Autonomic Pharmacology | Muscarinic Antagonists

what's up ninja nerds in this video today we are going to be talking about anti-muscarinic agents these are some really cool agents and we'll get to talking about these in just a little bit but before we get started what i want you guys to do is if you guys like this video you benefit from it please hit that like button comment down in the comment section and please subscribe also if you want some great notes and illustrations to follow along with me during this lecture which i really think will help you go down the description box below we'll have a link to our website where you guys can check all that stuff out all right engineers let's get right into it so first things first in order to understand these kind of anti-cholinergic drugs and really we're putting this anti-cholinergic category into what's called the anti-muscarinic types of agents we have to understand the basic physiology of the parasympathetic nervous system right because these drugs if you want to think about if they're antagonizing that type of muscarinic receptors then they're kind of trying to work like a parasympatholytic if you will right they're trying to oppose the parasympathetic nervous system so let's kind of briefly go through this physiology so when we talk about this there is what's called acetylcholine releasing neurons and muscarinic receptors and nicotinic receptors present within the central nervous system but what do they do what is their function because what we're going to talk about is we're going to try to inhibit that that's the basic concept of all these drugs so the basic concept if we were to zoom in here and look at some of these acetylcholi releasing neurons are areas of the brain that are involved in acetylcholine releasing muscarinic receptors we get into the area first of the basal ganglia so we have our basal ganglia and you guys know a little bit about the basal ganglia and how it's involved in a lot of our movement processes right so the basic concept here is it's involved in regulating movement and this movement if you will is really controlled or mediated by a balance between dopamine and acetylcholine so if i were to draw like this kind of like little seesaw let's say here this seesaw is kind of really kind of keeping a balance of movement and really is regulated by two particular agents on each side one is your dopamine the other one is the acetylcholine now what we need to understand is in certain diseases we have alterations in this particular pathway which alters the patient's movement so it is involved in the modulation of movement the other thing that the acetylcholine releasing neurons are muscarinic receptors are present because we're giving drugs that are blocking acetylcholine at the muscarinic receptors right there is a lot of muscarinic receptors in this little special center in the brainstem near the medulla and this structure here is called the ammetic center or the vomiting center and all that means is it controls our vomiting response and there's a lot of things that trigger vomiting right this could be due to vestibular dysfunction so a lot of like disequilibrium it could be due to stretching or distension or irritation of particular factors within the git or it can be higher level functioning that's driving this there's a lot of things that can trigger this imesis but the actual receptors are located on that center in the brainstem so that's the basic i want you to understand here now next thing is we also have muscarinic receptors that are present on the actual eye now on the eye you have different types of tissues here on the eye you have the muscles here for the pupils and then you also have muscles which are involved with what's called the ciliaris and the basic function here of this particular pathway is it generally wants to cause what was the parasympathetic want to do does it really normally want to cause pupil constriction or pupil dilation naturally it wants to cause pupil constriction so the natural type of mechanism here is it wants to cause the pupils to undergo constriction and then the other thing here is it also wants the ciliaris to be able to contract and when the ciliaris contracts this actually helps to be able to play a role and when it contracts it pulls open the angle where the aqueous humor drains so it increases the aqueous humor drainage and also it can play a role in accommodation of the actual lens so it also can accommodate the lens for different changes in vision all right so that's the basic concept there so we know central nervous system the way it's actually mediating it here in the cns is it's mediating this via movement via the basal ganglia and vomiting via the immediate center of the medulla it also works in the eye to cause pupil constriction and ciliaris contraction causing aqueous humor drainage and accommodation the other thing is it can also act oh real quick what is the actual parasympathetic fiber the parasympathetic nerve here that works on the eyeball this is going to be the third cranial nerve where we have other nerves of the parasympathetic nervous system that innervate the glands this could be what are the glands here the lacrimal glands this could be the lacrimal glands and it can also innervate the salivary glands and so obviously it's not too hard to imagine what these will do if they're stimulated when they're stimulated by acetylcholine acting on the muscarinic receptors in these areas they're going to cause not too hard to imagine here lacrimation so they'll increase the tear production and they'll also increase salivation and so this may cause a lot of oral secretions to be formed right and