14.01 Autonomic Nervous System (ANS)

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Autonomic nervous system. We gonna go over the autonomic nervous system a little bit in detail about the autonomic nervous system before we go and understand the drugs. This will help us to understand drugs’ mechanism of action and side effects. It will be really easy to remember as well.

So, let’s take a look at the first slide. Now, you have seen this table and all these explanation probably many times in your nursing school. Like a, Sympathetic Nervous System is Fight or Flight response and Parasympathetic Nervous System is Rest and Digest Nervous System. And in Sympathetic nervous system, heart rate is gonna go up, bronchial smooth muscles gonna relax, arteries gonna contract, salivary gland gonna be inhibit salivation. So, all these things, you see here, all the things here and for the Parasympathetic as well. Let’s talk a little bit in detail for each one. So, when the sympathetic nervous system activates, and because of the fight or flight response, then you need a little bit more blood in all your skeletal muscle and all in the body because they need to produce the energy to contract the threat that your body is anticipating. That’s why the heart rate’s gonna go up. Now, the bronchial muscle is gonna relax because your lung needs more air, I mean, oxygen, that’s why the bronchial muscle is gonna relax and the air is gonna be a little bit more dilated so your lungs can get more air. Arteries gonna contract, so, your blood pressure is gonna go up, and that’s how your skeletal muscles most probably that you gonna use in the fight and flight response can get more blood. Now, salivary gland, GI tract muscle wall, GI tract Sphincters, you don’t really need GI system really active at this moment when you are, your body or your senses are threatened and you need to act quickly. So, this salivary can inhibit salivation. GI tract muscles gonna relax, so, there won’t be any peristalsis movements. GI Sphincters gonna contract. So, that’s why these 3 things gonna be inhibit the GI thing. Urinary bladder is gonna relax, so your urinary bladder can hold more urine. As well as the liver, you will need a lot more energy than you require in normal status. So, gluconeogenesis and glycogenolysis gonna happen in liver and the blood glucose level is gonna go up in order to produce more energy. Kidney, renin secretion is gonna happen, so, renin is gonna start the RAA system and your blood pressure will go up. And the fluid volume will go up as well, in your body as well. And definitely, you know, sex organs are gonna be inhibited as well.

And, it’s totally opposite in the parasympathetic nervous system. So, like a heart rate is gonna increase in sympathetic nervous system, it’s gonna decrease in parasympathetic. Bronchial muscle is gonna relax in sympathetic, it’s gonna contract in parasympathetic nervous system. Now, we have looked at this description a lot of time. Let’s take a look at into a little bit detail and see if we can break this thing down and understand a little bit in more detail.

