Transcript for:
Overview of Anti-Hypertensive Medications

foreign engineers in this video today we're going to be talking about anti-hypertensive medications there's a lot to go over but what I want you guys to do is if you guys do benefit from this video and you guys do like it it really helps you to understand this concept please support us and I'm telling you the best way that you can do that is by hitting that like button commenting down the comment section and also subscribing also if you guys really want some amazing notes and illustrations that an engineer team has compiled go down in the description box below we have a link to our website where you guys can check that out all right without further Ado let's start talking about antihypertensives though so we talk about anti-pretense what I want to do is I want to break them into four categories okay and I want to go within these four categories I want to talk about the mechanism of action I want to talk about the drugs that are in that category and then we'll also discuss some of the adverse effects that they may have because I think it makes sense to cover them when we talk about their mechanism of action all right so these four categories is sympatholytics diuretics renin Angiotensin aldosterone Inhibitors and then lastly is your vasodilators all right sympatholytics they're inhibiting the sympathetic nervous system that's the whole concept right now we're going to go through these in a couple different ways now the first one here is we're going to talk about the centrally acting drugs so there's two Central acting drugs that I want you guys to know and these two Central acting drugs are called clonidine so one is called clonidine and the other one is called Alpha methyl dopa now these two drugs are really interesting okay what do I mean by they're centrally acting you see these nerves coming from the thoracic part of the spinal cord this is your sympathetic nerves and the sympathetic nerves that go from the thoracic part of your spinal cord they actually go and release norepinephrine onto the heart and onto the blood vessels right and whenever they release norepinephrine onto the heart we know that it increases heart rate it increases contractility we'll talk about that a little bit in a second it also works on the arteries to squeeze the heck out of them and increase resistance and it squeezes the veins to increase blood return to the right heart so all of these things are working to in general to increase blood pressure in that concept well if I give a drug that has the ability to maybe suppress the Central Drive that causes the sympathetic nervous system to release norepinephrine so here's these thoracic spinal cord nerves they're releasing from these nerves lots and lots of norepinephrine and the norepinephrine work on the heart and it'll work on the blood vessels and what it's designed to do is this Central process here is that when you have an increase in norepinephrine it's going to increase heart rate it's going to increase contractility it's going to increase systemic vascular resistance and it's going to increase preload and all of these things if you think about it you increase heart rate you increase cardiac output you increase contractility you increase cardiac output you increase resistance you increase blood pressure you increase preload you increase cardiac output and then we know that the formula is that blood pressure is equal to cardiac output times systemic vascular resistance you increase resistance you increase blood pressure you increase cardiac output you increase blood pressure so what I need to do is I need to give a drug like these ones quantity and Alpha methyl dopa and what they will do is they have the capability of inhibiting all of these processes they can relax the arteries that reduce the systemic vascular resistance they relax the veins that reduces preload they can inhibit the actual heart from beating fast and Contracting fast that will reduce the heart rate and contractility all of these things will reduce cardiac output reduce systemic vascular resistance and reduce blood pressure now you're probably wondering okay they do that but how these nerves when they release norepinephrine onto the heart and the blood vessels they work through particular processes right we already talked about that but here in the central nervous system there's this Central Drive for the sympathetic nervous system so what I want to do is I want to take like this particular area here and I kind of want to zoom on because this is the thing that's really driving your sympathetic flow so if I have an ability to inhibit this process right here I may lose the sympathetic flow or outflow to the heart and the blood vessels right so let's say that we take that and we zoom in on it okay so this right here is going to be this type of interaction now here this neuron has vesicles containing norepinephrine and when this nerve is stimulated right it fuses with the cell membrane and starts plucking out norepinephrine into the synapse norepinephrine will then bind onto these receptors and then stimulate flow via the sympathetic outflow so it'll stimulate sympathetic nervous system outflow now imagine I give a drug like Clonidine continent is really interesting because what clonidine will do is it'll bind onto these receptors on the synaptic terminal these are called Alpha 2 receptors clonidine is a alpha 2 receptor and Agonist so it's going to stimulate the Alpha 2 receptor now you're probably like okay that's interesting when this clonidine stimulates the Alpha 2 receptor so it's going to stimulate this particular receptor this receptor is responsible for inhibiting norepinephrine from fusing with the cell membrane then what happens to the norepinephrine that gets released it reduces what happens to the stimulation of the sympathetic nervous system it becomes inhibited you lose the sympathetic outflow if you lose the sympathetic outflow what happens to the norepinephrine released towards the heart it's reduced what happens to the ability to stimulate the heart rate you lose that you inhibit the actual heart rate from going up you inhibit the contractility what happens to the outflow on the arteries you lose the ability to constrict so they relax and what happens to the venal constriction you lose it so therefore it relaxes and you see how this drug has the ability to do all of these things now quantity and is believe it or not even though you would think holy son of a gun it does so many things it has to be like a first-line agent believe it or not it's not a first-line agent it's not commonly utilized to be honest with you it's more of like a third line agent if you really need it the real true indication of why we would use the struggle we talk about a lot more in the adrenergic Agonist lecture is that this is good for kind of like a patient who has withdrawal symptoms so the patient who's just recently been on a bender on alcohol benzos or some type of other situation like um usually alcohol benzodiazepines are the big ones that are usually the primary problems are opioids and they withdraw and when they withdraw they develop a massive tachycardia they develop hypertension they squeeze on their blood vessels so if I give this drug when I actually inhibit that sympathetic outflow I could treat the withdrawal symptoms so that's the true really only indication of when we would give clonidine is that this drug can really be good and situations of withdrawal symptoms so withdrawal and particularly withdrawal from specific medications because what this does is when you withdraw you have a massive sympathetic outflow because you've been suppressing that outflow with depressants like alcohol such as benzodiazepines such as opioids and when you remove that suppression now you have nothing but sympathetic outflow and so you can inhibit that by giving clonidine that's the really the only true indication but because it has the ability to suppress your central kind of norepinephrine drive it also may lead to sedation so one of the adverse effects to watch out for with clonidine is watch out for Sedation it can make the patient a little bit more sedated all right Alpha methyl dopa doesn't actually work through the Alpha 2 receptors what it does is Alpha metal topa is an interesting drug here so imagine here's Alpha methyl dopa it goes through the pathway that's used to make norepinephrine and what it does is it actually inhibits you from actually truly making norepinephrine so in order to be able to make norepinephrine you know any tyrosine and then l-dopa and then dopamine and the norepinephrine the alpha methyl dopa kind of Alters the synthesis of norepinephrine and so then you have less norepinephrine in these vesicles less norepinephrine released and less sympathetic outflow because of that so it's a pretty interesting drug and really the only indication of why we would give this drug we'll talk about a little bit later is pregnancy uh one particular thing that is weird with this drug is that it may actually cause a positive Coombs test and so you may see that if a patient develops like a little bit of anemia and you send off a what's called a Coombs test they may come back Coombs test positive which may make you think about an autoimmune hemolytic anemia but this is one particular category of drugs so one category of drugs for the sympatholytics I'm going to put here let's do it in pink so that we see it here is your central acting drugs and again this is Clonidine and Alpha methyl dopa they work to suppress they're working right here to suppress the central sympathetic outflow so they reduce the norepinephrine being released on the heart and on the blood vessels so it inhibits heart rate inhibits contractility inhibits arterial vasoconstriction and inhibits venal constriction all of these things do the following that's the whole concept here because we're inhibiting this massive release of norepinephrine all right beautiful let's come to the next part of the drugs for some patholytics the next thing is that we have beta receptors that are present on the heart we know that that's the primary receptors right so if we look here let's say that these are these sympathetic neurons right here so these are the sympathetic neurons and again what are they pumping out here they're pumping out what type of molecule