I'm Professor Jim Hoffman and I want to welcome you to Pharmacology for Nursing. In this video we're going to be looking at the content for topic three, Physiology Concepts, and as you look at your learning objectives in Canvas, just keep in mind that under the Nursing Pharmacology text, that is the online text, and those Reference points, the 4.2, 6.2, and 10.2, those are hyperlinks to take you directly to that section of the textbook, so please take advantage of that. Our objectives, we're going to spend, the first three objectives are covering information on the autonomic nervous system. Next we're looking at the renin-angiotensin-aldosterone system. along with that relationship back to the sympathetic nervous system or autonomic nervous system. And then finally, a few comments about the inflammatory process from a physiological perspective. Before we get into the autonomic nervous system, the overall purpose of this content and this topic is to remind you of the importance of understanding your basic anatomy and physiology and pathophysiology from your science classes. Those are going to be extremely important in helping you understand the medications we're using, the pharmacodynamics in particular of the medications, because again, the pharmacodynamics are looking at the effects that the drug causes on the body. And if we go back to basic definitions, a drug is any chemical that produces an effect or changes a response within the body. So again, we're looking at FDA approved drugs in this course primarily. And we're looking at how do we produce the responses. Now the kind of responses we're going to be looking for from the drugs is going to be usually going to be one of four responses. The first two go together. First is we're going to use drugs that will either mimic or stimulate normal functions, normal physiology of the body. So we're going to try to create or stimulate normally occurring processes. The second use of drugs is to inhibit or block those normal activities. So those two concepts are going to be. Now, particularly useful to keep in mind for the first several classes we look at, because all those classes are looking at drugs that will either, again, be an agonist, which means it will stimulate or mimic a normal physiological function, or it's going to be an antagonist, which means the purpose of the drug is to block a normal function, to slow things, to inhibit certain activities. So those first two pieces go together. And as we get into the first several drug classes we're going to be looking at, that's really the concept that we're dealing with. We're going to be looking at using a drug as an agonist, which means it's going to act the same as naturally occurring chemicals, or it's going to stimulate or mimic the activities at the cell level of normally occurring chemicals in the body and producing those normal responses. Or we're going to be looking at antagonists or blockers, in order to block those processes by either blocking the chemical involved or blocking the receptor sites on the cells where that chemical would normally act. At the beginning of the reading material for the autonomic nervous system, there are several links to an online anatomy and physiology text. If you need to go back and refresh your memory on those basic concepts, please take advantage of that or go back to your A&P book. and pathophysiology text from your classes. So the first part we want to look at is autonomic nervous system. The reason we're looking at it separate is it is concepts, and it's a system that's going to be tied into several of our drug classes, several of the body processes or disease processes we're going to be looking at and being involved with drugs. So we just want to be... Comfortable with the basics. So when we look at the nervous system, you'll remember it's divided in the central nervous system, which will be the brain and the spinal cord, and the peripheral nervous system. On the peripheral nervous system side, we have another breakdown of either motor, which is outgoing messages, or sensory, which is incoming messages, from the body back into the central nervous system and up to the brain for processing. As we take the motor side down and look at... The part of the nervous system that's creating effects in the body, we divide that between somatic activities, things with walking, reaching, things that we process and we actually direct the activity intentionally. And then the autonomic nervous system. That's the one we want to focus on. So the autonomic nervous system is that part of the nervous system that's responsible for all the things our body needs to do without us having to think about it. So they're all the things that happen automatically. We don't have to think about controlling them or doing anything in particular. Our body is just going to respond to cues. signals, triggers, and go through the processes it needs to. So in the autonomic nervous system, we have two sub-components, and this is really where the drugs that we talk about in the next couple modules is going to really focus in on. We have the sympathetic nervous system and we have the parasympathetic nervous system. Sympathetic is the fight or flight, and that's our adrenaline rush side. Parasympathetic is our rest and digest. They basically balance each other in helping the body maintain homeostasis