Alright. So, autonomic nervous system. Here’s our brain, I’m not really a good painter, and here’s our spinal cord. So, there are two branches for autonomic nervous system. If you can, ANS. Preganglionic and Postganglionic. Now, you need to remember this, I mean, not really remember, but understand, in order to understand all the branches of parasympathetic and sympathetic nervous system as well as the drugs as well. So, we have some neurons in central nervous system which is here and all the way up to down. And the other neurons comes out of the spinal cord, right here, like that. Those are called peripheral nervous system. Peripheral nervous system, because they are not central, they are peripheral. Now, the neuron originates from the central nervous system. This is a neuron, this is axon, this is the body, (this is body, this is axon) of neuron, if you know the anatomy of the neuron. This is dendrites. So, say, this is sympathetic nervous system, and this is parasympathetic nervous system. Here we go, this is the same neuron, dendrites, okay. Now, this part, in both SNS, sympathetic nervous system and parasympathetic nervous system, we gonna say preganglionic neurons. These neurons are located in the central nervous system, not in the peripheral. Okay. Now, there’s another neuron axons that’s gonna be right here, this is dendrites and here’s the target tissue. (Target Tissue) And, here as well, this is dendrites and this is a target tissue. So, this part, it’s gonna be in the whole part, it’s gonna be in central nervous system and this part is peripheral nervous system. Okay. Now, these neurons, like when the neurons, these neurons get any kind of command from the brain, this neuron is gonna talk to this, the first neuron is gonna talk to this neuron as like the front one, this one is gonna talk to this one. So, this is preganglionic, this is postganglionic neurons. Now, the main point I wanted to tell you about this thing is this preganglionic neuron which is located either in the brain or spinal cord are cholinergic. These are cholinergic, okay? That means, when this neurons gets excited, this is gonna secrete here a neurotransmitter ‘Ach’ that is Acetylcholine. Same here. Doesn’t matter if it is sympathetic nervous system or parasympathetic nervous system. Now, if this neuron gets excited, and secretes the acetylcholine and it talked to this second neuron, then, if this is a sympathetic nervous system, this is gonna release the sympathetic nervous system neurotransmitter. If it is parasympathetic nervous system, neurons is gonna secrete parasympathetic nervous system neurotransmitter which we gonna talk about which neurotransmitters are for which nervous system in the following slides. So, this is kinda, I wanted to make a point. This like, all the preganglionic neurons are cholinergic. And, all the post ganglionic neurons, are depends. If it is sympathetic nervous system branch, it’s gonna be adrenergic. If it is a parasympathetic, then it is cholinergic. So, like, if you take a look at, like a parasympathetic nervous system the preganglionic and postganglionic neurons are both gonna be cholinergic while the sympathetic nervous system, the preganglionic neurons are gonna be cholinergic and the postganglionic is gonna be adrenergic.

Alright, So, let’s take a look into each sympathetic nervous system. The sympathetic nervous system and parasympathetic nervous system in detail. So, as we told, this is just a, this diagram is basically explaining that we talked in the previous slide. Preganglionic. So, this is kinda like the central nervous system, the preganglionic neurons are right there and the postganglionic neurons are right here. So, sympathetic nervous system. The main neurotransmitter for the sympathetic nervous system are epinephrine, and norepinephrine, they are also called as cathecolamine. Now, there are many names for sympathetic nervous system. Some would say ‘adrenergic’ as well. It’s the same thing. So, you can say adrenergic or sympathetic nervous system. They are both the same thing. And the neurotransmitters, our main neurotransmitters for them, so like when I say, neurotransmitter, it means like one neuron talks to the another neuron. Like as we talked in like this is a neuron, now, the neurons are not connected to each other, okay? If you remember Anatomy and Physiology. So, if this neuron has to talk to this neuron, how does it talk? This neuron is gonna release the neurotransmitter, right here, from its dendrites right here. And this neurotransmitters gonna go and attach to the axon of the another neuron. And depending on which neurotransmitter is being secreted from the first neuron, the second neuron is gonna receive the message accordingly.

Okay, now, Sympathetic Nervous System. There are 4 different receptors for sympathetic nervous system. This is really important to remember because this will help in the medication and to remember which pharmacological class medications work, which way and for which disease. So, there are 4 receptors. Here, the alpha receptors and beta receptors. They are further divided in alpha 1, alpha 2, beta 1 and beta 2. Now, where they are located. Alpha 1 are located into the all sympathetic organs excluding the heart. So, this alpha 1 receptors, you’ll see mostly, you won’t see in heart, but you’ll see in the vessels, in the liver, etc, like all other organs. Alpha 2 receptor. Now, this is kinda tricky. Alpha 2. Alpha 2 receptors are located in central nervous system only. Like they are not present in peripheral nervous system. So, their neurons extend to the central nervous system, to like to, up to the brain only and spinal cord. Spinal cord, SC. The beta 1 receptors are located on heart and kidneys. Beta 2 receptors are located on all sympathetic organs excluding heart and they are located mainly in the bronchial and uterine vascular smooth muscles. Sorry, I forgot to write down that one right there. So, if you remember these 4 things, it will be much easier to understand the sympathetic nervous system and drugs as well.