noro epinephrine so they're pumping out norepinephrine and you know there's another molecule another technically hormone neurotransmitter that's also released from the sympathetic nerve system it's epinephrine because your sympathetic nervous system also stimulates the Adrenal medulla and pumps that up in effort but nonetheless norepinephrine is released from these nerves when norepinephrine is released from these nerves onto the heart in order for them to exert their effect they need a particular receptor you know what this receptor is the son of a gun that's an interesting receptor this is the beta receptors what are these receptors here these blue little things popping off of these cells are called beta 1 receptors what is this one this is a beta one receptor in order for norepinephrine to exert its effect so we already inhibited norepinephrine release the central suppression which inhibited norepinephrine release that was these two drugs but what if norepinephrine is still released how can we block its effect on the heart so we can give particular drugs that will block the beta 1 receptor they'll bind onto the beta 1 receptor and prevent norepinephrine they'll be like hey get out of here you can't bind here what are those drugs not hard to imagine here the second category of drugs that we're going to be discussing here let's put them over here second category of drugs is going to be beta blockers but I want to be very very specific okay so beta blockers and really these are cardio selective so mainly these are primary beta 1 blockers now what these drugs will do is if we take the two cells of the heart so we have here your SA node your AV node your bundle of hiss your bundle branches and then um from there we go into your purkinje system right all of those things are controlling your the conduction of electrical activity on those cells these black cells here on the heart that's your nodal cells they have beta 1 receptors and then here on the red cells here the contractile portion the ones that actually squeeze and pump blood out of the heart those ones also have beta 1 receptors so if I give a beta blocker what I'm going to be doing is I'm going to block norepinephrine from being able to exert its effect I'm going to put produce an opposing effect I'm going to inhibit the nodal cell from being able to fire and what that's going to do is that's going to suppress the patient's heart rate that's going to drop there cardiac output and then subsequently it's going to drop there blood pressure oh man that's good I'm going to also give this particular drug these beta blockers so this is going to these beta blockers will inhibit the nodal cell from firing but it'll also inhibit the actual contractile cell from squeezing so then because of that you decrease contractility and if you decrease contractility what you know about that is that that drops stroke volume and then subsequently cardiac output and that drops blood pressure so this is the way that we could treat a patient's hypertension by reducing the amount of blood that actually leaves the heart and that would be the job of these beta blockers now there's many different agents here some of these that are very particular that I want you guys to know is what's called Atenolol so Atenolol is a commonly utilized one another one is called a bisoprolol bisoprolol another one is called esmolal very commonly utilized one especially in IV formulations and hypertensive emergencies and another one is called metoprolol now these are the most commonly utilized ones that you're going to be seeing particularly for the beta 1 blockers there is other ones that are non-selective like propanolol and natalol but we don't commonly utilize that in that particular situation they do have some beta 1 block K but I want you to remember these primary ones here okay that's our beta blockers now one of the things I want you to think about here don't be confused with this these drugs we're going to talk about they're very commonly used in a lot of comorbid conditions but if I'm giving a drug that has the ability to drop the patient's heart rate what's a potential adverse effect out of this it's not hard to imagine my friends adverse effects that you really want to be careful with with these drugs is that you can drop the heart rate down too much what is that called bradycardia so watch out for bradycardia for these particular drugs the other thing that you want to be careful of is that they can really drop your contractility and so if they reduce the contractility they can actually drop the patient's blood pressure where you really if a patient already has a weak heart and it's not getting a good cardiac output and then you drop the cardiac output even more by dropping their contractility that could put them in at risk of cardiogenic shock and that's the patients who have weak Hearts already so watch out for hypotension with the potential of it even causing shock and what patient population watch out for this in patients with decompensated heart failure I'm going to dhf decompensated heart failure do not give this to these patients you will kill them potentially all right the other thing with these drugs you know what a patient's hypoglycemic you know when they're hypoglycemic so let's say that your sugar drops down to like 25 right okay and when your sugar drops naturally what your body does is says hey hey sugar's low my cells ain't feeling too well and so because of your sympathetic nervous system goes into hyperdrive and it tries to let you know hey man something is not right and it makes you tachycardic it makes you a little bit kind of diaphoretic and so it makes you aware that something is not right and then you should check your sugar levels if you have diabetes when you give a beta blocker you block the tachycardic the hypertensive you block the diaphoretic type of response that sense of impending doom all of those things that come from the sympathetic response from hypoglycemia you don't have and so because of that this can really blunt that effect and so you want to watch out for what's called hypoglycemia unawareness okay beautiful beautiful all right that's our beta blockers okay the next category here is if we look here on the arteries and on the veins they have another type of receptor so here this is your arteries here so I'm just going to denote that this is going to be the arterial system coming from that left heart and then here is going to be the venous system going back to the right heart what I want to do is I want to take some particular cells from the vein a particular cells from the artery and zoom in on them here so here's an arterial smooth muscle cell here's a venous blue muscle cell and remember they all have sympathetic innervation we talked about that this is those adrenergic neurons and what are they pumping out what are they pumping out again I've already told you this you guys should know this right norepinephrine they're pumping out norepinephrine so we suppress the norepinephrine release from clonidine Alpha methyl dopa there is other drugs out there we just don't use them called Reser Pine and there's some other ones out there as well that we just don't use in the ganglion blockers Etc but if we inhibit the norepinephrine release all right that would be the quantity Alpha metadopa we can block the beta 1 receptors guess what guess what these receptors are on the arteries and veins Alpha One receptors these are called your Alpha One receptors that are present both on the arterial smooth muscle cells and alpha-1 receptors present on the venous move muscle cells so if I give a drug guess what this drug category would be alpha blockers man we good so if I give a drug category like an alpha blocker what's the benefit of giving alpha blockers so alpha blockers is going to be my third category of drug okay third category drug alpha blockers are going to be interesting because if I give a drug like an alpha blocker what they're going to do is they're going to block the effect of norepinephrine and epinephrine from binding on to these alpha 1 receptors on the veins and on the arteries the effect on the artery is that you're going to relax the smooth muscle it's going to inhibit the smooth muscle from Contracting right it inhibits the GQ process and because of that it'll actually cause the muscles to relax if they relax the entire vessel will undergo vasodilation so if it relaxes and undergoes vasodilation and if it vasodilates it drops your systemic vascular resistance and that will subsequently drop your blood pressure based upon the equation that we just talked about here mama that's one way the other one is the venous smooth muscle I can inhibit this one so I can inhibit this one from Contracting and I can inhibit this one from Contracting so I'm going to block my nephron epinephrine binding here and that's going to cause this one too same thing it's going to relax this is going to Vino dilate but here's where it's different when veins dilate these are supposed to now naturally think about whether they do any squeeze when they squeeze they pump blood up into the right heart which improves preload the amount of volume that's coming to the right heart or the heart in general during diastol during diastole if I relax it what happens to my my preload I drop it if I drop my preload I'll subsequently drop my cardiac output and if I drop my cardiac output I'll drop my blood pressure oh man so alpha blockers have the ability to drop your systemic vascular resistance which can drop your arterial blood pressure and Vino dilate which will reduce the preload to the heart and reduce the stroke volume cardiac output and drop the blood pressure what are some names of these particular drugs alpha blockers so here's the thing with alpha blockers there's actually two types there is selective selective and then there is uh let's call these non-selective selective now with the selective types selective types this is going to be those ones that only block the alpha one they only block the alpha-1 receptor non-selective means it could buy it could actually inhibit the Alpha One and the alpha two receptors okay The Selective ones are going to be things like prizes in terrazasin doxazosin things of that nature they usually end in the zosin okay there's also tamsulosin as well but these are particular drugs that we can give