between being in a stress-responsive posture and being in a rest and recovery posture. We constantly go back and forth between those two. A couple other things from this diagram, and again, Now, if you need to go back to your basic A&P to refresh on these, but when we're looking at this use of drugs to either stimulate or block responses within the body, we're working off of the basis of the receptor site or lock and key approach that the tissue, the cells have receptors on them that are specific to certain. Keys are stimuli, and those stimuli or keys are chemicals. So on the sympathetic side, our main chemicals are norepinephrine, epinephrine, dopamine, serotonin also falls in that. As a grouping, those four chemicals are called catecholamines. But primarily we're thinking with sympathetic nervous system, norepinephrine and epinephrine are the two primary ones. On the parasympathetic side, the main chemical we're looking at that serves as a key for the receptor sites is acetylcholine. So from that part, parasympathetic is also going to be called the cholinergic. We're going to borrow that part from acetylcholine. So in discussions and test questions and your readings, you see parasympathetic or cholinergic, they're the same thing. We're going to match up parasympathetic cholinergic as being one in the same as far as terms. On the sympathetic side, again, this is fight or flight. It relies on norepinephrine and epinephrine. Those are both chemicals that are released by the adrenal gland. The other name for epinephrine is adrenaline. So the sympathetic side is also called adrenergic. So if we see references to an adrenergic process or an adrenergic drug, adrenergic agonist or antagonist, we're talking about a drug that affects the sympathetic side. So again, some terms. Sympathetic equals adrenergic. Parasympathetic equals cholinergic. Agonist is a drug that is going to stimulate or mimic the normal activities of the chemicals in the body. Agonist is going to reflect on a drug that inhibits or blocks the normal activities of chemicals. And the chemicals we're talking about again with sympathetic or adrenergic side is primarily norepinephrine and epinephrine. On the parasympathetic side or cholinergic side, we're looking at acetylcholine. At the bottom of the diagram. You'll notice that that receptor site theory, there's a couple differences between the systems. On the sympathetic side, we have four main ones that we're going to be concerned with. They're alpha 1, alpha 2, beta 1, and beta 2. So as we look on the next slide of where the sympathetic or adrenergic site has its impact, it's going to be important to keep in mind and remember that Not each of those organs has all of these receptor sites. So whichever receptor site that organ has, that will need to be triggered by the epinephrine, norepinephrine, or a drug that we're using in order to get that response. Or if we're trying to block it with an antagonist, it has to be a drug that will match up to the appropriate receptor site, whether it's alpha-1, alpha-2, beta-1, beta-2. Uh, so in the next couple of slides, just going to do a real quick refresher of how those. receptor sites are spread out on the parasympathetic side we only have two receptor sites nicotinic and muscarinic and i mentioned that in a couple slides but main thing to keep in mind when we're talking about that rest and digest parasympathetic or cholinergic response that we normally are going to be thinking about we're talking about muscarinic sites and those muscarinic sites are on all those organs so if i If we are using a drug to affect a specific organ using the cholinergic activities, we're also going to see that cholinergic effect on any of the other organs on the parasympathetic side. So there's not very much selectivity at that point. Again, on the sympathetic side, we can have a fairly high degree of selectivity because of the number of receptor sites and the way they're spread through the body. So if we look at the diagram of the parasympathetic and sympathetic site organs as a comparison and their normal effects, we can start getting a picture of this. So if we start on the right side, sympathetic or adrenergic is fight or flight. So things we're going to see happen when those receptor sites on the sympathetic side are stimulated, we're going to see things like pupil dilation. secretions are going to be inhibited. So that includes saliva and secretions in our GI tract. The heart rate is going to accelerate. In our lungs, the bronchi, the large airways, are going to widen out. They're going to dilate. We're going to have some work on the liver to start converting glycogen to glucose to produce more energy. We're also going to have an impact on the adrenal glands to help facilitate or stimulate the secretion of more adrenaline and noradrenaline or epinephrine, nor epinephrine. Again, those words are interchangeable. And we're also going to see an impact on the urinary bladder to inhibit its contraction. So we're going to relax the bladder wall. But we're also going to contract the sphincters at the outlet of the bladder. So at the bladder level, a sympathetic response will be relax the bladder wall so it's not contracting but tighten up on the sphincters to help retain the urine. So that's on the sympathetic side. That's normal function. If we stimulate