Alright. Next slide. So, we know, these receptors are located on which organ. Let’s talk about a little bit what do we, what will happen if we excite these receptors. So, if we excite, if we give a drug that goes and binds to specifically alpha 1 receptors, what will happen? It will cause the vasoconstriction. So, it will do all the things that we look into that first table in sympathetic nervous system except increase in the heart rate, basically, because it’s not present in heart. So, vasoconstriction, increase in blood glucose level, and etc, like all the other sympathetic nervous system symptoms. Now, when you excite this alpha 2 receptor, remember, I told you in the previous slide, this is a little bit tricky. Now, when any drugs, when we give any drugs that goes to the brain and spinal cord, means the central nervous system and binds to these alpha 2 receptors, it decreases the epinephrine and norepinephrine level. So, basically, what I’m saying is, when you give a drug that goes and binds to alpha 2 and potention, it actually decreases the sympathetic nervous system effect. So, it’s kinda opposite. Like, when you excite alpha 2. It’s gonna decrease the sympathetic nervous system. Now, beta 2. I’m sorry, beta 1. They are present in heart and kidneys. So, when you excite this, when you give a medication, it’ gonna go and bind to beta 1. What it’s gonna go and work on heart and kidney. So, it’s gonna increase the heart rate, force of contraction of heart and increase kidney blood flow. ‘Cause what this does, it’s like when beta 2 gets excited by any drugs on kidneys, it actually dilates kidney blood vessels. Okay. Now, the last receptor is beta 2. Now, this receptor is present in all organs except the, except heart, and mainly in bronchial and uterine vascular smooth muscle. So, it’s gonna actually, when you give a drug, that’s gonna go and bind to the beta 2 specific receptor, it’s gonna dilate the bronchial and uterine smooth muscle. Now, at the same time, it’s present in other organs as well, like the liver, GI, and everything. So, it’s definitely gonna decrease the GI motility, it’s gonna increase the blood glucose level, and etc., all fact you see when you excite the sympathetic nervous system on the body. Now, when you excite this beta 2, it’s not gonna increase the heart rate since those receptors are not present in the heart. So, this is a basic explanation about the all receptor that are present in our body, like sympathetic nervous system receptors and all the drugs that we give for specific receptor, has a specific effect, depending on what receptor they bind to. And the side effect is gonna be the things that we don’t want. Let’s say, for example, in beta 1. If we give a drug that excites, they gonna go and bind with beta 1 receptor. Now, it’s gonna actually heart and kidney but at the same time, it may go to different organs and bind as well and it’s gonna cause the sympathetic activity. Like, decrease in GI motility, increase in blood glucose level and decrease in salivation, salivary glands production, so forth. Those are pretty much gonna be the side effects. Okay. And we’ll go and discuss each class in detail in the following videos.

Now, Parasympathetic Nervous System. The main neurotransmitter present in parasympathetic nervous system is acetylcholine. And as we talked about like in the first slide, is this is the central nervous system, the brain and the spinal cord, and this is goes to like a post ganglionic neurons. All the neurons are here are preganglionic, these are all postganglionic neurons. So, that’s the parasympathetic nervous system.

Now, let’s take a look at the receptors. Now, there are only 2 types of receptors. Muscaranic and Nicotinic receptors. Now, here, nicotinic receptors. You will find this nicotinic recceptors except the smooth muscles, in the smooth muscles in the postganglionic neurons. That’s it. They’re not in the heart, kidneys or anywhere. While the most of the parasympathetic nervous system receptors are muscaranic receptors. Like heart and all the targeted parasympathetic organs. So, this is kinda easy to remember compared to the sympathetic, it has 4 receptors like alpha 1, alpha 2, beta 1 and beta 2.

So, that was about the nervous system, parasympathetic nervous system and the sympathetic nervous system. I hope you find this helpful. We’ll go and discuss each class in detail in the sympathomimetic, I mean, sympathetic nervous system drugs and parasympathetic nervous system drugs. Thanks for watching.

