relax these muscles all right so they are not responsible for reducing the inflammation here nor is this drug responsible or capable of getting rid of the mucus so that's really what we're targeting is anything that has that that muscle that's going to be constricted and we can get to the receptor sites with this albuterol or our adrenergic bronchodilators that we're talking about here and get those muscles to relax that's our hope all right so in the lungs when it comes to the sympathetic nervous system and that's what we're really talking about and we are working with adrenergic sympathomimetics so the bronchodilating action really does come from one of the three receptor sites that we would see in the sympathetic nervous system at the receptor site and that would be our beta two all three of these the alpha the beta one and the beta two are all potential receptor sites in the lung and in the heart um and in the blood vessels around the lung um and when we're using a bronchodilating agent it does look a lot like norepinephrine or epinephrine because that's our neurotransmitter and so if we want to stimulate the alpha the beta 1 and the beta 2 receptor sites these adrenergic bronchodilators have to look a lot like norepinephrine so that they have that ability to come into the receptor site and elicit a response now when norepinephrine is released and in the area it's going to stimulate all three of these we do have bronchodilators that are a little bit more specific by just changing them just to smidge their chemical composition just a bit they can be a little bit more specific for the beta two to make it more about just relaxing the bronchial smooth muscles but when we do stimulate the alpha receptor sites we have the vessels the blood vessels will constrict and that's called vasoconstriction and that's our effect that we're going to get there the beta 1 sites even in the lungs can increase the heart rate and contractile force of the ventricles of the heart so when we do give sorry went too fast there back up so when we do give um some of these non-specific bronchodilators we're going to hit all of these receptor sites so we are going to have some of those reactions that we don't want but i'm going to talk a little bit more about it being a little bit more specific to the beta2 when we go down into this powerpoint further all right so the beta receptor these bronchodilators will bind to the beta receptor and ultimately causing this chemical reaction to occur and this is why we end up having this bronchodilating effect because there's this chemical that is made intracellularly called c-a-m-p and c-a-m-p is what causes the smooth muscle to relax and so once we um stimulate the beta-2 in particular is where we're going to get camp formation and having it released and and having that bronchodilation occur so that's a good thing we want that to happen but at the same time what we could be doing is stimulating the alpha receptor sites because most of these adrenergic bronchodilators that look a lot like norepinephrine can stimulate the alpha receptor sites and the downside of that though stimulating those alpha receptors may lower the synthesis of that intracellular ca and p so it can be counterproductive so we do want to try to avoid that alpha receptor stimulation if we can when it comes to the types of adrenergic bronchodilators we have two types they're just categorized and either short acting or long acting when it comes to the short acting they have a couple of subs subcategories as well that we're going to talk just a bit about but they both target the beta 2 receptor site and the smooth muscle of the airway and they can be very specific so that's good so our indications for our short acting these are our rescue agents so this is our go-to when we have an acute exacerbation or those signs and symptoms that come up that say that we have this acute reversible air flow obstruction like what we see with asthma an example of that is albuterol level albuterol or zopanx the x is a z sound it's zoponex zopanx is um not really being used that much anymore your book still talks about it um and i'm going to talk a little bit more about lever albuterol or zopanx um in a few slides but we're not seeing it as much because of the cost it's actually quite costly when compared to albuterol and it doesn't have the anticipated better outcomes that they were hoping for with soap and ex um and they're just not materializing so people are saying we're not going to carry it anymore hospitals are not and they're not going to order it as much if there's a patient that comes in that regularly gets open x at home and it controls their asthma relatively well they're still going to use it for them but they're not going to be actively pursuing new orders for zopanex all right and then our long acting these are great are long acting are not rescue but these are more for maintenance or control so this is what we're going to give patients that um have some still some serious issues with bronchoconstriction and it should reduce that nocturnal symptoms because our short actings will only last no more than six hours and for patients that still have um the triggers for their asthma still going on in their body they have breakthrough symptoms in the middle of the night and they're losing sleep and it affects their quality of life and so for patients who can get better control over their asthma they're going to use these long acting adrenergic bronchodilators so salmeterol for motorol and arfamotorole and then your book talks about endactoral and olodacterol as well but mostly in