14.07 Parasympathomimetics (Cholinergics)

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So, in this video, we gonna talk about the parasympathomimetic medications. I wanna go over some more information about the autonomic nervous system before we start these drugs. We also did review this information in detail in the video called ‘autonimic nervous system.’ But, I’m just putting this information here so it helps to understand these autonomous nervous system drug classes because they are the really hard one as far as understanding and remembering too. So, this is the, all the action by sympathetic nervous system. I’m not gonna go into each one detail and this is the parasympathetic nervous system, if you want to understand in more detail, watch autonomic nervous system video.So, the parasympathetic. Since, we gonna talk about the parasympathomimetic drugs in this video, this is an overview of parasympathetic system saying the minor transmitter in the parasympathetic nervous system is acetylcholine.Parasympathetic nervous system has two main receptors; Muscaranic receptors and Nicotinic receptors. Muscaranic receptors are located into the heart and all targeted parasympathetic organs such as liver, kidneys, respiratory and all the organs. While the nicotinic receptors are located in to smooth muscles specifically not any other organs, just the smooth muscles. Now, let’s talk about the parasympathetic nervous system. So, if you go back to the first slide, whenever you give a drug that goes to the parasympathetic nervous system receptors and binds it, and activates the parasympathetic nervous system, it’s gonna cause all these effect on our body. Like, decrease in heart rate, bronchial muscle contraction, arteries relaxation, salivary gland gonna increase the salivation, GI tract muscle walls contraction, GI tract sphincters gonna relax, urinary bladder is gonna contract, and all other actions. So, keep in mind when we talk about these drugs.Parasympathetic medication. There are two different types of parasympathomimetic which we gonna cover in this one, and parasympatholytic. This one is also called cholinergic, while this one also called as anticholinergic. There are two different classes in parasympathomimetic which is indirectly acting and directly acting. So, let’s talk about the direct acting first, this one, direct acting parasympathomimetic and indirectly acting parasympathomimetic.So, Direct Acting Parasympathomimetic drugs is similar to the acetylcholine neurotransmitter which is the main neurotransmitter for the parasympathetic nervous system. So, what they will do, this direct acting parasympathomimetic drug, they will go and bind to the muscaranic receptor of the parasympathetic nervous system and will cause its effects. So, whenever they bind to this muscaranic receptors, it’s gonna cause all the effects caused by the parasympathetic nervous system. They are mostly used for the ophthalmic agents and to increase the bladder tone. Because if you remember, this medication will contract the urinary bladder and this one will cause, this one is also used for the ophthalmic agents. So, let’s talk about the each one. Because in this class, if you talk about the each medication separately, it really makes it easy.Bethanecol. It is used for treatment of post operative and post partum urinary retention. So, after surgery when they get anesthesia, they don’t have much sensation and their urinary, they often get the urinary retention. So, this medication helps relieve urinary retention because it causes urinary contraction. And also to treat the neurogenic bladder atony.Carbachol and Pilocarpine. This one, it causes the myosis, that means pupil constriction. So, when it causes the pupil constriction, it’s easier to do the examination. That’s why, it’s also used very often in the ophthalmic procedures as well. This one also decrease the intraocular pressure in the glaucoma. So this is, this medication are used in for glaucoma. And also, to perform certain procedures by the surgeon like eye procedures, ophthalmic procedures.So, those were the 3 main medications. So, what about their side effects and contraindication. So, whenever you give this medication, it only, it helps in, let’s say, for urinary retention, for ophthalmic agents. However, they have other effects like parasympathetic nervous system is present in many other organs. So, these medications gonna have some effect on those organs as well. And those effects, basically, it’s side effects. Like, it causes the nausea, vomiting, diarrhea. Now, it’s gonna increase the GI motility, if you remember. Like, if you activate the parasympathetic nervous system, it increase the GI motility as well, so, it can cause the abdominal cramp. It increases salivation, if you remember the effect of parasympathetic nervous system on salivary glands. Involuntary defecation, because all the sphincters in GI are relaxed. So, it can cause involuntary defecation. It decreases the heart rate, so, it can cause the bradycardia, as well as the heart block, decreases the blood pressure, cardiac arrest. So, this