Sympathomimetic drugs. Also called, known as adrenergic agonist medication. People say adrenergic drugs, there are different words that people use for this ANS drugs. And I highly recommend that you watch the autonomic nervous system video before you watch this one because it will help you to understand all the different receptors in the sympathetic nervous system and parasympathetic nervous system has and what are the physiological responses when you activate or if there is a medication that goes and binds to the receptor and activate them. In this video, we gonna learn about the sympathomimetic drugs based in, I have divided these drugs in a 3 section to Mixed agonist. And in this medication, in this section, we’ll look at the medication that works on more than 1 sympathetic nervous system receptors. Alpha agonist, we’ll, in that one, take a look the medication that particularly works for on the alpha 1 and then alpha 2. And we’ll take a look at into this lastly the Beta agonist, especially, we’ll go over Beta 2 agonist medication that goes and binds to this beta 2 receptors in our body.

So, let’s take a look in the Mixed Agonist. The first drugs we gonna take a look at into is the Epinephrine. And this is really important drug, not only as a nurse that you need to know in, for NCLEX, but this is really important drug if you gonna work in an intensive care unit after you become a nurse. ‘Cause you’ll be using this drugs a lot of time as a drips and also some mostly in code blues as well. Mostly, not mostly, but all the time, I would say. So, these drugs work on 3 different receptors in our body. The Alpha 1, Beta 1 and Beta 2. And these are the sympathetic nervous system receptors. When these drugs goes and binds to alpha 1 receptors in our body, what it does, it causes the vasoconstriction, and it increases the drainage of aqueous humor and decreases the intraocular pressure because that aqueous humor gets drainage out of the eye, that will decrease the intraocular pressure. Now, when this drug goes and binds to the beta 1, it has a positive inotropic and chronotropic. So, it will increase the force of contraction rate, I mean, heart rate. Force of contraction of heart, heart rate and eventually it will, this will increase the cardiac output. And finally, this medication also works as a, on the beta 2 receptors in our body which will relax the bronchial smooth muscles and vascular smooth muscles. So, what it will do, it will cause the bronchial smooth muscle relaxation, so the trachea will enlarge and there will be, air movement will be easy throughout the lung. And when it relaxes the vascular smooth muscles, it’s gonna cause the vasodilation. Now, there’s a thing to remember. The beta 2 receptor are, like if you have watched the autonomic nervous system video, the beta 2 receptors are mainly located into the bronchial smooth muscles. There are only few from our present in vascular smooth muscles. So, even though it causes the vasodilation, vasodilation is not a significant. So, the blood pressure does not decrease significantly. And this beta 2 vasodilation will be over shadowed by alpha 1 because when the alpha 1 mostly present in the vascular smooth muscle, it will cause the vasoconstriction, so the blood pressure will go up ‘cause this effect is gonna be more compared to this beta 2 vasodilation. Because there are not too many receptors, there are not too many beta 2 receptor present on the vessels. So, if you, now we understood the mechanism of action and what receptor it binds to and what is the physiological response of this epinephrine drug.

Let’s take a look into the indication like in which disease process we can use this drug and what are the side effects. So, obviously, definitely, in shock, we can use this medication. And the reason we use this in shock is usually like either if it is a hypovolemic shock, if it is a septic shock, or cardiogenic shock, or neurogenic shock, mostly happens is the decrease in blood pressure. And, we will use this drug as a IV drip to increases the blood pressure and also to increase the force, and the force of the contraction of the heart and also the rate. So, the cardiac output will increase as well. So, all the vitals organ in our body get perfused. Since this medication also relaxes the bronchial smooth muscles, we can use this medication for the bronchospasm. Now, what if we give this medication for the bronchospasm IV? Well, it’s gonna definitely have a effect on different organs on top of this bronchial smooth muscles. So, that is the reason, whenever there’s a bronchospasm, we give the racemic mixture of epinephrine. Now, when we give the racemic mixture, what I mean by that, is this epinephrine will be diluted into the normal saline and the concentration of the epinephrine will be so low and will give this one as a breathing treatment. So, we’ll give as a aerosols or inhalers, kinda like that stuff. So, have a local effect in the bronchial muscles only, not throughout the body. So, that’s kinda interesting thing too. And also, we use this medication for glaucoma, as well as it decreases the intraocular pressure. Since this one causes the vasoconstriction, so, what if we give if this medication locally to a certain area of the body? Let’s say, if we need to give a local anesthetic medication. They usually give this epinephrine with the local anesthetic. And the reason they do, it’s this one will cause the local vasoconstriction . Now, it will cause the vasoconstriction, so the medication, the anesthetic medication, the local anesthetic that we give will stay in the area for a longer time compared to, compared when we give it on without this epinephrine. So, they usually use this medication with anesthetic. So, the anesthetic medication effect will stay longer than usual. And also, this medication also we use this one for hypotension since it causes the potent vasoconstriction.