san diego we use one of these three but some of these newer ones are becoming a little bit more popular these are typically convey combined combined with an anti-inflammatory medication because another component of asthma is inflammation as that picture showed you there was that inflammatory piece and so when we're going to use an anti-inflammatory um it's usually a steroid and they're usually combined together because they actually complement each other well so we rarely see just one of these long actings just a standalone whether it's an mdi or a dpi that's typically how they're formulated they're usually combined with a longer acting steroid okay all right and then one other thing that's worth mentioning is that we can call some of our um adrenergic bronchodilators as ultra short acting because their duration is less than three hours um before we had albuterol or level level albuterol we were really using just epinephrine or what we call racemic epinephrine i'm going to talk a little bit more about what that is it's just racemic epinephrine is is really just implies that it's something that's made in the lab and it's not and it's synthetic it's not naturally found but we used to give epinephrine to patients for their asthma and because the duration is less than three hours it's considered ultra short acting but it also has a lot of side effects too because it's not as specific just to the beta two receptor sites it'll hit those alpha and the beta ones and then our albuterol in our level albuterol and what has really fallen by the wayside we're not using metataranal anymore um and so you could just kind of forget about that one just know that their albuterol and our level albuterol which is also known as ours open x is considered a short acting and its duration is four to six hours and then our long acting is a duration of 12 hours um and that's more for maintenance and control and that's our salmeterol for motorola and arfomotorol all right so let's get down to really what these are um the chemical structure and everything like that and what they look like and what we could see with them when we give them to patients so technically um any of our sympathomimetic bronchodilators are catecholamines epinephrine is considered a catecholamine or they're also considered a derivative of catecholamine because it's just a smidge different so that it's not exactly like epinephrine and it actually can be better if it's a derivative because it can be more specific to the beta2 receptor site so basically our catecholamines do mimic epinephrine and so there are some inherent side effects that we can see with giving a catecholamine such as tachycardia an increase in blood pressure we will get that smooth muscle relaxation that's what we're trying to get that's what we're after but we also can see glycogenolysis which is breaking down of glycogen so that can have effect on um like the patient's metabolic given a metabolic issue because it inhibits the proper use of glucose some patients can have skeletal muscle tremor or also have cns stimulation so they're usually like wide awake and have trouble sleeping if we're just giving these catecholamines this is just the basic structure of a catecholamine or not or basically what epinephrine looks like you don't need to memorize this or anything like that but it is broken down as a bin benzene ring with two hydroxyl groups and this amine side chain here it's really the amine side chain when we're going for a derivative of a catecholamine that gets um adjusted a little bit it gets changed just to smidge and that's what actually gives it more specificity to the beta2 receptor site so when it comes to making a synthetic adrenergic bronchodilator or racemic epinephrine this um type of adrenergic bronchodilator can exist in two different arrangements and it actually produces what we call isomers and so isomers are really just mirror images of each other um that are really not superimposable so in other words if you took your hands and you went like this you can't put one hand on top of the other like in this direction and have them really be matching the only way to do it is to flip it around and have it like that but an isomer is a mirror image so they're images like this but you can't put them on top of each other and they're not identical so when we do make a synthetic bronchodilator they're usually made with what's called an r isomer or the right isomer or the s isomer is considered the left isomer and in some cases some say that that s isomer is considered inert so that's not the piece that actually has its effect in that bronchodilation piece but they are definitely similar physical and chemical properties when it comes to these two isomers and albuterol is synthetic with 50 50 mixes of the r and s isomers um and they do have different physiological effects but basically the r isomer is what is responsible for the bronchodilation piece that occurs now natural epinephrine so if we were to get it naturally out of a human person is the um is our isomer only but when we make a synthetic epinephrine and we call it racemic epinephrine it has both the r and the s isomer so this would be our racemic epinephrine and so we have the r and the s isomer and you can see that they are mirror images of each other it's just worth mentioning all right so epinephrine itself if we're going to use synthetic epinephrine or racemic epinephrine it can be given as a bronchodilator and in fact it's considered a potent catecholamine bronchodilator but because it's so similar to norepinephrine it will stimulate both the alpha and the beta receptor