now here's what I want you to think about when you give these particular drugs that really dilate the arteries okay they dilate the arteries when you dilate the arteries what's it going to do to your systemic vascular resistance we already talked about this we said that when you dilate you reduce the systemic vascular resistance now what's really interesting about this is when you drop BP there's a there's kind of like a natural reflex do you guys know that that whenever you actually have a drop in blood pressure what this does is that stimulates your baroreceptors that goes and sends the signals to your medulla your central nervous system says hey hey BP is low we got to increase that heart rate and it sends an increased sympathetic outflow which increases your heart rate what is that called that's called reflex tachycardia so these patients who have arterial vasodilators watch out for what's called reflex tachycardia as a response to dilating the arteries and then reducing resistance reducing blood pressure creating a reflex compensatory tachycardia the non-selective agents these are going to be interesting drugs we don't commonly utilize these I've talked about them in the adrenergic antagonist lecture but this is going to be phentolamine so phentolamine and phenoxybenzamine if you guys remember we briefly talked about these the true indications of why you would really give these is if a patient has a hypertensive crisis so if they have a hypertensive crisis and it's really secondary to something like what's called a theochromocytoma or it's due to a monoamine oxidases that are in monominoxidase Inhibitors plus they're taking like tyramine from like cheese or wine you guys know all that stuff we we could potentially utilize these drugs to be able to treat that process however there is other drugs that you can utilize in those situations but that's the big things to think about with your Alpha blocker so so far we have centrally acting clonidine Alpha methyl dopa okay we have beta blockers cardio selective they primarily inhibit the beta 1 okay and that's going to be these particular drugs here and then we talked about the alpha blockers now one more thing one more thing when you actually dilate veins here's another potential complication so one potential adverse effect here is reflex tachycardia from dilating the arteries but what if you dilate veins when you dilate veins here's another interesting thing when you dilate veins another thing is that you reduce your preload okay when you Vino dilate when you reduce preload you reduce stroke volume cardiac output and reduced blood pressure what's interesting about this is that if a patient who is very preload dependent an older individual who goes from a seated position to a standing position or goes from a supine to a seated position when they move they automatically have a fluid shift where blood should increase and go back to the right heart improve their preload their cardiac output their blood pressure but if those patients who you just took away their preload dependency because you Vino dilated them now when they go to get up they have no blood coming to their right heart because you dilated them you reduce their venous return so you drop their cardiac output and you drop their blood pressure and they develop oh orthostatic hypotension so watch out for that for the Vino dilation effect so this would be from the Vino dilation effect where you can cause ortho stasis beautiful okay you thought we were done or not there's one more one more category here that's really interesting here this one we're going to sneak here in the middle and this fourth category Believe It or Not we've already discussed and this is a mix blocker this is a mixed blocker so these are alpha and beta blockers so they have the capabilities of blocking the alpha receptors in the arteries and veins they also have the ability to block the beta receptors on the nodal cells in the contractile cells so they have all of the similar types of effects they may have these potential adverse effects they may have these potential adverse effects generally not the reflex tachycardia why because they suppress the actual heart rate so generally you may see bradycardia not as common to see The Reflex tachycardia from these two agents all right so there's two particular agents here for the alpha blockers and beta blockers one is called labetalol and the other one is a really interesting drug called Carvedilol these are two particular agents that we can give and again you're going to see all the same similar side effect profile more particularly the bradycardia you can see hypotension right because it can really drop the patient's blood pressure because like a vasodilate and beta block and it can cause hypoglycemia and awareness on top of that it may cause a little bit of orthostasis but there's one more thing these they can bind to beta 1 and beta 2. so because they combine onto beta 2 guess what's a potential adverse effect my friends it can bind onto the beta 2 receptors and the bronchials on the bronchial smooth muscle and when it binds onto the beta 2 receptors and the bronchial smooth muscle guess what it can do it can cause bronchospasm so there's beta 2 receptors and labetal on Carvedilol don't mind that binding that one and if you stimulate that one you will cause Bronco spasm sorry so generally sorry beta2 receptors if you stimulate them they'll actually bronchodilate but these are beta blockers so they'll inhibit the beta-2 receptor and if you inhibit the beta-2 receptor you lose the ability to bronchodilate and therefore cause bronchospasm so this may be another adverse effect that you would see from Carvedilol or labetalol not as much so from metoprolol asthma lobosoprolol or Atenolol okay we've talked about sympathalytics a lot so far let's come down talk about diuretics and how they also are utilizing hypertension what are those drugs and some adverse effects all right so next category diuretics now diuretics are really interesting and why would we use it you're probably exactly why would I use it for hypertension we'll talk about why we would use them but there is three particular categories of diuretics now the whole basic concept of why we would use diuretics in the treatment of patients with hypertension is relatively straightforward and the concept of it is is that when you give a particular diuretic what a diuretic is doing is it's inhibiting sodium and water retention so it's really inhibiting the kidneys from being able to retain any sodium and water so any of the sodium there's going to be less sodium and then subsequently less water now you're probably like okay why is that potentially beneficial well now that I actually went and I peed out a lot of this sodium and water so now I peed out lots of sodium I peed out lots of water lots of this is in my urine now I'm going to effectively decrease the amount of sodium and water within my bloodstream what is that equivalent to that's equivalent to blood volume so now by giving a diuretic I'm going to decrease my blood volume if I decrease blood volume I decrease the amount of blood that is able to be returned to the right heart therefore I reduce preload because I'm reducing my venous return if I reduce preload I reduce stroke volume and cardiac output and I have reduced stroke volume cardiac output I reduce blood pressure and so you see why this may be potentially beneficial and really the only situations where it would be beneficial is if the blood volume is like really high and what kind of conditions would blood volume be high that actually you may benefit from pulling some of that sodium and water off really volume overload States and so you may find that the true indication of giving these particular drugs these diuretics may be beneficial in patients who are volume overloaded so it may be indicated in a patient who has some type of congestive heart failure or they have volume overload which is iatrogenic so maybe they've been in the hospital for like you know a couple days and they've gotten like crushed with 20 liters of fluid in that situations these may be particular drugs that we could give to pull some of the sodium pull some of the water out of the actual blood and then reducing blood volume reducing preload cardiac output and lowering blood pressure again we'll go over some more indications later but I just want you to get the basic concept of why that could potentially be beneficial now the basic mechanism of action we're going to cover we're not going to go into detail because we're over that in the diuretics lecture but the basic concept here is that when you give a diuretic there's three particular diuretics one category here we're going to put this one here first one category is called your thiazide diuretics so here's one category first first one is your thiazides now thiazides there's a couple different drugs and we'll talk about them but what here's the basic concept when you filter fluid across your glomerulus it should move down through this part the descending limb of loop of Henley then up the ascending limb with Loop of Henley and then it gets What's called the distal convoluted tubule so right here when fluid is passing through the distal convoluted tubule there's particular channels here that reabsorb sodium and reabsorb chloride so they work to potentially pull sodium and then subsequently it'll pull water into the bloodstream when I give thiazides what thiazides are going to do is they're going to inhibit these channels and now me being able to bring sodium into the bloodstream is reduced and then subsequently the pool of water is reduced and then what happens I pee out tons of sodium chloride and water and that's the whole concept here is that I'm reducing the sodium in water which will subsequently reduce the blood volume the preload the stroke volume the cardiac output and the blood pressure what are these drugs these are hydrochlorothiazide there's also chlorothiazide there's chlorthalidone chlorthalidone and another one that's a really interesting one is called metolazone so these are the drugs that we could consider thiazides now they're really good at hypertension and believe it or not they happen to be one of the first line agents for hypertension and that's a really cool concept here they're actually really really good and uncomplicated essential