the basic concept behind this is that the parasympathetic is involved in the resting and digesting phases okay the next thing it also and again what's the actual cranial nerves that involve with this process this could actually be a couple this could be the facial nerve and it can also be the glossopharyngeal nerve so this would be cranial nerve seven and also we can see this with cranial nerve nine which is the glossopharyngeal nerve now the next one is the big boy the vag bond this is the vagus nerve the wandering nerve this one is the parasympathetic nerve that supplies a bunch of different types of viscera that are involved in our parasympathetic nervous system works on the heart releases acetylcholine on the muscarinic receptors of our heart particularly our nodal system you know you have the sa node and then the big one the av node bundle of his bundle branches all that stuff right it's going to particularly work on these bundle systems and then the av node sa node to slow down the heart rate and it also wants to slow down the cardiac output because you want to conserve the amount of energy that the heart is actually going to be pumping and utilizing during a resting and digesting phase so the other thing here is it works particularly on the bronchioles right the smooth muscle of the bronchials and whenever it works on the smooth muscle of the bronchials what it's actually going to do is it's going to induce what's called a bronchoconstriction so maybe able to do bronchoconstriction because usually whenever your bronchials are constricted or a little bit more tight you're not going to have to be able to involve too much with airway movement when you're resting and digesting so we don't want to utilize a lot of energy here so it actually will cause some degree of bronchoconstriction all right so i really want you to remember these things because this basic physiology all we're going to do whenever we get into the anti-muscarinic agents is we're just going to flip it we're going to have all of these things doing the opposite of what we're talking about here okay the next thing that we want to talk about here is how it also works on the liver now this is not a huge one but the liver it actually can increase bile release which is involved in digestion and it can also cause the smooth muscle of the git here to increase motility and it also can work on some of the glandular tissues involved in here to increase secretions that are involved in digestion so it can increase secretions it can increase motility these are huge features that i want you guys remember for the git the other thing here is that it's really interesting like the sympathetic nervous system right is involved in potentially the patient being able to sweat so but the interesting thing here is that there is muscarinic receptors so the sympathetic nerves are the ones that are actually going and innervating the glands involved in sweating but the neurotransmitter that's released is acetylcholine and then there's even some muscarinic receptors here so it's interesting because this may even be involved in kind of a sweating type of response so it may cause sweating so you can see how some of these things are really going to play in whenever we talk about this stuff a little bit later it's really going to be cool we're going to make it all make sense so we got the cranial nerves here we got the sympathetic nerves which are really supplying the sweat glands involved in the skin but there is some acetylcholine being released here and some muscarinic receptors here that are involved in the sweating process so we can technically include this here there's also the sacral nerves so s2 3 and 4 which are also involved so these are parasympathetic fibers that are going to be supplying some of the lower aspects of our abdomen and pelvis so it'll go to the the actual bladder and it'll cause bladder contractions and if it causes the bladder to be able to contract it really contracts that detritus muscle it can lead to urination and then it also can act on the lower parts of the git so usually the vagus will go all the way up until you get to about the transverse colon about half way through the transverse colon and then the sacral nerves from s2 3 and 4 will supply like kind of like halfway from the transverse colon all the way down to descending sigmoid colon etc but it also is going to be involved in increase and the gi motility so you guys can see here how the a lot of this stuff has come into play and what i really want to outline now as if we come back up is i want you to understand now if we were to give a drug that's going to oppose this so we're going to give a drug that's going to act at the muscaritic receptor and we'll show you that mechanism in a little bit it's going to bind onto the muscarinic receptor and block acetylcholine from being able to work on that receptor and initiate its effect so it's going to oppose all these actions so it'll play a role in altering movement potentially if you have some type of disease processes here that can be a problem it can potentially cause some prominent problems with vomiting but here's where i really want to get into it if you're going to oppose this what would it do it would cause pupil dilation it's going to cause the ciliaries to knock a track which is going to increase the aqueous humor accumulation it's going to cause decreased lacrimation decrease salivation it's going to increase your heart rate increase your cardiac output it's going to bronchodilate it's also going to decrease bile secretions which are involved in digestion it's going to decrease gi motility which can lead to constipation it's going to cause