sites so we're going to get all those other side effects that we really don't want such as tachycardia increased blood pressure tremor headache and insomnia and so like i said this epinephrine is a synthetic racemic mixture and it can be given both inhalation and in an and subcutaneous injection so that's like your epipen um and so we can give it for for um allergic reaction and we can give it for asthma exacerbation as well so just under the skin that subcutaneous injection all right so the keyhole theory and beta2 specificity is really referring to what we've been able to do with those catecholamines and make them the derivative of a catecholamine and that's really what our albuterol is we've been able to tweak it just a bit um so that it can be more specific just to the beta two and so when we finally came out with albuterol what we were noticing because it had this beta 2 preferential is that patients were experiencing far fewer side effects and so that was a good thing so to break it down a little bit the epinephrine is equal parts of alpha and beta when it comes to stimulation what came before albuterol was the metaproterenol um and it was less alpha but it was definitely a strong beta in both beta 1 and 2 so that still came with side effects and then lastly they started messing with that catecholamine side chain a little bit more and we were able to get to be a little bit more beta-2 specific or preferential so again eliminating not completely but mostly those side effects that we are unwanted all right like any drug there's got to be a way to metabolize it and when we're talking about the metabolism of a catecholamine we have to talk about this cytoplasmic enzyme comt that is found in the cells and it is what really knocks off the albuterol from the receptor site and it is what will be playing a role in the metabolism of the catecholamine and that's what gives us the length of time in that which it will last but epinephrine though if we were to give epinephrine there's no oral administration form of epinephrine because it gets completely inactivated in the gut and the liver so epinephrine again is either inhaled or subcu also our catecholamines become inactivated by heat so we want to keep them at nice room temperature they usually need to be protected from light and from air but not to worry we're able to you know keep them in foil packages or in dark glass bottles and we only pull it out and expose it to air when we're just about ready to throw it into that small volume nebulizer and give it to patients all right so our catecholamines can be broken into two different types and that's what i was talking about earlier a resourceanol and so the siligenin is really what we're working with today we're not using a lot of resource animals anymore all right so the resourcinal agent is better for maintenance therapy it does have a longer duration of of action as four to six hours but it takes longer for a peak effect and the examples are ones that we really don't use that much anymore terbutaline and metaproterenol so terbutaline is still around but it actually causes uterine relaxation and can be given to moms who have pre-term labor so if we've got some contractions going on and they're not too far where the baby or the contractions have led into a progression into labor further than it can be stopped you could give terbutaline um and it causes that smooth muscle of the uterus to relax and then metaproterenol because it has a lot of beta-1 effects too is not being used as much now that beta i'm sorry now that albuterol has come in and we're not um using it as much so the siligenin agent is r albuterol it resists inactivation by enzymes in the gi tract so that's good news because this can be in a pill form now albuterol does come in a syrup or a pill form for patients who cannot take an mdi or a nebulizer but most likely you'll be giving albuterol as an mdi or a nebulizer so our albuterol is one that really gives us that beta two preference um a good thing is that it is affected by mouth it will peak in about an hour and the duration is up to six hours so it's all good all right so this is the one and only slide on level albuterol or zopanx because we're not really using it that much but i just wanted to mention that in case you come across that sometimes children's hospital will continue to use um zopenex again if it's a patient that's receiving it at home they'll continue to use it so um like i was telling you the the formulation of like albuterol are all synthetic racemic mixtures so it has both the r and the s isomer and equal amounts our zopinex or level albuterol is pure r isomer because they believe that s isomer is inert but some were believing that the s isomer was maybe responsible for some other of the um other side effects um and giving us like the increase in heart rate and the tremors and things like that so they thought well if they could make level albuterol and get rid of the s isomer and just use our isomer we shouldn't see as many side effects well it really didn't work out that well and patients were still not getting the amount of relief that they were getting from the albuterol and that's really why they're not using it as much and it's more costly but it does come in different um dosages per one ampule it's just a little ampule that you just tear off the top and you squeeze the entire amount it's always the first three is always in three ml so a 0.31 milligrams in 3 mls 0.63 milligrams and 3 mls and they have full adult doses 1.25 milligrams and 3 mls now you can get it in a concentrate of 1.25 milligrams per 0.5 ml