Let’s take a look at into the side effects as well. Now, whenever we think about the side effects of any kind of anes drugs, is usually the physiological effect this medication has on our body that we do not want. So, for example, for this epinephrine, well, they do not want any kind of GI effect. Let’s say their blood pressure is going down and we want to give this medication to increase the blood pressure. However, if you look at into the sympathetic nervous system, there are many other effects sympathetic nervous system has on our different body parts like the GI. Now, we don’t want GI effect. So, but, it will have GI effect. So, it can cause nausea, vomiting and kinda like that stuff as a side effects. Like a, sometime it can increase the heart rate really high. So, the patient may feel the heart palpitation, it can cause the cardiac arrhythmia as well, sweating and also the headache. Now, since, this also this medication is used for hypotension, but if we give it too much, it can cause a hypertension. And when you, like, when you will start working in the intensive care unit after you’re done with the nursing, you may see they are many patient, like one patient will react differently than other patients especially for this IV vasopressors, so like this epinephrine, norepinephrine, dopamine, dobutamine, all kind of medication that we use in critical care. All the patient will react differently. So, you have to be really careful when you’re titrating this drug in order to achieve the goal blood pressure.

Okay. The next medication, we gonna take a look into the norepinephrine. Now, if you remember, the epinephrine has a effect in alpha 1, beta 1 and beta 2. However, this drug does not have effect on beta 2. These drugs work on alpha 1 and beta 1. When it works on the alpha 1, it causes the vasoconstriction, and decreases the intraocular pressure. In beta 1, positive inotropic and chronotropic gonna increase the force of contraction and the rate of contraction in the heart. And eventually, it gonna increases the cardiac output. So, what are the indication? We can use this for the shock. We talked in the previous slide as well that in the shock, it causes the like hypotension, like a vasodilation throughout the body. In most of the shock, then we can use this medication for the, to increase the blood pressure. So, all the vitals organs can get perfused. Hypotension and Cardiac Arrest. So, now, and also, the side effects is gonna be the same as we talked in the previous slide. It’s like all these arrhythmia, hypertension, heart palpitation, headache, nausea, vomiting and sweating.

Now, the next drug is dopamine. This is really interesting drug and important drug to know, falls into the mixed agonist category. Now, this medication is dose dependent. So, dopamine, when you give this medication 2 to 5 mcg/kg/min, it works only on dopamine receptors. And what does this dopamine receptor does? It dilates the renal and coronary and splachnic vessels. And when it does, the kidney will get more blood flow. Since the vasodilation will decrease (the blood flow), the pressure in the kidneys. So, that’s why we use this medication sometime in the cardiogenic shock. So, the kidney can get the enough blood perfusion. Now, in the beta 1, when we give this medication from 5 to 10 mcg/kg/min concentration, it will work on beta 1. And when it works on the beta 1, we’ll have positive inotropic and chronotropic effect which will increase the heart rate and the cardiac output. I mean, the force of contraction as well. And that will increase the cardiac output. However, if we give dose greater than 10 mcg/kg/min, it’s gonna cause the potent vasoconstriction, it gonna increases the blood pressure. So, this drug is kinda is totally dependent on how much dose you give to a patient. Now, it will have that kind of physiological effect accordingly. So, that’s why there are like a different uses for this medication. We can use this medication to increase the blood pressure, if we give dose higher than 10 mcg/kg/min. We can increase the blood flow to the kidney if we give dose between 2 to 5 mcg/kg/min, and can use this medication for the cardiogenic shock if you use this medication in this concentration because it will increase the cardiac output and the, also will increase the heart rate and also the force of contraction. So, these drugs are kinda little bit interesting also and tricky at the same time.