is basically all the effect of parasympathetic nervous system which we do not want. Let’s say, if you’re giving a Pilocarpine medication, as we talked in the previous slide, to induce the myosis for pupil contraction, however, this Pilocarpine is parasympathomimetic drug. It’s gonna have effect on all other organs where the parasympathetic nervous system is present, like GI, heart. So, wherever the effect, it causes on the other organs, its side effects, basically. Urinary urgency, flushing and increase in sweating.So, contraindication. So, this medication, if they have had a recent bladder surgery, you do not want to give this medication because it actually increase the contraction of urinary bladder and can cause more problems if they had a recent bladder surgery. Or, bladder obstruction. If they have a GI obstruction like any kind of intestinal obstruction because it increase the GI motility. If they have obstruction, there is a high chance they can rupture the intestine because it increases the pressure or like motility. If they have a history of hypotension or bradycardia, you don’t want to give this medication as well because it can cause, it can slow down the heart. And if they have a peptic ulcer because parasympathetic nervous system increase the GI system, increasing the secretions of all the enzymes and everything as well. So, if they have a peptic ulcer, you do not wanna give this medication. Because if you give this medication, it actually gonna increase the acid secretion in the stomach and gonna cause more problem if they already have peptic ulcer. So, that was the direct acting parasympathomimetic drugs.Now, Indirect Acting Parasympathomimetic System. In order to understand these drugs, let me draw 2 neurons. So, this is axons, (I’m not a pretty drawer) this is their body, this is their dendrites. Okay, so this is a neuron. There’s another neuron, and if you remember the anatomy and physiology of neuron, they are not attached to each other. And, two neurons. The way they talk to each other, is, this is the first neuron and this is the second, let’s say. Now, if first neuron wants to talk to second one, since, it’s not directly attached, it will release a neurotransmitter, right here in this gap right here. And this neurotransmitter will go and bind to this here, and transfer a message, whatever the first neuron wants to tell to the second neuron. Now, that’s the neurotransmitter for the parasympathetic nervous system is acetylcholine which is also known as ‘Ach.’ Now, when the first neuron releases the acetylcholine and second neuron responds to it, once the second neuron responds to it, the acetylcholine work is done. Now, they do not need acetylcholine right here. So, what will happen, this enzyme called cholinesterase enzyme will come and break down some of the Ach. Some Ach will be taken back by this first neuron. So, the old acetylcholine will be cleared once the message is transferred. Now, what if we block this enzyme? If we block this enzyme, acetylcholine will be present in this gap for longer period of time. And it will be able to deliver message repetitively, right here, on to the second neurons. So, it will increase the effect of parasympathetic nervous system because acetylcholine is transferring the message for parasympathetic nervous system. Because, it is parasympathetic nervous system’s neurotransmitter. So, since these medications do not act directly on acetylcholine, that’s why they are called indirectly acting parasympathomimetic because it increases the effect of acetylcholine and it increases the effect of parasympathetic nervous system. But, not by directly working on acetylcholine, instead, it blocks the cholinesterase. So, that’s why it’s called indirect acting parasympathomimetic drugs. So, that’s the mechanism of action.Let’s talk about what are the medications are in this class and what are the indications are. So, let’s talk about the first 3 right here. Neostigmine, Pyridostigmine, Ambenonium. So, these medications are used for the treatment of myasthenia gravis. So, if you remember, on myasthenia gravis is basically breakdown of acetylcholine receptors. So, decrease in acetylcholine activity. So, these drugs can be used to increase the acetylcholine effect in myasthenia gravis.There’s another drug, it’s Edrophonium. This is for the diagnosis of myasthenia gravis and also to differentiate between the myasthenia gravis and cholinergic crisis. So, now, as we know, like a myasthenia gravis, whenever they have a decreased level of acetylcholine, it will cause myasthenia gravis. Now, in cholinergic crisis, it will be increased level of Ach, right? Now, this drug is particularly used for diagnosis, like to differentiate bacause the signs and symptoms of myasthenia gravis and cholinergic crisis are same. So, from the signs and symptoms, you cannot differentiate if this patient is having a cholinergic crisis or myasthenia gravis. Because, if a patient is on this 3, these drugs, let’s say, Neostigmine, patient is on the Neostigmine for the myasthenia gravis. If a patient comes with symptoms of