the sympathetic side, anytime we're in that. Stress, it's not a high stress, it's not a full fight or flight all the time, but anything on that side of the continuum where our body is needing to be really focused. On the parasympathetic side, and again here we're looking at the impacts of acetylcholine on muscarinic sites. On the pupils, we're going to get pupil constriction. It's rest and digest, so we're going to facilitate secretions of the GI tract, so we're going to have an increased flow of saliva. We're going to increase the peristalsis or activity of the intestines. We're going to increase the secretion of fluids throughout the GI tract. At the liver, we're going to stimulate the release of bile because that's involved in the digestive system. In the heart, since we're in the rest phase, we're going to slow the heart rate down. We're not in as great a need for high levels of oxygen, so we're going to allow the bronchi to relax and so they'll constrict somewhat. And then at the bladder, as far as the elimination, on the parasympathetic side, we are going to see an increase in contraction of, or stimulate contraction of the wall of the bladder. of that muscle and a relaxation of the sphincters at the outlet of the bladder. So a cholinergic or parasympathetic response would be to facilitate urination as well as these other things. And again, all of these organs in this site on the parasympathetic are all handled with muscarinic receptors. So acetylcholine or a drug that's used to address an issue involving the GI system with peristalsis and secretions is also going to have an impact on every one of the other organs that are listed the sympathetic side it's not necessarily going to be the case that if we take a drug to affect the heart it may or may not have noticeable effects on a few of the others it's going to depend on which receptor site is present or is involved so in your book It has this table, which just gives a really quick overview of what the effects of stimulation. So these would be the normal responses or the response of a drug that would be considered an agonist on the specific receptor sites. This is going to identify where those receptor sites are and what we expect to see happen. The final column, third column, is effects of inhibition. That would be the results of giving an antagonistic drug. They're going to inhibit or block this normal response. So the middle column is what we expect to see happen naturally from epinephrine and norepinephrine in the body, or the effects of an agonistic sympathetic drug that is selective for this specific receptor, whichever one we're looking at. So again, when we look at Alpha-1, there's going to be some CNS stimulation, but we're really primarily focusing on blood vessels, so we're going to get vasoconstriction. Is one of the main things we get with Alpha-1 stimulation. In the GI system, we're going to... These are the sites that are telling the GI system to relax and to decrease their peristalsis. In the bladder wall, alpha-1 is the one that is going to focus on decreasing that contraction of the bladder muscle, but increasing the contraction of the sphincters. And on the pupils, alpha-1 is the one that is responsible for the dilation of the pupils. So as you go on down through alpha-2, I'll tell you it's an outlier. Its activity is primarily in the brain, not out in the periphery, not out in the peripheral muscles and tissues. So when it's stimulated, normally we think of fight-or-flight response would involve vasoconstriction and increased blood pressure. The alpha-2 action happens in the brain and it actually causes vasodilation on stimulation. So it's an outlier when we're thinking of the basic Firefly things. Beta 1, important thing for me, the easy way to remember it, beta 1 and beta 2, some of our primary sites of action are going to be in the chest. So in the chest, I have one lung. So that's beta 1. Beta 1 receptor sites are focused on the heart as well as being the ones that deal with the kidneys and looking at the renin-angiotensin system. But essentially, we're going to really focus beta 1 as being heart. So it's going to increase heart rate, also increase contractility or strength of contractions. Beta 2 stimulation, we have two lungs in our chest. So we're really focusing in on the large airways, the smooth muscle, the bronchi. So beta 2 is going to be looking at causing vasodilation of the blood vessels in the lungs, especially bronchodilation, those large airways it's going to create. It's also going to have an impact on the GI system. in terms of the motility it's going to impact the liver somewhat it's going to impact the uterus as well so it's going to have some crossover with alpha-1 on a few of those areas but again alpha-1 from the high points we're looking at when we're looking at phasoconstriction the alpha-2 because of that the fact that is working in the brain we're looking at vasodilation beta 1 we're looking increased heart rate increased contractility beta 2 we're looking at bronchodilation and again also need to be aware of those other organs how are we going to impact those on the inhibition side or antagonistic side we're basically going to block those effects so we should see the opposite kind of response so again just refresh your memory on alpha 1 alpha 2 beta 1 beta 2 where are the primary sites