so all you have to do there um because it's in a half a cc you have to add two and a half cc's of normal saline to get three cc's when you're giving it in the small volume nebulizer i've never seen it in the concentrate i've always seen it in the unit doses where you have three mls and every single little um they're called um a bullet um and and or just a unit dose and it's just in a little ampule um and so it's already premixed for you just rip off the top and you just administer the entire three mls to the patient all right so our long-acting beta adrenergic agents um is a newer trend in the development of non-specific short-acting agents such as epinephrine and our beta 2 specific agents like albuterol but they last longer than the four to six hours and they really do help patients with that nocturnal protection so that they're not waking up in the middle of the night wheezing so in addition to salmeterol for motorola and afromotorole is this extended released tabulate of albuterol and i'm going to talk a little bit more about that so the extended release albuterol is called vospire er er's extended release you get four milligrams or eight milligram or oral tablets um activity time is about eight to twelve hours so it contains two milligrams of the drug in the coating for immediate release and then another two if it's the four milligram in the core for release after several hours and so that could either be two or six milligrams in the core depending on what oral tablet you get our salmeterol is a dry powder inhaler or dpi and so it's not with a small volume nebulizer so our dpis are the ones that are where the patient has to be able to generate 30 to 90 liters per minute of inspiratory flow because it's really not considered a rescue and more of a maintenance it does have a slower onset than our regular albuterol and so we're not going to get peak bronchodilating effect for another three to five hours so again that's why it's not rescue because the patient could really be in big trouble if they had to wait three to five hours for it to work but it will give us about 12 hours of relief for our patients faux motorole is a more specific beta 2 selective agonist it does have a relatively short time to bronchodilatory effect 3 minutes but it's still not considered a rescue it will give us up to 12 hours of relief and it's recommended to get 12 micrograms twice daily it's also in a dpi um they did do some studies and were able to say that it's for asthma patients five years and up or even patients that have exercise induced bronchospasm to help keep that at bay and is also approved for our copd patients that may have that reversibility what's interesting about our long-acting bronchodilators is that they have some anti-inflammatory effects which is a bonus because asthma really does have two major components when it comes to that airflow obstruction number one is the broncho constriction the other piece is this inflammation and when we have asthma that comes from a trigger what happens with these patients is that they have what's called mast cell degranulation and what salmeteron for motorol can do is inhibit mast cell degranulation or mast cell activation whichever one you want to call it so what is a mast cell so a mast cell are mast cells are white blood cells they're considered granulocytes and they are part of the immune system they are produced in bone marrow but when they become activated usually from some sort of outside stimulus so whether it is pet dander or some other type of allergen from dust mites to pollen to um poor air quality all of those things could be triggers for asthma um what happens to the mast cell is it starts to break down from these triggers and when that happens it will release certain mediators and these mediators are actually what are responsible for causing inflammation for example one of the mediators is histamine or leukotrienes and histamine actually has a bronchoconstrictive piece so when histamines are released into the body those those muscles around the bronchials will constrict but what they also find is that these anti these um long actings the salmeteron formoterol prevents an increase in vascular permanent permeability with inflammatory mediators so it doesn't allow some of that histamine to actually get into the lungs like we thought it could and so that has another protective piece that's coming from these long actings but so far we don't have anything that shows that it's clinically proven in people it's just in vitro results only but if even if we're not really measuring it and it's truly happening this is an important piece with our asthma patients that we can reduce the inflammation so our rfo motorol is beta-2 selective might like the formoterol it is a single isomer for motorol so it's a little better than zopanex as a single isomer of albuterol and this one does have quite a bit of success and its duration is up to 12 hours it's available as a nebulizer solution so it's got to go in one of those small volume nebulizers and they did their clinical trials to see if it would work for copd and that's what it's approved for so those copd patients that might have some airflow reversibility not all of them do and the airflow reversibility is minimal it's not a whole lot but at least it provides some relief for our copd patients all right so some of our clinical uses for our lung acting it's again considered a maintenance or control therapy for asthma especially if it's not controlled by inhaled corticosteroids so the corticosteroids is what's going to control the inflammation but it can be used as