The next drug is dobutamine. Now, dobutamine works on beta 1 and beta 2. This medication does not have any effect on dopamine receptors because this medication is kinda like people always get confused with dopamine ‘cause they kinda like look like the same, they kinda like sounds like the same, but there’s a difference. Dobutamine does not work on dopamine receptors. However, this is kinda good drug than dopamine. If we have to just, if you’re just giving it for the congestive heart failure or cardiogenic shock, because this one particularly works on beta 1. And that will have a positive inotopic and chronotropic effect, then increase the heart rate and cardiac output as well. Now, when it works on the beta 2, I told you, like there are not many beta 2 receptors on vessels, blood vessels, however, there are some. So, it can cause the vasodilation. Now, when it increases the heart rate, and force of contraction plus decreases the systemic vascular resistance, which is blood pressure, by doing this vasodilation, heart workload will be decreased. ‘Cause heart won’t have to pump really hard in order to get the blood out of the heart because there’s not much systemic vascular resistance. So, this medication is really really good for congestive heart failure and also for the cardiogenic shock and usually, this medication is also used as IV medication, IV drips in critical care areas. And this is not a dose dependent drugs as well. This is not a dose dependent drugs like dopamine.

Now, the next category we gonna take a look at into the Alpha 1 agonist. Now, there’s a main 4 drugs fall into this category. Phenylephrine, Methoxamine, Metaraminol and Midodrine. And when this medication goes and binds to alpha 1 receptors in our vessels, it causes the potent vasoconstriction. That’s why we can use this medication in a shock where we have to increase the blood pressure, to maintain the blood pressure during anesthesia, because if a patient is under anesthesia effect, they get the hypotension, so we can use this one. And also, for the orthostatic hypotension. I have seen Midodrine used for orthostatic hypotension often. Now, if we use this medication as a nasal spray, it can decreases the nasal congestion. Because there are small blood vessels in our nose, in nasal area, what happens during the nasal congestion, because there’s so much secretion, either due to the allergy, or any kind of, some kind of reason. That they secretes the more, more secretions in our nose and that causes the nasal congestion. They are dilated during the nasal congestion. So, when we give this medication as the nasal spray, it will cause the potent vasoconstriction in our nasal area. And what it will do, it will decrease the all secretion in our nose. So, that’s why we can use this medication for nasal congestion as well. So, if you’re using this medication as a nasal spray, it may not have a systemic effect but in some cases, if people use it more than the recommended, it can have really bad systemic effect. Like it can cause the high blood pressure, heart rate’s gonna go up, and so forth. Now, the side effects, is like, as we talked like the side effects of this medication are the non-wanted physiological effect of the medication that we gonna have. So, like you know, like a sympathetic nervous system, it get activated, you can have anxiety, restless, like all kind of stuff. You can have EKG change, blurred vision, fatigue, can go to depression, it can cause the cardiac arrhythmia, and since it decrease in urine output, and GI system is gonna be inhibited, so, it can cause the anorexia as well.