less sweating which can cause your body temperature to go up and it's going to cause less bladder contractions meaning that you're not going to urinate you're going to retain and again less gi motility not going to be able to defecate maybe develop constipation so you can see how a lot of these things are really really important to understand the basic fizz so now what i want to do is i want to go over a basic kind of concept about how these drugs work at the muscarinic receptors briefly talk about muscarinic receptors and then go through the drugs and how they work on this particular diagram here all right my friends so now we're going to talk about the muscarinic antagonists the actual types of drugs but also just briefly kind of go over how they work at the receptor site just that you understand right so we were kind of looking at all the nerves that were going to that ganglion right so they were you had potentially going to your postganglionic neuron where they were synapsing so you had that synapse point and then you had the postganglionic neuron going all the way to the target organ well now we're going to do is we're just going to talk about okay we act on the target organ we talked about all the target organs that could be affected the eyes we talked about the glands we talked about the heart the lungs the git the bladder the skin all of that well really how this happens though is it's happening between acetylcholine and the muscarinic receptor so you have these receptors these muscarinic receptors and really what they are they're g protein coupled receptors right so there's different categories and so in this one here i want to talk about what's called the m2 receptor and then another one called the m4 receptor and the reason why i want to group these receptors collectively is that these receptors primarily are going to be inhibitory types of receptors so they're trying to be able to perform inhibitory functions what what do i mean the really the primary organ i think is that is the best example in this situation is the heart so if you guys remember all of them they were trying to increase motility salivation etc in this situation for the heart it's decreasing it's slowing down something and the basic mechanism here is that when acetylcholine is being released from this postganglionic neuron it needs to bind on to this muscarinic receptor so here is your muscarinic receptor and when it binds onto the muscarinic receptor it activates kind of an intracellular pathway and the basic concept here is it decreases cyclic amp and it also causes two things one it decreases cyclic amp and it also causes potassium ions to be effluxed out of the cells and so you kind of get a double whammy here where you get less cyclic amp and less protein kinases that are activated they're involved in all the phosphorylation reactions but also you get an increase in the potassium leaving these cells which kind of makes the cell become hyper hyperpolarized and less active that's why in patients who this action on the heart what does it do it slows it down it decreases the heart rate and subsequently drops the cardiac output you don't really see that in a lot of the other target organs so oftentimes the m2 m4 receptors are primarily your g-inhibitory type of g-protein-coupled receptor so these are primarily coupled with what's called a g-inhibitory protein they decrease cyclic amp decrease protein kinases and cause potassium ion efflux in the other situation here where you have this neuron it's releasing acetylcholine this acetylcholine is binding onto this muscarinic receptor and what it does here is it increases the cyclic amp it increases the protein kinase which phosphorylates a bunch of proteins that increase cellular activity of some way shape or form and if you increase protein kinases what you'll see as a result of this is an increase in particular types of contractions secretions etc and so for these it's usually all the other receptors so this is your m1 m3 and m5 receptors so generally these receptors are usually coupled in some way shape or form to like a g stimulatory or gq protein they're more of a stimulatory type of receptor okay so usually for the most part they may be coupled with what's called a g stimulatory or a gq protein either way they're trying to increase the activation of enzymes to cause contraction so this would be i think the best example that i can think of here would be the bladder so if you think about the bladder what does it do to the bladder it causes an increase in the contractility of the detruster muscle to cause urination so that would be kind of a factor here or on the git where it causes an increase in contractility increase in secretions the glands increasing salivary secretions increasing lackable secretions you get the point here so it's important to be able to remember that this primary mechanism of action here is to be able to increase you know in this case urination so i hope that makes sense what we're doing when we give these muscarinic antagonists is we're giving a drug here that i'm going to use in red that's going to work here to block this reaction so this muscarinic antagonist is actually going to come here and block this reaction therefore blunting the inhibitory effect and blunting the stimulatory effect in this kind of muscarinic categories so really try to be able to understand this basic concept if you're a little confused go watch our video where we talk about all the cholinergic receptors in our physiology playlist there all right but let's get into some of these muscarinic antagonists that are doing these types of opposing functions the first one here is atropine so atropine is