maintenance when that doesn't work it can be used for copd patients needing daily bronchodilators so instead of always using the rescue they can go to a maintenance one it is not recommended for rescue therapy so patients who start complaining of symptoms the thing they should not be reaching for is their long-acting they all should have a prn as needed albuterol around somewhere an mdi and they should be using that for rescue and not one of the long actings so it's not recommended for breakthrough symptoms as well you still should continue to take it every 12 hours and not take it any more than that so breakthrough symptoms should be treated with albuterol all right i'm just a couple of things to mention about mechanism of action when it comes to the alpha receptor site activation um we do have some agonists or sympathomimetics such as phenylephrine and that is found in some of our nasal decongestants but it also it mimics epinephrine so it's still considered an adrenergic drug and we might be able to see some changes in the patient's bronchoconstriction but phenylephrine is really mostly an alpha um stimulant um and it causes vasoconstriction of the peripheral blood vessels and then our epinephrine of course is oh epinephrine is everything efferent is an alpha receptor activation a beta one a beta two um and and so therefore that's why we're gonna see all the other side effects that come with that as well all right so other things to keep in mind really when it comes to using albuterol um it really is just a specific beta 2 bronchodilator however there are other medicines that can can be be competing for that receptor site um even though it's given maybe for another reason for like the heart for example um some patients may receive what's called a beta blocker and they're exactly that they are antagonistic they are not agonists they block the beta receptor site by looking like epinephrine but it doesn't elicit a response it just holds that spot and it kind of blunts the sympathomimetic pathway so it blunts the sympathetic nervous system and so a beta blocker because we have alpha and beta receptor sites in the heart um by blocking it or being an antagonist it prevents those receptor sites from being stimulated and stimulating them in the heart for a patient that has heart disease can be very problematic so a beta-blocking agent actually can decrease blood pressure and a beta-blocking agent can also reduce the incident of some of our fast heart arrhythmias so a patient that has heart disease does not tolerate a fast arrhythmia because the diseased heart still needs a lot of oxygen and a fast moving heart will reduce the amount of oxygen delivered to the heart and so it doesn't tolerate it well so beta blockers end in o-l-o-l like atenolol and atenolol is an antagonist and it can occupy the beta2 receptor site because it's a little less specific than albuterol so if albuterol is attached to the beta receptor the smooth muscle relaxation can be fully reversed by a beta-blocking agent so it's really just about timing so if we know the patient's going to get a beta blocker hopefully they're going to get it at night right before bedtime because it can cause your blood pressure to drop quite a bit and so we want patients lying in bed and not up and about and so it's a little well it's better tolerated i should say when we take our beta blockers at night so we want to try to plan if the patient needs albuterol on giving it when they're not getting their beta blocker because we really do want that albuterol to work in the sense that we want it to work in bronchodilation we don't want it competing for the um the beta sites by by competing with the beta blocker now what's interesting though um between the short-acting albuterol and the long-acting salmeterol is that when the beta-blocking agent or antagonist is removed so we don't have it it's not it's already been knocked off the receptor site and it's been metabolized and it's gone there's no further relaxation of the smooth muscles so the albuterol doesn't come back in and say hey okay i got this it doesn't work like that so that's why we really have to be careful and not give that albuterol when the patient just got their beta blocker and then salmeterol though um if salmeterol is stimulating the the receptor site um a beta antagonist so a beta blocker would also reverse the effect of relaxation however that salmeterol can still come back later and then go back to that receptor site that beta receptor site and give us the effects that it wants so it stins it tends to stick around a little better and able to be used in that way all right so our roots of administration um can be mdi dpi or nebulized so we nebulizer would be a small volume nebulizer um it can come in or in tablets to be given orally as well as syrup and then we can also do it parentarily and typically that means subcutaneous and that's our epinephrine we're going to give that sub-q so like i mentioned earlier epinephrine is completely ineffective orally so we're never going to see epinephrine tablets but we can see albuterol tablets and they can be given orally but they are less affected if it's better to give it right directly to the targeted organ where we want to get the effects so our benefits of inhalation will give us a more rapid onset because if we give it as a tablet into the belly it's got to be absorbed through the gi tract and then out into the bloodstream and then come back to the lungs at least if we're giving it by inhalation we're going to get it directly to the receptor sites in the lungs and it's a lot more rapid onset we can