hypertension and any kind of category where the patient be uh you know generally younger and have really no other particular problems it's a pretty good drug if they have CHF it actually can provide an extra benefit as well are another drug category is another interesting one it works here so we have the distal convoluted tubule via the thiazides the other one over here the second category of drug is another one that we can utilize and this is called a Loop Diuretics so these are your Loop Diuretics now the Loop Diuretics there's a couple of these but what they do is here at the ascending limb so here's the fluid it's running through the ascending limit of the loop of handling generally there's a sodium potassium two chloricotransport that pulls massive amounts of sodium and pull massive amounts of water across the kidney tubules and into the bloodstream well if I give a loop diuretic what it's going to do is it's going to inhibit the sodium chloride sodium potassium to chlorideco transporter and I inhibit the sodium and water reabsorption I drop the blood volume the preload the stroke volume cardiac output and the blood pressure what kind of drugs are there here these could be Furosemide furosemide this would be bumetanide this would be torsomide these are very very commonly utilized drugs particularly in patients who have CHF now thiazides are really good for essential hypertension so it is important to remember this is going to be out of all the diuretics the one that we would likely use for hypertension is going to be this one this is likely going to be your first line agent out of all of that diuretics you really won't go to Loops the loops are mainly going to be patients through or like completely informantly volume overloaded and have CHF and you're giving it more for the symptom control you're trying to treat their hypertension but they're so volume overly you pull that volume off you'll pull their blood pressure down that's really the true only indication for loops now these drugs have similar side effect profiles again we'll go over them in the actual diuretics lecture but for right now since they pull lots of sodium since they pull chloride into the actual urine what would you see as a potential adverse effect from both of these you can see hyponatremia you can also see that when you pull sodium you also pull potassium and protons and so from these drugs you can also see hypokalemia and you pull protons so you can also see metabolic alkalosis as another potential adverse effect so you can also see metabolic alkalosis the other thing here which I'll talk about briefly is that they both inhibit uric acid excretion of the proximal convoluted tubule and so because of that they can really bump up your uric acid levels and so you want to watch out for this don't give this to people who got a big old hot big toe from gout okay because this can really bump up your uric acid levels Loop Diuretics Also may jack up the ear too so watch out for ototoxicity but again we'll go over all of these in more detail in the diuretic lecture all right the last category here of diuretics is the third one here and this is an interesting one so this is called aldosterone antagonist so you're probably like wait aldosterone I thought exactly we were going to talk about aldosterone and the Renaissance aldosterone symptoms Inhibitors we will but this one also acts as a diuretic so let's talk about it so this one is your aldosterone antagonist now this one does have diuretic capabilities but it's really important to remember that it is extremely mild so it's not a super great diuretic but what they're going to do is at the same point of the distal convoluted tubule there's also receptors okay there's receptors that from aldosterone so aldosterone has the ability to act on intracellular receptors that are present in these distal convoluted tubular cells it's actually just draw it right here here we're going to say that this is a distal convoluted tubule cell right here is these channels here sodium chloride channels aldosterone antagonists will actually work here's aldosterone it'll bind onto a receptor and that'll actually activate particular enzymes that'll synthesize these particular channels that pull what sodium and pull water into the bloodstream if I give a drug like an aldosterone antagonist what it'll do is it'll inhibit aldosterone from being able to bind onto the receptor inhibit the synthesis of these Transporters and inhibit sodium and water reabsorption dropping blood volume dropping cardiac output dropping blood pressure now these drugs are going to be things like apler known and this is also going to be things like amyleride and another one called spironolactone and these drugs again not super powerful hypertensive agents but they can be utilized to reduce mortality in patients with CHF one of the big things to watch out for with these drugs and we'll probably recap it a little bit later is that because they inhibit aldosterone industria not only reabsorbs sodium and water it excretes potassium so you inhibited the excretion of potassium so potassium can actually go up it's the only one that actually spares potassium so watch out for hyperkalemia with this particular drug and then with spironolactone it can actually cause the blockage of multiple other androgens so sex hormones and so this may lead to the effect of gyneco mastia so watch out for gynecomastia with spirano lactone all right my friends that covers the diuretics so we've covered this in patholytics we've covered the diuretics now let's move on to the next category which is the rain and Angiotensin aldosterone synthesis Inhibitors all right so renin Angiotensin aldosterone synthesis Inhibitors man it's a mouthful with these particular drugs how do they work to treat hypertension well we've got to briefly go through the pathway all right kidneys they make a very special molecule called renin now your question that should be popping out there is well what actually triggers random production Zach ah great question so on the actual kidney there is special receptors called beta 1 receptors right so there is beta 1 receptors that are present on these cells in the kidney called the juxtaglomerular cells and when stimulated stimulated by what the sympathetic nervous system so the sympathetic nervous system can release what type of molecule here noro epinephrine that'll act on these beta-1 receptors and start pumping out renin that's one particular mechanism the second mechanism that actually causes random production here is that whenever a patient has low renal perfusion so if there is a very poor perfusion to the kidneys so a decreased perfusion so a decreased perfusion maybe this is due to a decreased cardiac output so there's a reduced perfusion to the kidneys this can also stimulate the juxtaglomerular cells to pump out renin but either way renin is being made when Raiden is made and it's made in a lot it interacts with a very special molecule made by the liver what is this molecule called This is called angio tensinogen now Andrew tensinogen is made by the liver what happens is renin when it's made it acts on angiotensinogen and what it does it actually takes angiotensinogen and converts it it stimulates this it runs an enzyme and it stimulates angiotensinogen by cleaving off a couple amino acids and turns it into something called Angiotensin one now Angiotensin 1 then goes to the lungs in the capillary endothelium of the lungs there is this special cool enzyme what is this enzyme this enzyme is called angio tension converting enzyme this enzyme is a very powerful enzyme and what it does is it takes Angiotensin one Cleaves off a couple more amino acids and then synthesizes something called angio tencent II so let's actually do it like this let's actually say here's Angiotensin one it'll run through here and it'll pop out here after it interacts with this enzyme into Angiotensin II which is in the lungs now what happens here Angiotensin II then goes and acts on varies different tissues various different tissues one is it can go over and act on the heart tissue it can also come here and act on the adrenal cortex it can also come here and act on the central nervous system it can also come down here and we'll talk about this a little bit later I'm just going to draw a couple dotted lines but it has the ability to come down here and work on special parts of the kidney tubules as well and exert many different effects that can work to increase the patient's blood pressure let's talk about that all right so now Angiotensin II is made right it's synthesized okay once Angiotensin II is made it then goes and it works on blood vessels and it's really powerful very very powerful so here is the artery right here's an artery of our coronary of our vascular systemic circulation and here's the vein now normally again the artery if we take a piece of a cell here and actually zoom in on we're going to see this piece of a cell here we're going to zoom in on so here's a arterial smooth muscle cell and here's a venous smooth muscle cell on these they have a very special type of receptor this is called an angio tensin II receptor so this is an Angiotensin II receptor when Angiotensin II binds onto this particular receptor it produces a very profound load of ions positive ions into these actual smooth muscle cells which causes an intense contraction and when it causes this intense contraction of the actual smooth muscle cells it does what well naturally it'll cause the vein to squeeze like a son of a gun so here we're gonna have two Pathways here this is going to be the normal pathway by Angiotensin so for the arterial pathway this is the normal pathway when Angiotensin II is high it'll actually cause vasoconstriction so if it causes Vaso constriction it'll really cause the blood vessel the actual blood vessel diameter to decrease and that really pumps up your systemic vascular resistance and that really pumps up your blood pressure so your blood pressure goes up intensely on top of that it also works on the venous smooth muscle cells and when it works on them it actually causes Vino constriction and if you these venal constrict these poppies you're going to really push a lot of blood where into the right heart and so it increases your preload and if you increase preload you increase stroke volume cardiac output and subsequently