a really interesting drug what it does is it blocks the muscarinic receptors present with on the pupil and the muscarinic receptors in the ciliaris and when it does that it actually blocks those particular receptors here what's it going to do what did it normally do normally it causes pupil constriction we're going to oppose that you see why i told you to remember this it's going to cause pupil dilation why is that important if you're trying to perform an eye exam on a patient and you want to be able to look at the retina or for whatever reason you may need to allow for people dilation it also will decrease the drainage into that canal schlem because remember the ciliaris doesn't contract so one of the big things to watch out for here is that it can cause a change in your vision right so it can affect the ciliaris so the ciliaris actually becomes inhibited in this situation and this may affect the accommodation which may cause some blurry vision but on top of that it may affect the drainage of the aqueous humor which can increase intraocular pressure so you probably want to be careful of this with patients who have glaucoma narrow angle glaucoma this could worsen it the other thing here is it acts on the glands right now what do these glands normally want to do when the acetylcholine acts on these muscarinic receptors they want to secrete so for the most part most of these are going to be m3 receptors for the most part so they're all going to cause a pupil dilation and this you're going to generally inhibit them from causing constriction and contraction so in this situation you're going to pupil dilate and inhibit the celiac contraction in this situation you're going to decrease the secretions so in this particular scenario you'd see that the patient would have decreased lacrimation this may dry out their eyes you also will decrease the salivation and this is an interesting type of thing here why would you want to do this you would want to do this in situations where patients have like a lot of drooling maybe they drew a lot or sometimes they use this pre-intubation or perioperatively to kind of clear up the patient's secretions when you put the tube in so there's not a lot of secretions that are going to affect them while they're intubated so sometimes it can be done pre-op or we can say versus pre-intubation basically to kind of clear up some of those upper airway secretions to get them out of the way during the intubation the next thing is if we come down here it can act on the heart right now think about this these were like your m3 receptors up here that you were antagonizing what's this one going to be an m2 receptor so in this situation you're acting to again oppose the m2 receptor present on the av node and sa node so in this situation they naturally want to decrease your heart rate decrease your cardiac output what do you do increase your heart rate increase your cardiac output so watch out for these patients to potentially have an increase in heart rate and increase in cardiac output why in the heck would you use this you would do this if the patient has severe bradycardia so if they have a severely low heart rate for some particular region you can quickly it's kind of one of the first line medications to give in symptomatic bradycardia so i would potentially give this medication so do you guys remember the particular drugs that we talked about just recently the cholinergic agonists particularly the anticholinesterase so the cholinergic agonists and these are particularly the anticholinesterases and they were working potentially to cause some type of what we would potentially refer to as a cholinergic crisis and we talked about how to differentiate this from someone who has like myasthenia crisis right we can give atropine to treat as an antidote in patients who have a cholinergic crisis due to increased cholinergic agonist type of use so i would consider this as a antidote potentially in a cholinergic crisis okay let's move on to the next drug so we got atropine now we get this next one called scopolamines kapolem is a really interesting drug you use it a lot preoperatively postoperatively sometimes if you're going out and getting on a boat for the first time and you get a little bit of motion sickness the basic concept here is that if you guys remember i told you we'd come back to this a little bit later is that this area is called the ammetic center in the medulla right so it's called the ammetic center and the basic function here is that whenever there is this a medic center it's involved in vomiting now remember what i'm telling you is that generally whenever there is a lot of this acetylcholine acting on these muscarinic receptors whether it's an m1 m3 m5 it's trying to stimulate vomiting okay in that situation i want to give a drug that blocks these muscarinic receptors on the ammetic center blunting the vomiting reflex so what would scopolamine do it would inhibit the vomiting type of process when would we want to inhibit vomiting the two situations here is we would want to do this in patients who have some type of motion sickness because especially from that vestibular dysfunction this can really over activate that medic center so motion sickness tends to be a really really good one and i'm going to abbreviate this because it's commonly abbreviated is post-operative nausea and vomiting from like the anesthesia and opioids and things of that nature okay so that's a really cool kind of thing there all right the next one here is called binge trapine and trihaxyfanadil so again i told you i'd come back to the medic center stuff and i told you i come back to the cns stuff with the basal ganglia i want