use smaller doses because we're not having to get past the gut and get into the bloodstream and things like that it does have reduced side effects when we give it just directly to the lungs and so that's giving us that interaction right to the target organ and it's relatively safe and painless that way when we give it by inhaled root so our limitation of the inhalation root is time if you're using a small volume nebulizer that's a good 15 minute treatment so some patients complain that well if i could just take a tablet that would be easier but you're going to have to take more of it if you're going to use it orally than if you're going to use it inhaled and you have the risk of the other side effects some say there's public embarrassment most people are pretty okay with taking their treatments you can take small volume nebulizers with you as long as you have a little compressor that's going to run the compressed gas through the nebulizer and give you that mist that you need on that aerosol production and so you either have to have an electrical outlet or it's got to be battery powered which most of them are not um and some will say it could be difficult to use the the inhaled route correctly and that really is focusing on the mdis there's some timing involved you got to make sure that you're using a spacer and you time the actuation of the drug with when you're ready to take a breath in and so that that timing is there all right we can give albuterol continuously that's a whole lot of albuterol and in some cases when we have an extreme exacerbation of our asthma um we're not going to come like every hour and give them q1 hour treatments what we can do is give them 10 to 15 milligrams in a for an adult 10 to 15 milligrams an hour for an adult remember the normal dose is 2.5 milligrams so that's a whole lot more of albuterol um and now they're leaning towards like up to 30 milligrams per hour of albuterol just depends on how sick the patient is so how do we give a continuous nebulization well we can keep refilling the small volume nebulizer so one small volume nebulizer treatment takes about 15 minutes so once it's done it starts to sputter we just put more in it but that's not exactly um a good use of your time and that's very labor intensive um because you never could walk away you could never go see another patient so what we can do is mix up a whole bunch of albuterol with some normal cell and put it in a large volume nebulizer it's usually about that big and so in our large volume nebulizer we can mix up a whole lot of albuterol and we still run it at the same rate it's the same like eight liters per minute um by doing so then it should have the same output as a small volume nebulizer so we know that we're not giving like 20 milligrams in like three inhalations you know when we're delivering that aerosol it's still going to deliver the same amount of particles in that aerosol generation that's coming from the large nebulizer and it shouldn't be a problem giving anything a whole lot more always runs the risk of developing a toxicity um so we just got to keep monitoring the patient because they can have those side effects including cardiac arrhythmias hypokalemia albuterol is known to reduce potassium it drives actually potassium into the cell and so it causes the patient to be hypokalemic which can actually cause more problems with the heart as well and then because of the glycogenolysis we've got a lot more glucose hanging around and that causes this hyperglycemia and the patient can also have tremors so our oral root does have its advantages it is easy to use it's short administration time they just got to swallow it and there is some reproducibility and control dosages there so we could give a certain amount and we can get the the effects that we want it does take longer to work when we talk about disadvantages and we see more of those systemic side effects because it's got to get through the whole vascular system before it gets to the lungs and then loss due to the first pass through the liver anytime we take anything orally we have that direct route that first pass that can go into liber the liver and things can get metabolized and eliminate eliminated so that is the downside our parenteral route is typically typically typically typically sub-q we can give it by iv but we don't typically do that for bronchodilation now we can give norepinephrine for patients that have other issues and i'm going to get into that in just a minute but the parenteral route for our asthma issues we can give subcutaneously it can also be given for patients that might be experiencing some sort of allergic reaction and we got to give them their subq albuterol so doses are pretty similar 0.3 milligrams or 0.2 5 milligrams when comparing epinephrine to terbutaline and giving that sub-q now for some patients that may have had a cardiac arrest they may use epinephrine as the drug to cause peripheral vasoconstriction so in other words when we have peripheral vasoconstricture so out in the peripheries like on our arms and our legs where we don't have a lot of blood centrally when we have a patient that has a cardiac arrest so they'll give epinephrine so that there's this vasoconstriction so blood is then pushed more centrally not out into the periphery and it also stimulates the heart and can get the heart beating and beating faster if there's a cardiac arrest and then if that's what really is what restores the patient's blood pressure restores their heart rate and all that kind of stuff they can give norepinephrine um slowly through an iv to maintain these things