you increase blood pressure so that's one way that Angiotensin II can directly increase our blood pressure is by squeezing the heck out of the arteries and squeezing the heck out of the veins increasing resistance increasing preload and subsequently increasing blood pressure okay another thing Angiotensin II can do is it can act on the adrenal cortex and the adrenal cortex will then start pumping out a very special type of molecule this molecule is called aldosterone you're probably wondering where did the aldosterone come from before when aldosterone is actually synthesized it's synthesized because Angiotensin II is stimulating the adrenal cortex to pump it out so now it's going to be stimulated here aldosterone will then work its way down to the actual kidney tubules and when it gets into the kidney tube is what it does is remember I told you it acts on specialist receptors that increase sodium and chloride Transporters on the tubular Lumen and because of that you can pull more sodium and water into the bloodstream so the effect here is that you're going to yank more sodium and more water into the bloodstream so the effective process here is of increased sodium it'll increase water and that will do what that'll increase your blood volume and we know that if we increase blood volume we increase preload we increase stroke volume cardiac output blood pressure yada yada that's one effect okay it also we'll talk about this little effect here later that we're gonna actually let's just do it now let's just do it now here I'll dot Angiotensin 2 can also come over here now it does work here again to stimulate the zone glomerulosa to make aldosterone increase sodium water reabsorption increase blood volume but it also can act over here on the arterial system so you know blood going into the glomerulus this is your afferent arterial so this artery here and then leaving the glomerulus this part here is your efferent arterial there's lots and lots of Angiotensin II receptors that are present on the efferent arterial and you're probably wondering like why all right all right well I got you so here on the efferent interior there's a lot of Angiotensin II receptors when Angiotensin II binds on to these receptors and efferent arterial it squeezes the heck out of them if you squeeze so imagine here I'm going to squeeze on this efferent arterial what do you think is going to happen if I have Angiotensin 2 here and I squeeze I bind onto these efferent arterial receptors I squeeze them I vasoconstrictor what's going to happen to the pressure so imagine you have like I'm squeezing here and blood is supposed to be leaving the glomerulus and going into the affair materials now it's being occluded the pressure in the glomerulus is going to shoot up because of that if I stimulate this thing if I vasoconstricted guess what's going to happen I'm going to increase the glomerular blood pressure if I increase the glomerular blood pressure I'm going to subsequently increase the glomerular filtration rate I'm going to increase protein to be lost protein loss and I'm going to thicken the glomerular basement membrane these are the three problematic issues with this because if the pressure in the glomerulus is super super high it's going to cause you to now push tons of fluid which is going to be fluid and proteins into the actual convoluted tubular system so that's going to cause a massive GFR massive protein loss but it's also going to put a lot of injury on the glomerular base membrane from high pressure and it can thicken it and progress patients to chronic kidney disease oh man it's the son of a gun that's Andrew turns into okay so one thing is it squeezes arteries veins it then increases aldosterone which increases sodium water reabsorption it causes efferent arterial vasoconstriction which increases interglomerular blood pressure increases GFR increases protein loss and thickens the glomerular basement membrane what else can this son of a gun do don't worry there's more it also tells the posterior pituitary to pump out what's called antideretic hormone antideretic hormone will then work its way down to the actual kidney tubules at the collecting duct so here's the collecting duct this one worked here aldashin at the distal convo to tubule but what ADH does is it actually works on aquaporins it increases the expression of aquaporins which pulls and Yanks water into the bloodstream so it increases water reabsorption and if you increase watery absorption you increase blood volume now again we're seeing an effect of an increase in blood volume so with the combination of aldosterone and ADH what you're seeing here is with ADH and with aldosterone is you're seeing a really interesting combo here you're seeing that they're working on the kidneys to retain sodium and water and so because of that they're going to do what they're going to pull more sodium and water into the bloodstream that's going to increase sodium water reabsorption that'll increase blood volume that'll increase preload that'll increase stroke volume and cardiac output and that'll increase the patient's blood pressure you're like Zach okay I thought that we were supposed to talk about antihypertensives in this dang lecture we are but now we know exactly how these antihypertensives are going to work now for this system let's come up let's talk about the drug categories because there's three of them that I want to go through first one is going to be starting here at the ace then we'll come down here and talk about the Angiotensin II receptors and then we'll finish off with aldosterone antagonists briefly recapping because we already talked about it all right so the first category of drugs now there is one drug up here that you technically do have a drug that it can inhibit renin it's called Alice Chiron but it's just not utilized we don't utilize you theoretically it seems like an amazing drug but we just don't use it so Alice Chiron is one of those drugs but I'm not even going to write it down because again it's not a drug that you're really ever going to see or prescribe a drug that you will see and will prescribe is ACE inhibitors okay so these are very commonly utilized drugs so ACE inhibitors is going to be one of these types of drugs in the renin Angiotensin aldosterone blockers so what is this drug category here this is going to be your ACE inhibitors your Angiotensin converting enzyme Inhibitors these are really really good drugs I really like these drugs and one of it sounds a little weird when I say I really like drugs but this drug here is you remember the prills all right so this is like Lisinopril this is a really commonly utilized one I actually common I prefer captopril as well this is a really good one um there's also um another one called benzopril um and then there is also enalapril there's a lot of these men out there so there's a lot of different just remember the prills okay now with these particular drugs you're wondering how do they actually help with hypertension right okay what they do is these drugs these ACE inhibitors they're inhibiting the ace enzyme if they inhibit the ace enzyme they inhibit Angiotensin 1 being converted into Angiotensin II so they subsequently drop the angiotensin two levels if I drop the angiotensin two levels my friends tell me tell me please what is the overall effect of this the overall effect of reducing Angiotensin II is that I'm going to reduce arterial vasoconstriction I'm going to reduce Vino constriction I'm going to reduce aldosterone oh my gosh there's so many things I'm going to reduce ADH production I'm going to reduce the glomerular blood pressure all of these things are going to be helpful so I'm going to reduce the patient's arterial vasoconstriction that's going to reduce the resistance reduce their blood pressure I'm going to reduce Vino constriction that's going to reduce preload reduce stroke volume critical blood pressure I'm going to reduce our Dash from reduce sodium water uh ADH reduced water reabsorption reduce blood volume preload stroke volume cardiac output and I'm going to reduce the glomerular blood pressure preventing GBM thickening preventing protein urea preventing an increase in GFR now that may be interesting right we'll talk about that a little bit why would you want to drop the GFR that's one of the potential downsides that you can actually see or an adverse effect of these drugs we'll get to it a little bit later one big thing with these drugs okay is aces not only convert Angiotensin 1 to angiotensin two let's see let's do this in this beautiful color here okay there's a molecule called bradykinins Brady kindness now bradykinins are these very interesting like little molecules kind of like little inflammatory mediators if you will and they're supposed to be acted on by the Angiotensin converting enzyme into like these different inactive metabolites that don't have that type of inflammatory nature to them if I give an Ace inhibitor I inhibit the conversion of bradykine into the inactive metabolites and so what happens to the bradykinin levels they go up if bradykinin levels go up the problem with this is two potential things one is that elevated levels of bradykinin can actually cause agitation of cough receptors and so this will cause patients to have a nasty low cough it also can cause an increase in inflammation so it can cause a little bit of vasodilation of the pulmonary blood vessels or the bronchial blood vessels and cause capillary leakage so it may cause inflammation particularly if some of the upper respiratory tree and low respiratory tree so this may cause angioedema so watch out for these things which you're going to see way more commonly with ACE inhibitors than you will with the other drugs within this category so there's a lot higher risk of dry cough and angioedema due to alternating altering the bradykinin pathway all right beautiful okay the next drug category is the aldosterone and I'm sorry the Angiotensin II blockers or the Angiotensin II receptor blockers so let's talk about this drug category here so the second drug category that I want to mention here the second drug category and I often find me I am very fond of these ones as well is your angio tencent to receptor blockers your arbs your arbs these drugs there's a lot of these lazartan Valsartan candazartan lots of these particular medications but the basic