you to understand it here so these drugs are really interesting remember i told you i used this kind of like balance beam if you will where we have there's a degree of movement right so movement if you will is modulated by the balance between two particular neurotransmitters in the cns and this is dopamine i'm just going to put dopa and then acetylcholine in disease states where you have a massive reduction in dopamine now acetylcholine may be overpowering throwing off the maintenance and the kind of nice equilibrium of movement and what kind of diseases would this now happen where now i have since this is kind of going down now acetylcholine unfortunately is going to have to go up what kind of drugs could i do or what kind of drugs actually potentially would decrease dopamine and cause this imbalance and that would be a potential indication for bench-tripping or trihaxyfenodyl or what kind of disease decreases dopamine release and cause this inadequate increase in acetylcholine pathways come on i know you know which dopamine is really important because it's released from this structure called the substantia what kind of disease destroys the substantia and then drops your dopamine release within the basal ganglia parkinson's disease so we can utilize this in parkinson's disease my friends parkin sends disease and this may be helpful particularly within the tremor component so we might be able to reduce some of the tremors associated with this disease okay particularly by affecting this pathway what you're trying to do is the acetylcholine levels are too high acting on those muscarinic receptors what are you trying to do inhibit this excessive kind of inadequacy between dopamine and acetylcholine you're trying to level this back out but since dopamine dropped down you don't want this acetylcholine working too much so you want to inhibit some of the acetylcholine to try to reset that balance so that could be one disease what's another disease that actually doesn't destroy these but maybe when dopamine is being released and it's acting on some of these receptors involved in various different pathways pathways of the body i give a drug hmm i give a drug that will basically work too oppose this sometimes we use this in patients unfortunately because they are a little bit delirious they have some type of psychiatric disorder but what it's going to do is it's going to try to reduce the dopamine levels you guys know what these are antipsychotics so antipsychotics may also produce this interesting type of effect so anti psychotics especially in like higher doses what can they produce extra pyramidal symptoms they can alter the dopamine dopamine and acetylcholine balance and if they cause extra pyramidal symptoms like akathisia and different types of similarities between the parkinson's disease parkinsonian-like symptoms what would we want to do we want to give them this particular drug to alleviate the extrapyramidal symptoms caused by antipsychotics which alter this equilibrium between these two neurotransmitters all right that covers this drug category now let's move over here and talk about these other two drug categories all right so next one is this drug category of oxybutynin tulteridine and sulfenasan now these are interesting so we've got atropine we've covered that one scopolamine benchtropine trihexy phenotyl and now we've got these other ones called oxybutene and tiltoridine sulfenosine probably commonly utilized one as oxybutynin so it's really kind of straightforward to think about how this works right naturally whenever acetylcholine works on muscarinic receptors in the bladder what do they want to do cause bladder contraction if they want to cause bladder contraction that's going to induce urination what if a patient already has too much urination they're urinating undesirably so they have urinary incontinence so generally in this process here what do we know is that this bladder if it's under the effect of acetylcholine by the muscarinic type 3 receptors in this situation what will it do it'll increase the bladder contraction and if you increase the bladder contraction you'll increase urination so what if the patient has a particular disease that you want to inhibit that so now what i want to do is i want to give these drugs because what they're going to do is they're going to inhibit this process here this would be in situations such as urinary incontinence or um like urgency right so think about all those different cases and i think one of the really big ones here is like overactive bladder that tends to be a really really big one to also think about here so i think it's a pretty straightforward one not too crazy right the next one is this next drug category i was kind of potentially not going to mention but i think it's something to think about dicyclamine and hyaciamine we sometimes can use this because if you think about it what is the acetylcholine act on the muscarinic type 3 receptors present on the git what are they going to do they're going to try to cause increased genomity and increase gi secretions so if a patient has let's say increase in their gi motility and that potentially causes an increase in movement maybe maybe some diarrhea what if the patient already has a disease or maybe they have a lot of diarrhea or if you increase their gm motility this may cause sometimes it really can it can cause spasms within their git what if i wanted to give these drugs to inhibit this process because they have too much spasms and too much diarrhea there's one particular condition called ibs so right ibs is going to be irritable bowel syndrome there's two phenotypes if you will one is there's ibs c so in basically