after the code and that's really when you're going to use it that way parentally so this is our long list of side effects a lot of them we've already talked about the tremor the cardiac effects the cns effects the metabolic disturbances because we have a little bit too much glucose going around but we can have a tolerance to the bronchodilator effect if we're misusing the albuterol then it might not work as much and then loss of bronchoprotection meaning that each time we have after using albuterol each time that we have whatever it is the antigen that's causing the effect in the lungs we have less and less ability to protect from that as we continue to use albuterol a little bit more so each time the antigen is actually introduced we're still going to get that effect um a paw a fall i should say in our pao2 so i don't think you've really talked much about that what pao2 is but it's the dissolved oxygen in our blood so when we bring oxygen into our air sacs our alveoli it diffuses through the air saxon is picked up by our bloodstream and taken out into the rest of the body so the partial pressure of that oxygen can be measured in millimeters of mercury and we use to determine whether the patient has a lack of oxygen or normal oxygen level what can happen when we have a bronchoconstriction piece or the asthma piece we can see the blood vessels that are supposed to go to that area when there's less oxygen in the alveoli because of the bronchoconstriction blood gets rerouted elsewhere but when we give the albuterol and the lungs start to open up and what was once constricted now has more airflow to it that blood still takes a while to go back away from where it was deferred you know it was diverted because it our blood will get shunted away from an area in our in our lungs that's not bringing in a lot of oxygen so that diversion is still there and it just takes a while for it to come back and because it takes a while for it to come back to the area that's now getting plenty of oxygen in it um our pao2 value can actually fall and and but it it will fix itself um an mdi has a propellant and the propellant can cause toxicity um and then the patient can have stronger um return of that bronchospasm when they are getting this propellant toxicity um and then the albuterol liquid when it goes into the small volume nebulizer can have an additive and so they can have sensitivity to the additive or even allergic reaction to the additive all right so some will talk about this beta agonist controversy and using it outside of the hospital because some people will use their albuterol and use it and use it and use it and use it and might not go and seek medical help when they really should be getting on other medications to control that that that bronchoconstriction piece also we lose a lot in the translation if we don't do a lot of good education so education is really important and so people may miss an opportunity to take their albuterol and they end up sicker than we'd like them to be so we end up having these compliance issues or they're not getting the right education and then also um we're seeing a little bit more increase in the number and severity of asthma patients and really the biggest thing that has changes our environment um and then of course lifestyle changes so lifestyle changes could include like using more marijuana or vaping or things like that where we're inhaling things that can have an effect on our lungs so that's where we have this controversy of using the beta agonist because we might be still doing things that could be affecting our lungs but if we have the beta agonist then we could kind of like quote unquote fix the problem when we have the problem but we're really not addressing the issue all right we always have to assess our patients when we give a drug is it working do we have the right drug are we doing what we need to do so we really do need to assess the effectiveness um and it's based on the indications of use remember the indication of use was reversibility of airflow obstruction so we have to monitor to see if we see that reversibility happening so we're going to monitor what we call peak flow rates um for our patients that have asthma we should be doing a peak flow before and after the treatment so don't worry about really what that looks like right now but a peak flow is just a device that you take a deep breath and you blow in it really fast and hard and it should measure how much flow we're able to get out of our lungs in that quick little um breath that we do we should see improvement after we give the albuterol so that improvement should be about 20 that should be happening um of course we're going to be doing a physical assessment before and after so we should be seeing or listening to our lung sounds and seeing different changes in the body that shows that the patient's getting that reversibility of airflow obstruction we should make sure that the heart rate doesn't increase more than 20 percent so if we have a patient that's getting albuterol and their heart rate goes up more than 20 we have to stop the treatment we can't continue that because that's just too much of a change in heart rate and then our subjective reaction so what's that that's just asking the patient how do you feel and they say i feel better i feel like i can take a deep breath now or i can get all the air out those are all subjective reactions that are positive and they're feeling better so that's the other thing we should be looking for um we can check the blood that's what an abg is arterial blood gas and all it does is it measures the gases that are