concept here is that these drugs Angiotensin II receptor blockers will bind onto all of the receptors that Angiotensin II binds onto so everywhere that Angiotensin II receptors are going to bind everywhere Angiotensin II binds onto a particular receptor it's going to inhibit it so what would that do let's come down and take a look at what that would do so what would it do think about it Angiotensin II binds onto the Angiotensin II receptors on the venous smooth muscle and the arterial smooth muscle smooth muscle so it's going to inhibit it on these two particular sites so what's that going to look like it's going to inhibit venal constriction and it's going to inhibit arteriolar vasoconstriction so it's going to again inhibit Angiotensin angiotensin two blocking and so that will again reduce arterial arterial vasoconstriction that'll reduce systemic vascular resistance it'll reduce Vino constriction that'll reduce preload that'll reduce your cardiac output your blood pressure what else it also will inhibit the aldosterone release so it'll block these particular receptors and it'll block ADH from being able to be released so it'll reduce ADH it'll reduce aldosterone what's the overall effect of these two particular things if you inhibit aldosterone you inhibit sodium and water reabsorption if you inhibit ADH you inhibit water reabsorption this inhibits the increase in blood volume this inhibits the increase in preload stroke volume critic output and what else you also inhibit Angiotensin II from being able to bind onto the Angiotensin II receptors on the efferent arterial that's going to lower the glomerular blood pressure that'll then reduce the GFR reduce the protein loss and reduce the thickening of the glomerular basement membrane man we could now angiotensin two receptor blockers and ACE inhibitors are very commonly utilized drugs Okay the reason that you also want to think about these drugs is really because because they have the ability to inhibit aldosterone right they reduce aldosterone production what is a potential adverse effect that you may see from both the Angiotensin receptor blockers and the ACE inhibitors so because of inhibits aldosterone you actually can see hyperkalemia so watch out for hyperkalemia because it reduces the glomerular blood pressure it's going to reduce the GFR so if it reduces the GFR it can actually do what to the creatinine it can decrease your creatinine clearance and so the creatinine can actually increase so watch for that as well and the other thing is these are teratogenic so don't give this to a pregnant woman as well so these are some of the things that you want to be able to consider with these particular drugs so Angiotensin receptor blockers they may bump the potassium they may increase the creatinine by dropping the GFR but again I think the other thing is that you get more of a cough a dry cough from the bradykinins and angioedema more particularly from the ACE inhibitors ACE inhibitors can also cause hyperkalemia and drop your GFR and again increase your creatinine so you can see both of these effects and both of these particular drug categories okay but you see more of the angioedema and more of the dry cough in the ACE inhibitors okay the last category my friends is the Angel the aldosterone antagonist and thankfully we've already covered these but just to recap them again aldosterone antagonists is the third category within this drug situation here and this is again your Epler known this is your spironolactone and this is your amyloride and again remember with these that you're inhibiting aldosterone so because you're inhibiting aldosterone you have the ability to cause hyperkalemia so watch out for hyperkalemia and again because spironolactone um blocks the androgens so a lot of steroid hormones that are involved within a lot of you know sex drive and a lot of other things this can potentially lead to one adverse effect that you see called gyneco mastia more particularly with this drug but that is the concept of these ACE inhibitors in these arbs is that they're really really good at being able to treat blood pressure and really reducing your blood pressure through all of these mechanisms that we went through where is the aldosterone antagonist they're really only going to be doing what they're really only going to be reducing sodium and water retention so that may be a benefit if potentially more for the diuretic type of function but you'll see later that this is a drug that has been shown to be potentially beneficial and reduce mortality so it may be a drug that we give to patients who have CHF because it actually can provide some augmentation of diuresis but it also reduces mortality associated with that disease so we'll talk about that a little bit later but that is the whole concept of these drugs now that we've finished these off we have one more category that's our vasodilators let's hop over there all right so now we're going to talk about the last class of drugs which are our vasodilators okay now vasodilating is very interesting right so let's talk about how vasodilation occurs really and what's the overall effect fact if it was in an artery versus if it was like in a systemic vein so if I were to do this let's just do the arterial proportion first here in Red so if an artery right is working to control blood pressure if I have an artery right and it undergoes vasoconstriction right so it squeezes right so it squeezes and when it squeezes it undergoes Vaso constriction what will happen is that will cause an increase in systemic vascular resistance and subsequently an increase in your blood pressure we know that okay the next thing is in the vein the vein is also really important right so when the veins are potentially working and actually being acted on through specific Vaso you know mechanisms vasotone mechanisms when the veins constrict so you have what's called Vino constriction so we're going to call this Vino constriction when they constrict what they do is they help to actually increase preload so they squeeze more blood up into the right heart whereas if I squeeze these arteries I'm making a difficult more resistance to blood flow as it flows through the arterial circuit right so because of that if I increase preload I increase the amount of blood going back to the heart I increase my stroke volume my cardiac output and subsequently I increase my blood pressure so when I give drugs there's two categories of drugs one is called venodilators right so I want to talk about the drugs that are actually what's called Vino dilators and these Vino dilators what will they potentially do these Vino dilators will actually inhibit Vino constriction reduce preload reduce stroke volume reduce cardiac output and reduce blood pressure that's how they'll treat that process and then you have another category of drugs here which are called your arterial dilators and these will work by doing what inhibiting the vasoconstriction of the arteries which will and drop the systemic vascular resistance and drop the blood pressure okay the first category that I want to discuss is the arterial dilators is a really interesting one we're actually going to mention it up here and what these these particular category of drugs is this is actually a drug category which I happen to be very very fond of they are called dihydropyridine calcium channel blockers so dihydropyridine calcium channel blockers really really good powerful drugs now what these do is you obviously can tell via the name that they block calcium channels there is calcium channels that are very mildly present on the venous smooth muscle but way more powerful and way more present on the arterial smooth muscle so these are going to be more particularly arterial vasodilators now what happens is calcium is present on these smooth muscle cells when these calcium channels are open calcium floods in and calcium will actually interact and be utilized within the myofilaments right to be able to allow for contraction so we know that you know calcium binds onto the you know it binds up to the different proteins like the troponin change the shape of the tropomyosin and loss for actin myosin to binding boom you get the sliding filament theory if I give a drug like a dihydropyridine calcium channel blocker what they'll do is they will block the calcium from being able to enter if calcium isn't able to enter is it going to be utilized by the myofilaments to induce contraction no so it will inhibit this process and the smooth muscle will relax if it relaxes it would no longer vasoconstricts it vasodilates if it vasodilates it then this is going to undergo Vaso dilation and if it vasodilates it reduces the systemic vascular resistance if you reduce the systemic vascular resistance you're going to drop the blood pressure what are the drugs that we utilize in this category here there is one particular drug here which I um commonly utilize is called amlodipine amlodipine is very commonly utilized one another one is called nifedipine it's a nifedipine another one is called nicardipine nicardipine another one is called pneumodipine this is a very commonly utilized one or subarachnoid patients and then another one is called clavidipine so with these drugs these are some of the drugs that you can prescribe the most commonly kind of like prescribed outpatient ones are going to be amlodipine and the pedophene and the most commonly utilized one is generally in the ICU or hospital kind of setting or as infusions is clovidipine and a cardiopian very very good powerful drugs now generally with these drugs all right what I really want you to understand is with any arterial vasodilator what is a potential adverse effect that you can see with these drugs great question with an arterial dilator what you do is you reduce systemic vascular resistance you reduce blood pressure what does that do to again your central nervous system it tells the baroreceptors hey hey blood pressure is low so it stimulates the baroreceptors and the baroreceptors once stimulated activates what your central nervous system your central nervous system will then stimulate a increase in heart rate as a reflex tachycardia so watch for reflex tachycardia with arterial vasodilation we saw that with the Alpha One blockers that they can get reflex tachycardia that's a very common adverse effect with these types of dihydroprene