and what is the normal Response we would expect with stimulation and what are the normal effects we would expect with inhibition or antagonistic action of a drug. On the parasympathetic or cholinergic side, again, it's simplified. There are two receptor sites, muscarinic and nicotinic. The nicotinic is really tied into skeletal muscle and some central nervous system effects, not so much the rest and digest organs that we looked at on the previous diagram. So when we're talking about cholinergic responses, parasympathetic responses. Generally, we're thinking of the muscarinic responses. So that's all the organs. They all are muscarinic response. Muscarinic receptor sites, they're all going to respond. So if we're using a medication to deal with one specific area, we have to be aware that the other organs are going to be impacted as well. So again, the concept for agonist, the agonist site is rest and digest. So we're going to increase salivation. We're going to increase the urine output, we're going to increase GI activity, we're going to have increased secretions in general, pupils are going to constrict down, we're not that concerned about getting a lot of light in. Now the antagonist or the anticholinergic response of a drug, and that's the term we'll usually see with the antagonist in this case, will be anticholinergics. You can also think of those as sludge and putting things negatively. So S is the salivation is decreased. Lacrimation or formation of tears is decreased. Urinary retention is a possibility because, again, we're opposing that normal response that would cause us to urinate more freely. I was going to put in drowsiness and dizziness from a central nervous system standpoint. There's going to be some GI upset because we're going to slow the gut down. Things are not going to move through as quickly and as smoothly as they normally would. And our eyes, because of the decreased secretions, and in this case we'll have pupil dilation, we're going to have blurred vision and a sense of dryness in our eyes. So again, sympathetic fight or flight on the agonist side. parasympathetic or cholinergic focusing on the muscarinic and we're looking at the rest and digest type activities The next system, again, should just be a review of your anatomy and physiology. But I want to look at the renin-angiotensin-aldosterone system because it's going to work in conjunction with that autonomic nervous system side, especially the sympathetic side. When we were dealing with things like blood pressure control and fluid balances, they were canned in hand. I don't remember one of the receptor sites. on the adrenergic or sympathetic side, mentioned that it's going to increase the release of renin. That's the chemical that starts this whole process. So again, the renin angiotensin aldosterone system is really tied into maintaining the appropriate amount of fluid in and circulation. So it's going to respond to low fluid flow, a little bit low pressure. It's also going to respond to low sodium concentration because sodium is... is connected to fluid level. So if I have a low sodium level, my body is going to interpret that as I also have low fluid level. So the basic process in review is the renin gets released. At the same time, the liver is releasing this angiotensinogen, which means it's a forerunner of angiotensin. These two things are going out in the blood, the renin and the angiotensinogen, and they form angiotensin 1. When angiotensin 1 gets into the pulmonary circulation, there's an enzyme there, ACE, angiotensin converting enzyme, or ACE, that's going to cause a conversion of angiotensin 1 to angiotensin 2. That's the point we're really concerned about from this process and its impact on fluid movement and particularly on blood pressure. Once angiotensin 2 is formed and in circulation at the blood vessels it's going to cause widespread vasoconstriction. It's going to increase our blood pressure. It's going to bring it up. At the same time again the problem that the body was responding to is this sense that we have low fluid so they're going to read that as being low blood pressure. So vasoconstriction is going to help bring our blood pressure up. But the angiotensin 2 also goes to the adrenal cortex. Let me change it. It goes to the adrenal medulla. And so this slide here is incorrect. It's going to go to the adrenal medulla and cause... I'm going to back up just a bit again. Okay. As the cystole is going to stimulate the adrenal cortex to produce aldosterone. Aldosterone, the other thing that comes out of the adrenal cortex is the corticosteroids. But along with the corticosteroids, we get this aldosterone as another hormone. So we're talking about a hormonal response here. The aldosterone then goes into circulation. It goes to the kidneys, and it tells the kidneys to retain sodium. which is going to bring that sodium level back up. And by retaining sodium, we're also going to retain water, her fluid. That retaining fluid fills up our circulatory system, and that helps support increasing our blood pressure. So again, in this case, on the autonomic nervous system side, on the sympathetic, we could increase blood pressure by having an adrenergic agonist action, particularly stimulating alpha-1 for vasoconstriction, but also stimulating beta-1 to increase our heart rate and the force of our