irritable bowel syndrome where they have more predominantly constipation or ibs d so irritable bowel syndrome where they have more predominant diarrhea i would probably find some benefit to give this to a patient who has ibs d why because what i'm going to be doing is reducing some of the spasm associated with this increased gym motility that they see in this disease and inhibit some of the diarrhea that they see within this potential disease so remember this potentially in ibs d predominant all right so let's come up here and talk about tertiary means but before we talk about um tertiary means i want to quickly quickly um understand why did we discuss the difference here so we finished talking about tertiary means we're gonna move on to quaternary means why did i categorize them like this there's a particular reason okay if you remember we talked about scopolamine and benchtropine and trihaxyfinidal do you see how these ones penetrate across the central nervous system there's a reason why tertiary amines are lipophilic and because they are very lipophilic it's easier for these to cross the blood brain barrier and then have effects upon the central nervous system drugs which are quaternary amines these are hydrophilic and therefore have a difficulty being able to penetrate across the blood-brain barrier and affect the central nervous system that's a really big point that's kind of why i wanted to really kind of separate these two in that way but now that we've covered the tertiary amines and the reason why i wanted to do this because scopolamine and bench-tripping and trioxide will definitely have a lot of cns penetration we're going to talk about these two categories here within quaternary means the hydrophilic less cns penetration more peripheral organ involvement glycoparalate is actually a really interesting drug sometimes i'll actually use this drug a lot and patients who have a lot of drooling so sometimes patients may have cerebral palsy they have certain types of like psychiatric disorders that may cause excessive amounts of drooling and so what glycopyralate will do is we'll think about what does naturally the muscarinic 3 separate receptors present on these glands going to do increase secretions and if you increase secretions present within the oral and upper airway this can be somewhat problematic right because it may cause increases in drooling or it may cause increased respiratory secretions that can kind of clog up the endotracheal tube make it difficult to be able to manage it maybe cause some pneumonia things of that nature so glycopyralate is going to work to be able to inhibit this increase in secretions kind of clearing up the drooling and removing some of these respiratory secretions and the reason why this may be helpful is again same way we talk about atropine may be using this as a pre-op kind of situation or a pre-intubation and a way to clear up some of those respiratory secretions before the tube goes in okay so that's glycopyrulate the next one here is iprotropium and tiotropium bromide these are actually really cool drugs so again we know that when we talk about what this does to the airway there's actually muscarinic types receptors here present on the smooth muscle and the muscarinic receptors here present on the smooth muscle of the bronchials what are they going to actually do they're going to try to be able to promote what type of effect here whenever acetylcholine binds acetylcholine will provide a broncho what constriction so it's going to act on these muscarinic 3 receptors and cause an increase in bronchoconstriction and that can cause difficulty being able to ventilate air in and out especially in what kind of diseases and diseases such as copd and diseases such as asthma where they have problems with bronchoconstriction what if i gave iprotrophium entitium to be able to inhibit this bronchoconstriction process if i inhibit the bronchoconstriction i'm going to allow for better air movement in and out of the lungs in situations such as copd and asthma the question that you may have though is what's the difference between ipotropion timotropium maybe you didn't have a question about that i think it's relatively important to remember is that sometimes what's really kind of relevant here is that iprotropium is actually going to be more short acting so sometimes we call this what's called a short acting muscarinic antagonist right whereas tyotroprium is going to be more long-acting thus we call this a long-acting muscarinic antagonist relatively important to understand that especially in the copd and asthma videos that we've talked about all right my friends that covers the cholinergic physiology that covers the muscarinic antagonist now the problem is what if a patient takes maybe too much of these muscarinic antagonists they get a little bit of a belladonna poisoning we'll talk about that or they take other medications that have anticholinergic properties and they develop some really nasty adverse effects like anticholinergic toxicity what do we do then all right so anticholinergic toxicity we'll talk about the causes but the basic causes i'll just hit with hit it with you right now but then we'll space our repetition a little bit later it's basically you take too much of these drugs you take too much of an antimuscarinic agent or you know tricyclic antidepressants they have anticholinergic properties within them they can also cause this as well if you take too much of them the other ones could be antipsychotics and then the last one could be first generation antihistamines and the last one i i don't even know where you find i'll show you guys a picture of but a belladonna plant