custom genome blockers or really any arterial vasodilator because they have very minimal Vino dilation effects they may cause orthostatic hypotension so there is very small and I mean this very importantly it's is a very mild amount of calcium channels that are present on veins very very little so because of that you could potentially see some venodilation effect but it's very very mild and I would focus more particularly on the arterial vasodilation now here's the thing that I want you guys should be asking the question you said dihydropyridine calcium channel blockers like it's something special Zach I don't understand why you mentioned that the calcium channels that are present on the arterial smooth muscle and even on the venous smooth muscle our only dihydropyridine they are only dihydropyridine the other types of calcium channels that are present in other areas like the cardiac myocytes are non-dihydropyridine calcium channel blockers and they deserve a discussion here too we shouldn't just let them out of the discussion as well so let's talk about those drugs so this drug is going to be the second category of drugs here and these are called your non-dihydropyridine calcium channel blockers I'm going to kind of abbreviate nah just we'll write it so non dihydro pyridine calcium channel blockers and these are only present so these are the only ones that are present on the myocardial cells you do not have dihydropyridine calcium channels that are present on the myocardial cells very very important to remember that so these types of structures here the non-dehydripating calcium channel blockers there's two particular agents here one is called Verapamil Verapamil and the other one is called diltiazem deltaism now what's really important with these drugs is that they work on the calcium channels that are on the contractile myocardium and on the nodal cell so on the AV node SC node all those structures and so because of that these have calcium channels that allow for calcium to flood into them right so calcium is supposed to move into the contractile cell stimulate them you know contraction of the contractile cell is also supposed to run into the nodal cell stimulate this cell to generate Action potentials and increase conduction through the heart but when I give a non-dihydropyridine calcium channel blocker what I'm doing is I'm inhibiting these calcium channels I'm inhibiting calcium entry into the contractile cell and into the nodal cell and therefore I will decrease contractility if I decrease contractility of the heart I'm going to decrease the cardiac output and I'm going to subsequently decrease the patient's blood pressure the nodal cell I'm going to reduce the heart rate and therefore I'm going to reduce the cardiac output and I'm going to reduce the blood pressure so these drugs can be utilized and hypertension here's the other thing it's important to remember because these drugs do primarily work on the heart some of the adverse effects that you have to watch out for there's two that are super obvious here one is it can drop the heart rate and so because of that you want to watch out for any types of bradycardia because this can actually drop the patient's heart rate the other thing is it reduces contractility if a patient already has a poor cardiac output such as an decompensated heart failure you could potentially kill them and make them hypotensive put them in a cardiogenic shock so it can really really drop the blood pressure and then put the patient into shock especially if they have decompensated heart failure so avoid in that particular situation one thing that you want to remember is that the non-dehydroputing calcium channel blockers they do have a very mild a very mild vasodilatory effect so these do have a small capacity to bind onto the dihydropyridine calcium channels and inhibit them so because of that I want you to remember that we're going to put this like I don't know let's do it in this beautiful blue color here is that they have an important kind of a mention here is that they have a very small Vaso dilation effect okay and if you're really comparing between these Verapamil has more of a potent effect and deltaizam is a very mild vasodilatory effect so they do have a very small vasodilation effect so therefore they can actually do what reduced systemic vascular resistance and also reduce blood pressure so you may be able to see a small reduction in systemic vascular resistance and subsequently a reduction in blood pressure but it's very very mild whereas these drugs the dihydroperating calcium channel blockers they have no effect on the cardiac myocytes so they have no effect on the cardiac myocytes so they will not be util they won't be able to reduce heart rate and reduce contractility but the non-dehydropening calcium channel blockers they have the ability to reduce heart rate contractility and very mild vasodilatory effect so they will be able to mildly reduce systemic vascular resins if you had to compare which one's better Verapamil has more of a vasodilator effect then diltiazine okay that's the big things that I want to remember for these drugs okay we talked about the calcium channel blockers very very good agents diagram calcium channel blockers happen to be first line one of my preferreds but now let's come down and talk about some other ones with these things we've talked about the calcium channels right how there's very very there's more calcium channels way more calcium channels present on the arterial smooth muscle and very little calcium channels that are present on the venous smooth muscle so calcium still can come in and then again interact with the smooth muscle in these venous cells so if you give a dihydropyridine calcium channel blocker or non-dihydropyridine they have a very mild inhibitory effect so they may cause Vino dilation and what we know about Vino dilation is that Vino dilation does what if you venodilate you reduce preload that reduces stroke volume cardiac output and that reduces blood pressure now that's the basic concept here okay so the other thing is there's there's one more arterial actually two more arterial dilators that I want to talk about they're really really cool to be honest with you so here we have let's say this special enzyme here on the cell membrane this enzyme is called guanol cyclase and what guanolaocyclase does is it takes a molecule called GTP converts it into what's called cyclic GMP and then cyclic GMP act on Exxon an enzyme called protein kinase G and what this does is this actually inhibits muscle contraction okay so generally this pathway would work to inhibit muscle contraction so if I had some way shape or form I could give particular drugs that could activate the guanol outside place that might be able to increase the cyclic GMP increase protein kinase G and inhibit the smooth muscle cells guess what there is particular drugs that can do that all right I can give one particular drug category here one I want to put here and we'll talk about in just a second can stimuli iguana allow cyclase directly and another one does it through another interesting way another drug category can actually do something else where they can increase nitric oxide and when you increase nitric oxide what this does is this also stimulates guanolocyclase if it stimulates guanolocyclase that stimulates this process to increase cyclic GMP that increases the phosphorylation of protein kinase G and that increases the inhibition of the smooth muscles and that will actually cause arterial visibilation reduce the resistance and reduce the blood pressure what are the drugs that actually work too directly stimulate guanolocyclase or increase nitric oxide to activate guanolocyclists let's come down and talk about those so that leads us to the third category here so the third category of drug that I'm going to talk about really interesting type of process here is these drugs are the ones that are going to increase cyclic GMP via stimulating guanol cyclase directly okay so these are actually referred to as what's called direct acting vasodilator so if you really want to put that down here you can actually call these direct acting vasodilators one particular drug within this is called hydralazine okay hydralazine and so hydralazine will work to actually cause again stimulation of guanolocyclists directly increase cyclic GMP increase protein kinaseg and then inhibit the arterial smooth muscle and cause it to relax that'll cause arterial vasodilation that'll cause decrease in resistance and decrease in blood pressure now hydralazine with this particular drug here again we already know that the adverse effect out of this one is already what we've discussed it is going to cause a compensatory reflex tachycardia we should already know that mechanism and have it understood is that it reduces resistance drop blood pressure and creates a compensatory stimulation of baroreceptors to increase heart rate the other thing which is a little odd with this one is that I like honestly it's not completely understood it may cause like an auto antibody production but it actually can cause a drug-induced lupus so watch out for what's called drug induced um SLE here's the one more thing hydralazine does prefer so it does have more of a profound stimulates it's more profound to be able to work and inhibit arteries so when it when we actually compare this it actually will inhibit arteries and cause them to vasodilate way more then it'll actually inhibit veins but nonetheless it does have the ability to inhibit veins very minimally so if you inhibit veins what we'll talk about in a little bit here is another adverse effect from actually inhibiting veins is you reduce preload if you reduce preload you reduce the return of blood to the heart that reduces the stroke volume cardiac output and blood pressure if a patient goes from a supine to seated or a seeded to standing you're trying to fluid shift generally those patients would have an increase in maintenance return if you Vino dilate them they would lose their venous tone they don't have a good venous return and so because of that a potential adverse drug reaction from this as it may cause Ortho stasis another thing about this drug that happens to be safe in pregnancy which is also pretty cool but we'll talk about that a little bit later okay so that's hydralazine the next