Okay. Alpha 2 agonist. This is also really good interesting category to learn. Now, since if you have watched the autonomic nervous system video, whenever we excite this alpha 2 receptor, which are located centrally. Remember, these receptors are located centrally. When we excite these receptors, if we give a medication that goes and binds to this receptors, it’s gonna decrease sympathetic nervous system, okay? So, it’s gonna do the actually opposite by exciting this receptor, exciting this sympathetic nervous receptor which are located centrally in brain, it’s gonna decreases the sympathetic nervous system effect peripherally. So, this medication can cause the, will cause the vasodilation since it gonna decreases the sympathetic nervous system effect peripherally. Now, the medication that falls into this category is Clonidine, Methyldopa, and this is really an interesting drug too, Dexmedetomidine. And I’ll get back to that one really quick once we are done with this. So, it causes the vasodilation. So, this medication can be used for high blood pressure, and this medication, one of them is used for the sedation and that is Dexmedetomidine. It took me a long time to pronounce that. Alright. It’s also called the Precedex, that’s the trade name. Precedex. And usually used as a IV drips in a critical area for the sedation. Because this medication goes and binds to the alpha 2 receptor located in the brain and causes the sedation. And, if a patient on this medication, you have to be really really careful because I have seen many patient, when we put this medication on for sedation, their blood pressure drops significantly. Like if they’re running like, let’s say, 160/80. They will drop to like 90/60 like in 15/20 minutes if they are so labile to this medication. So, sometime, if you put the patient on this medication, you may need another vasopressor like a phenylephrine which is alpha 1 agonist and as we talked previously, like epinephrine or norepinephrine vasopressor in order to make sure we maintain the blood enough blood pressure. So, that’s the medication, this kinda really interesting to know that we use it in critical care more often for sedation. So, the side effects, this medication can cause drowsiness, dizziness, dry mouth. And if we stop this medication, like if a patient on this medication, to decrease their blood pressure, for some reason, if they stop this medication suddenly, they can have a rebound hypertension and the blood pressure can go really really up. So, this is one of the side effects. Precaution. You don’t really wanna give this medication for a patient who has a recent MI, cerebral vascular accident or stroke, Diabetes Mellitus, because, you know, like sympathetic nervous system works on liver, it can increase the glucose production. It can cause the increase in blood glucose level, okay? So, you really wanna be either careful, or avoid this medication if a patient has a Diabetes Mellitus. And renal and liver disease, if a patient has, you wanna avoid this medication as well.

Alright. The next one and the last one, Beta 2 Agonist. The medication that falls under this category are Albuterol, Formoterol, Isoproterenol, Metoproterenol, Ritodine, Salmeterol and Terbutaline. What is does, as we remember, from autonomic nervous system video, that these receptors are present in bronchial smooth muscles, and uterine smooth muscles. So, when we give this medication, and activates this beta 2 receptors present here, bronchial and uterine smooth muscle is gonna dilate, both of these smooth muscles. So, and it will have the physiological effect. If they do these things, we can use this medication for asthma, we can use this to treat shock and ventricular arrhythmia, and this is for only Isoproterenol, because it has beta 1 effect as well. The other medication in this category has only beta 2, so, like this one is beta 2, only beta 2, this is beta 2 as well, this beta 2, beta 2, these are all beta 2 except this Isoproterenol. Now, there’s a Ritodrine (Sorry, I missed out that one. It’s not Ritodrine), it’s Ritodine. That medication also used to slow the uterine contraction in a pregnant woman. So, that’s the only medication has been used for right now, currently. And these medications are kinda interesting to know. If you know Albuterol, it’s used for like asthma because these are like really short acting. Like, it works in minutes. So, you wanna give this medication for like status (Sorry, not status), in asthma, when there are respiratory system is compromised and they can’t really breathe. This medication works really fast compared to the other medication in these categories. The side effects as usual, there are all other physiological effect that we do not want is restless, anxiety and tremor, headache, tachycardia, it can cause really bad heart pain; angina. And there’s also another thing to like this medication only works on beta 2, but it can have another physiological effect. So, usually, this medication, if you’re giving for asthma, we can give it as a inhaler or nebulizer, like that, but still, it’s gonna have some absorbance systematically. Systemic Absorption. So, that’s why it can cause these side effects. It can cause MI, heart palpitations, and GI system unwanted effect like nausea, vomiting, anorexia. It can cause really bad pupil dilation and muscle cramps.

Okay, so, that was it about in sympathomimetic drugs. I hope you understand really well. If you have any questions, let us know or e-mail us. Thanks for watching.

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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