weakness, fatigue and like that, that’s the symptoms of myasthenia gravis. Well, it is the symptoms of cholinergic crisis as well. So, how do you find out that if patient took this medication too much, and did have a cholinergic crisis or this patient does not have enough medication, like patient needs a little bit more dose in order to cure the myasthenia gravis? So, you give this drug, it’s called edrophonium. And the reason we use this drug, it has a certain duration of action so you can just really diagnose fast and it wears off from the body. So, when you give this drug and if their symptoms get relieved, let’s say, if they have fatigue, weakness, like that, and if you give these drugs and their weakness is gone, their fatigue is gone, that means they have myasthenia gravis. They need a little bit more drug in order to cure the myasthenia gravis because these drugs patient is on are not enough. They need more dose. But, what happens, like if you give these drugs and their weakness becomes, like they become more weak, they become more fatigued, that means they are having a cholinergic crisis. Because, they have already too much drug in their body and if you give the Edrophonium, the same drug, it causes, it worsens the symptoms. That means, increased level of the same drug. So, it is cholinergic crisis. So, basically, that’s the reason they use this Edrophonium drug. And this is really important question in NCLEX as well, like which drug is used to differentiate between the myasthenia gravis and cholinergic crisis. Or, which drug is used to diagnose myasthenia gravis?The other drugs in this categories, Tacrine, Galantamine, Rivastigmine, Donepezil, Physostigmine. They are all for the Alzheimer’s disease. Because there’s no actually set cause of Alzheimer’s Disease. To think, it is decreased level of acetylcholine in the brain. And this drug has shown the decrease ‘cause you cannot stop the progression of the Alzheimer, you can only slow. So, after giving this medication, it has shown that the progression of Alzheimer’s disease has goes slow. So, that’s why they use these drugs in Alzheimer, not to cure, but to slow the process of Alzheimer.What are the side effects of Parasympathomimetic? They are the same exact side effects like direct acting parasympathomimetic like nausea, vomiting. Because, you remember, like acetylcholine, also present in other organs. You want this medication for only particular organ. For example, in past this one, you wanted to treat myasthenia gravis and Alzheimer’s disease. But, this medication gonna go to the liver, gonna go to the heart, gonna go to the intestine, gonna go to the bladder and gonna cause these effects. So, those are the side effects. Like, nausea, vomiting, diarrhea, abdominal cramps, increase in salivation, involuntary defecation, the heart side effects, bradycardia, heart block, hypotension, it can cause the cardiac arrest, urinary side effects, urgency, it can cause the headaches, flushing and drowsiness as well. The same contraindication. You don’t wanna use it with the bradycardia, urinary tract obstruction, Parkinson. Here, you don’t wanna use it in Parkinson, the reason is, Parkinson’s disease, there is already an increased level of acetylcholine. You do not want to give these drugs and even increase more acetylcholine. So, you can’t give these drugs in Parkinson if you know about the disease process. In patho, you just figure out, like you can’t really give this medication in Parkinson because there’s already increased acetylcholine level. Athma. Peptic ulcer. Cardiac Arrhythmia. And Epilepsy. And you don’t wanna give this in asthma because if you remember, the parasympathetic nervous system effect on respiratory system is to decrease, constrict the bronchial muscles. So, if you give this medication to a patient who has asthma, it’s gonna make the asthma worst. Okay.And this is a, I haven’t seen many questions asking this antidote, but since we’re talking about this direct acting parasympathomimetic drug, Pralidoxine is the antidote for indirect-acting parasympathomimetic drugs. And, you have to give within 30 minutes. So, the medication we talked about, they are all reversible. But there’s some irreversible indirect acting medication. I mean, not medication, indirectly acting agents. Indirect acting parasympathomimetic agents are available. And they will just bind to it and they will not, they’re irreversible, you cannot reverse unless you give this antidote in 30 minutes. And these drugs was used, if I’m not wrong, these were drugs, these agents irreversible indirectly acting parasympathomimetic agents were used in either World War I or World War II as a chemical weapons against the armies because they are basically paralyze them. So, that’s why you wanna be really careful and this is the antidote. Okay.This is it about this parasympathomimetic as a direct and indirect acting classes. I know this is a little bit complicated classes as far as ANS drugs. But if you have any questions, you can ask or email us anytime. Thanks for watching.
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