particularly the the berries and the leaves potentially from that plant may have a lot of these antimuscarinic types of anticholinergic properties that could cause anticholinergic toxicity um but the basic concept is just again in this situation we're really dropping down the action so everything that we talked about before with the cholinergic physiology amped us down even more so drop down so let's see if you guys can remember this for the cns it played a role particularly within movement but it also plays a role within our degree of like just basic cognition in these patients whenever they have this incent and insane types of anti-muscarinic types of blocking you get an intense change within their cognition and it can even cause these patients to become extremely delirious so it can cause delirium it can cause an intense alter mental status rarely but possibly maybe even seizures okay the other thing is again it's going to cause massive pupillary dilation so massive pupil dilation and it also again is going to cause potentially a blurry type of vision this could be because of the pupil dilation but it also could be because the ciliaris is not going to be contracting right it's not going to play a role within that again it's going to change the shape of the lens to accommodate it for more of a particularly like more of a potential change for near vision so it causes a lot of blurry vision the other situation here is it's going to affect the glands so it's going to cause intense dry eyes and intense dry mouth so watch out for dry eyes dry mouth it's also going to again oppose the parasympathetic effect on the heart which is to decrease heart rate so it'll actually cause massive increase in heart rate so potential tachycardia and it may increase the cardiac output enough that it causes hypertension an increase in blood pressure it also may cause pretty decent bronchodilation which may sound really good okay and then also here it gets a little bit more interesting remember i told you the sympathetic nervous system particularly from like your t1 all the way down to l2 the sympathetic fibers supply the sweat glands right but the actual neurotransmitters that may be released at this point here is going to be maybe some acetylcholine and there might be some muscarinic receptors present here so if i give an anti-muscarinic agent what naturally happens with this pathway is to induce sweating if i inhibit this i will cause very very very little sweating so i'm not going to be able to cool my body down at all via evaporative cooling and this may cause the body temperature to shoot up to the point where the patient can develop hyperthermia okay so watch for very very high temps in these patients the other thing is that you're not gonna be able to poo so you're not gonna be able to restock the lake with brown trout right and that's a problem if you can't make the brown pickle what are you gonna do you're gonna have severe constipation so these patients won't be able to offer adequate contractions of their gi tea so they can develop severe constipation that's a thing to potentially consider here i would probably be careful giving this drug in situations such as maybe maybe i would actually potentially consider this i would not give this medication or i would avoid giving these medications and what types of scenarios a small bowel obstruction a large bowel obstruction an ileus of some type where the bowels aren't already moving because then you put this patient at risk of a perforation if they can't contract their git pressure can build up and they can perf so potentially avoid that right the other thing here is that it can act on the bladder naturally we want to cause bladder contractions but if we can't cause bladder contractions because we're going to oppose this what's it going to cause severe retention and this retention can be a problem right so i would also be very careful and avoid maybe this medication some patients who already have issues with retention and especially in situations where they have like some type of bph where they already have retention maybe avoid that as well and that brings me to this other conversation here one of the really really big ones here is remember i told you it changes the it causes the ciliaris naturally to contract but if we inhibit that it won't be able to contract it won't be able to change the shape of the lens it won't be able to open up that angle for aqueous humor to drain and so because of that you'd really want to avoid some of these drugs and what other situations such as diseases that have a high intraocular pressure such as glaucoma especially narrow angle glaucoma so important contraindications that i wanted to just disperse in there with these antimuscarinic agents really trying to avoid them in situations where patients already have problem with their bowels problems with their bladder are problems with their eyes but let's get back to the problem at hand here some of the key features is delirium right alter mental status seizures blurry vision pupillary dilation so look for big big honking pupils dry eyes dry mouth tachycardia hypertension don't worry about this one hyperthermia constipation and urinary retention what i told you again as a spaced repetition is obviously causes here if we were to go through them it's going to be all of these anti-muscarinic agents that we just discussed if you take too much of this that could be one reason the second reason that i would also consider these is drugs that have anticholinergic properties tricyclic antidepressants or what else antipsychotics are also going to be drugs that have these types of anticholinergic properties the other