contractions. Those two things are going to drive blood pressure up. That's going to be supported by the renin-angiotensin-aldosterone system. through this conversion to angiotensin 2 which is also going to cause vasoconstriction but then it's also going to cause aldosterone to be released which is going to hold more fluid in which gives us more fluid to pump through the circulatory system and again and that result is we've brought our blood pressure up so we can see the fact that we can't talk about these systems as distinct parts that aren't related to each other so on the neurological side it's a very quick and short-term response that fight-or-flight so in the green box to the left here my body senses that my blood pressure is either low or that I have low fluid volume which is going to result in low blood pressure which is low circulation low cardiac output a lot of negative effects from there so the very quick response is the neural response so it's activates the autonomic nervous system particularly the sympathetic side Adrenal glands from the medulla, the interior of the adrenal glands are going to release the epinephrine and norepinephrine. Or again, you might see adrenaline, noradrenaline. They are going to go out and by stimulating alpha-1, they're going to cause vasoconstriction, the peripheral vasoconstriction. By stimulating beta-1, we are going to get an increase in heart rate. and an increase in the strength of the contraction, which is going to increase our cardiac output. Those two things together are going to cause an initial increase in our blood pressure, which is what we're going for. That initial signal also goes down and activates the renin-angiotensin system. It's going to be a little bit lower, but a longer responding action. So the kidneys are going to produce the renin. From the renin out in the bloodstream in the work of the angiotensin converting enzyme, ACE, we're going to get angiotensin 2. That is going to, again, go to the blood vessels and increase basal constriction, along with that alpha-1 response on the neuro side. But it's also going to cause the release of aldosterone. which is going to go to the kidneys and tell the kidneys to hold on to fluid, hold on to sodium as a way of holding on to water. That's going to increase blood volume, which is also going to bring my blood pressure up. And as the final result, we have homeostasis of fluid and blood pressure, which is what we're going to. So the two systems work together, one using a the nervous system and particularly autonomic nervous system the other using a hormonal system in this case we're looking at hormones primarily released by the adrenal glands we also have adh being released by the pituitary which is also tied into this to a degree as well so again go back and review your anatomy and physiology and your pathophysiology your fluid balance discussions in amp and make sure you're comfortable with that because As we understand what's happening in the body, it makes it easier for us to understand why the drugs that we're using, how that pharmacodynamic part of the drug makes sense. Last area I just want to touch on quickly to show that connection to is in anatomy and physiology and patho, you talked about the inflammatory response. And it's this process of how. Our body responds to any type of cellular or tissue injury. and one of the components of that is pain so that pain comes from the inflammatory process where we have increased permeability we have increased blood flow to an area because of that we can get edema we get swelling we also get mediators or chemicals that increase the sensitivity of pain receptors in the area all of this is part of the natural inflammatory response some of the stimulate Chemicals that get released are things like prostaglandin and some other mediators. All those just help continue the inflammatory response to be present for as long as our body needs it. Often that inflammatory process and associated pain especially may call for some intervention to help relieve the pain related to the inflammatory process. So when we look at pain management. particularly with anti-inflammatories, and those can be non-steroidal or steroid. Or if we look at autoimmune diseases, which are an inflammatory response that's gone bad, we're going to look at immunosuppressant or immunomodulator drugs. We are inhibiting that inflammatory response or components of it in order to get pain relief. So we just have to be aware that we are interrupting or blocking a normal response. And when we get into those drug classes, we'll talk about why is that a concern? What could possibly go wrong when we interrupt a normal response in order to get symptom relief in terms of the pain? Again, take some time, review your anatomy and physiology, particularly in these three areas, the autonomic nervous system, the renin-angiotensin-aldosterone system, and the inflammatory response. and how it functions. And with this last one, when we get into the non-steroidal anti-inflammatories, we're going to talk about prostaglandin and its role a little bit more. So this is just, again, a quick review and a quick reminder that pharmacology does not exist as a concept by itself. It is tied closely into understanding our anatomy and physiology and pathophysiology concepts. So I will talk with you on the next topic. Thank you.