dissolved in the blood and the ph of the blood um so an abg tells us whether or not we're getting enough oxygen in and getting rid of enough carbon dioxide that's really all that is and so it's just telling us that we have effectively working lungs and so when we have air flow obstruction though those numbers can fall outside of normal so that's why we will get a blood sample and we will test it for oxygen levels and carbon dioxide levels we should monitor our glucose and our potassium to make sure that the potassium isn't dropping and glucose isn't coming up a pft is just a pulmonary function test so that's going to be more than just that peak flow a pulmonary function test is going to give us a better idea of even lung volumes and whether or not we have air that's trapped inside the lungs because of the airflow obstruction things like that so it gives us a little bit more data it's done in an outpatient setting or it can be done at the bedside with a special spirometer education education education it's so all about education we need to know um when to take our rescue when to continue with our control and maintenance medications when to call the doctor when to go to the er all those things are important so there are education pieces that are important and then when we're doing that education we got to make sure that they can return demonstrations so we have to instruct and verify correct use of devices we have to know that they know how to use them um and how to maintain them and how to clean them and things like that for our long acting our assessment has to be about our ongoing lung function so we should be able to control with our long acting so we should see fewer breakthrough symptoms with these and we should be seeing less symptoms come through at night we need to get the number of exacerbations so how many times did they actually start to feel bad again um and did they use their rescue inhaler when that happened um we should be getting information about whether they've been absent from work or school so that they're sick enough that they're not going to work or school which can really impact their quality of life especially if they miss too much school and they can't pick up where they left off or worse yet with a job and they lose their job that would be bad because they lose their livelihood and their ability to care for themselves and then we need to assess the ability to reduce the dose of inhaled corticosteroids so if we're going to use a lung acting maybe we can come down on the steroids now even though they're inhaled that doesn't mean that they still don't have side effects there are fewer side effects of inhaled corticosteroids and inhaled corticosteroids are far better than giving one by a pill or an iv a systemic one so we're on the right track of doing an inhaled corticosteroid but whenever we can reduce that that's always a good thing so that's what we would should be able to achieve by using a long-acting beta agonist all right one last drug to talk about is that racemic epinephrine it still has a role even though it might not be great for just bronchodilation you know that beta-2 specificity that we're not going to see from this synthetic epinephrine but it's a really great vasoconstrictor so we can use it when we know that there's bleeding going on so we have a special scope that can go into the lungs and we can actually visualize the the bleeding and we can put a little bit of racemic epinephrine down there it's going to cause that vasoconstriction and when we have vasoconstriction then we have a decrease in swell decrease in bleeding we're going to use it to reduce airway swelling and we've got a couple of things that can cause just swelling right here in the upper airway not so much in the bronchioles so when we pull the breathing tube out of their lungs the area around the vocal cords can have swelling so racemic epinephrine is great for post extubation strider so stridor is an inspiratory sound that comes from swelling in the airway epiglottitis and croup are two different diseases mostly childhood diseases that affect the upper airway we do have a vaccine for epiglottitis but we're starting to see um a little bit more um increases in incidence of epiglottitis because of the anti-vaxxers out there um and so epicotitis is caused by hemophilia hemophilus influenzae h flu and then croup is called spi parafluenza and so paraflu is the sister virus to our influenza a influenza b our irregular seasonal flu and croup tends to settle in just the upper airway of small kids and because their airway is smaller it causes them to narrow a little bit more and gives us that strider sound again from air just moving in the upper airway through a narrowed opening and then bronchiolitis is typically found in children less than two years of age and it's seasonal it's typically caused by a a virus called the respiratory syncytial virus or rsv and it get it too can cause swelling in the upper airway and can cause that stridorous sound and in that case we would re we would use racemic epinephrine for that it's a little bit better for reducing swelling than it is for bronchodilation and again it has that strong alpha adrenergic vasoconstricting effect and that's why it's really great at reducing swelling because we've got vasoconstriction not a lot of blood going to the area and it's naturally just going to cause the swelling to go down all right this clinical scenario we're going to wait we're going to talk about this in class um and so if you have any questions you know how to reach me rebecca.hanley gccd.edu have a good rest of your day