ones are going to be first generation antihistamines these also have anticholinergic properties and the last one here is that belladonna poisoning they may ask you this one on the exam or they may present it in the clinical vignette so belladonna plant poisonings and we'll show you guys a picture of what that looks like but i think the big thing is you have this within the clinical vignette that you had too much of these or maybe you intermingled that's another thing maybe you took one of these with this or you mixed an antipsychotic with an antimuscarinic either way you mixed drugs that had extra or additional anticholinergic activity and you just had too much anticholinergic activity here that it causes these problematic issues and then the last thing here is if we have a patient who has evidence of anticholinergic toxicity right because they took one of these medications too much of them or they intermingled a bunch of them and they start developing these effects what can we give them the one particular drug that may be of benefit here is going to be physo stigmine this is one of those cholinergic agonists so it's going to basically do everything opposite of what the anticholinergic types of toxicity presentation is so this may be a potential drug to consider as an antidote in this situation but oftentimes it's supportive care and allowing for the drug to be metabolized on its own all right my friends let's do some questions here on muscarinic antagonist so the first one here that we're going to start off with here we go some sarin gas all right so sarin is a nerve gas that is an organophosphate it's a cholinesterase inhibitor all right and we talked about that one it's one of those irreversible types really nasty one so which agent could be used as an antidote to a cholinesterase inhibitor so in a patient who has a cholinesterase inhibitor it's going to increase the acetylcholine in the synapses which can lead to a cholinergic crisis which one of these drugs can be given in a situation of a cholinergic crisis because what it's going to do is it's going to help to potentially block the effect of the acetylcholine at the different types of muscarinic receptors so in this situation which would be the best drug of choice here my friends it would be atropine we already know that atropine is going to be the particular treatment of choice in a cholinergic crisis so it would be atropine all right the next situation here is a patient with asthma was prescribed a beta 2 agonist for the acute relief of bronchospasm but did not respond to the treatment which drug is most likely next option for this particular patient alright so when we look at this a patient with asthma was prescribed a beta two agonist now beta two agonists are supposed to work on the bronchial smooth muscle and to do what they're supposed to cause bronchodilation but they didn't respond to it okay so if you gave them a beta agonist they didn't improve oftentimes what you may do next is either bump up to the next particular thing and so in this situation one of the other drugs that is actually kind of interesting that's a muscarinic antagonist that works against the m3 receptors that are present in the bronchial smooth muscle that also causes bronchodilation is iprotropium so remember epitropium or tyrotropium issues epitropia is more for the short acting entire tropium is more for the long acting like once or twice daily kind of situations so it would be epitropin because again it's blocking those muscarinic receptors that also play a role within bronchodilation all right a 50 year old male who is non-complying with medications was recently diagnosed with copd his physician would like to prescribe an inhaled anticholinergic blocking the m3 receptors that is dosed once or twice daily which drug is most appropriate for this patient so the iprotropium is more for acute exacerbations prn kind of situation for chronic kind of daily management long term once or twice daily that's going to be the long acting so that would be your tiotropium or your lama so in this situation it should be tiotropium all right which is the most effective drug for motion sickness for a person planning to go on a cruise remember the vestibular function is connected to the structure called the ammetic center which is present in the medulla that has lots of muscarinic receptors present on it and if we give a particular drug that can block those muscarinic receptors on the medicine and the medulla it may inhibit the vomiting response due to vestibular dysfunction and that drug is scopolamine all right last question here it looks like so which drug is actually the most useful in treating sinus bradycardia i think the best thing to think about is when a patient has bradycardia usually if we want to think about this it's usually due to the vagus nerve that could be releasing too much acetylcholine and if it's releasing too much acetylcholine onto the av node it's inhibiting the av node from conducting at conducting action potentials effectively which slows down the heart rate so if we give a drug that will block the acetylcholine on the m2 receptors on the heart it may be able to prevent the av node inhibition and blocking and then allow for the heart rate to go up and the best drug for that is going to be atropine all right my friends that covers this case study on muscarinic antagonist i hope it made sense i hope that you guys enjoyed it and as always until next time [Music] you

Channel: Ninja Nerd

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Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science

Id: E7TGcvd_Tak

Length: 44min 4sec (2644 seconds)

Published: Fri Sep 16 2022