one is and there's another drug in this category called minoxidil but we don't really commonly utilize that anymore unless you're using some hair like me so you can use that as like Rogaine but the next one here is that we're going to put this in the fourth category here so the fourth category so these are the ones that actually work to increase nitric oxide so they work they work to increase nitric oxide which helps to stimulate guanolocyclase which helps to increase cyclic GMP these are called Nitro dilators now with these Nitro dilators there's actually a couple of them the one that's primarily going to dilate arteries is going to be what's called nitroprocide so there's another drug here called Nitro proside now nitroprocide is an interesting drug okay it does cause intense arterial or vasodilation one of the downsides to this drug I don't ever use it because of this is it can give off a cyanide molecule and this can actually lead to cyanide toxicity so if you think about that imagine why that would be problematic so generally cyanide can actually be taken up by the mitochondria and it will inhibit the electron transport chain so it's going to inhibit the electron transport chain now the electron transport chain isn't going to be able to take oxygen utilize that and then make ATP this is inhibited now and so because of that what does your body shift into utilizing as an energy source it starts you know undergoing anaerobic glycolysis and so because of that what happens is the result of the cyanide toxicity is that the patients May develop what's called an increase in lactic acid so they can have what's called lactic acidosis as a potential adverse effect so you can see cyanide toxicity with high doses you can see lactic acidosis with high doses a secondary of the cyanide toxicity there's one more thing cyanide is not the only problem here it's also been shown that this drug if you take the coronary vessels here so here's going to be the coronary vessels here's a coronary vessel and it's splitting and I'm going to have one going here and I'm going to have another coronary vessel kind of going this way okay let's say here there's a plaque in this part of the vessel okay and there's no plaque in this part of the vessel what nitroprocide will do is it'll actually kind of like vasodilate the healthy coronary vessels a little bit too much if I vasodilate this healthy coronary vessel in comparison to this placked up vessel look at the difference now so I'm going to kind of dilate this one up I'm going to exaggerate it a little bit now I'm going to dilate this puppy now this vessel is under much lower pressure this vessel is under much higher pressure where is the blood going to want to go it's not going to want to go down this coronary vessel that's for sure it's going to want to all go down this coronary vessel and so because of this this is actually somewhat dangerous and can actually lead to the myocardial cells so imagine here's a myocardial cell and then here's a myocardial cell what's going to happen to this poor myocardial cell that's getting almost no blood flow they can start to become ischemic and potentially die this is called coronary steel syndrome so you want to watch out for this too as a potential complication called coronary Steel syndrome this is another potential adverse effect of this drug and why I'm not a huge fan of this drug okay there is another one I'm going to briefly discuss it here because it actually does two things so I'm going to end up mentioning it twice so the next one here is called nitroglycerin now nitroglycerin what I want to do is I'm just going to write one particular thing here nitroglycerin does have the ability again to do everything that nitropresside does right so increased nitric oxide activate guanol cyclase increase cyclic GMP cause vasodilation Okay particularly the arteries but in order for it to be able to cause arterial vasodilation it has to be at extremely high doses so it's important to remember that nitroglycerin actually prefers to inhibit veins so to cause Vino dilation way more so than it prefers to cause inhibition of the arteries so arterial vasodilation the only reason it would actually start to inhibit the arteries and actually cause arterial vasodilation this is actually important so I'm going to write it here in this blue here is that it only will actually do this particular process here when you're at extremely high doses of nitroglycerin so at extremely high doses of nitroglycerin then you will start to get more arterial vasodilation and so that's why nitroglycerin technically can't be in arterial vasodilator but it has to be an extremely high doses like upwards of like 300 400 mics of nitroglycerin to be able to really get a vasodilatory effect of the arteries okay so so far with arterial vasodilators we have covered the non-dihydropyridine which is very mild for aptamil detizing they're mainly inhibiting heart rate inhibiting cardiac contractility we talked about dihydroperating very powerful vasodilators amlodipine nifedipine nicartipine pneumodipine clovideopene we talked about those then we talked about the ones that directly act on the vessel to increase cyclic GMP hydralazine minoxidil and then we talked about the ones that increase nitric oxide which activate guanocyclase and increase cyclic GMP and all of these things help to relax the vessel that would be nitroprosite and that high doses you can dilute the arteries with nitroglycerin all right so we talked about the arterial dilators right we talked about them pretty in depth we talked about the non-dihydropriating the dihydropyridine we talked about hydralazine and we talked about Nitro peroxide nitroglycerin the venodilators are not really that many and they're not really super powerful at treating hypertension to be honest with you but we're going to briefly mention them for the sake of the you know completeness of the lecture but when we talk about Vino dilators one of the concepts here is that whenever you kind of work to dilate the veins we've already kind of mentioned that calcium channel blockers have a very mild effect on the veins in dilating them but there is this same mechanism over here on the veins much more powerful with respect to this so because of that there is this enzyme here called guanol cyclase and again guadalocyclase when it's activated can take and turn what's called GTP into cyclic GMP that can work to act on protein kinase G and protein kinase G will work too inhibit this particular smooth muscle from Contracting now if I give a drug that works to increase nitric oxide that will stimulate the guanolocyclase increase the conversion of GTP into cyclic GMP increase protein kinase G activation and inhibit the smooth smooth muscle cell from Contracting so because of that really it's this kind of concept yes hydralazine may be able to directly activate the guanolocyclase and the veins but again I want you to think about it more as an arterial vasodilator very minimal venous dilation the primary thing here is we're left with the Nitro dilators and we've already talked about nitroglycerin and we said that's a primary venodilator the other one that we're going to talk about is called an isosorbide dinitrate let's talk about those so for the venodilators they're not super powerful antihypertensives but we already talked about the Nitro dilators for the arterial system nitropresside and then nitroglycerin at high doses the venodilators will put this as the fifth category this is another Nitro dilator so it's the same concept here they work to increase nitric oxide they help to stimulate guanol cyclase they help to increase cyclic GMP and again how what kind of category are they in these are Nitro dilators we talked about the Nitro dilators in the arterial system which is going to be pretty much what nitropresside and high-dose nitroglycerin for the venous dilation this is low dose nitroglycerin low-dose nitroglycerin because at low doses it prefers to Vino dilate than it does arterial dilate so that's an important thing to remember here now with any type of Vino dilation we've already talked about this but when you xenodilate you reduce preload you reduce stroke volume critic output blood pressure and especially if the patient goes from a seated to a standing a supine to a seated there's fluid shifts you reduce their venous return so one of the adverse effects out of this particular drug category with any Vino dilator is what you may experience what type of effect here orthostasis so this may be very common with these but there's one more thing with nitroglycerin very important especially for your exams because nitroglycerin really Vino dilates you better be careful with a patient who has an RV that can't take a joke if their right ventricles are just jacked up and it's not able to contract and it's not squeezing blood out of the right ventricle into the left heart so now if you have a patient who has what's called a right ventricular myocardial infarction why is that a problem this RV can't take a joke so it already is going to be reducing the amount of blood going from the right ventricle to the left ventricle so there's a left a decrease in the left ventricular preload because it's not going to be able to push as much blood to the left ventricle right because it's jacked up if that's the case the left ventricular cardiac output is going to drop and then the left ventricular blood pressure is going to drop your systemic blood pressure is going to drop right now give them a nitroglycerin what are you going to do if you give this patient nitroglycerin guess what you're going to do on top of the RV already being all jacked up you're going to decrease the right heart venous return that's going to decrease the left ventricular preload even more that's going to decrease their left ventricular cardiac output decrease the left ventricular blood pressure and you're going to kill them because you're going to put them into a hypotensive state so when a patient has a right ventricular Mi that can't take a joke you better be very careful because it can really really drop this patient's blood pressure so that's one thing avoid Nitros in patients who have uh who have a right ventricular mind the other one is avoid this medication in a patient who has what else who's taking a drug that acts similarly like a phosphodiesterase inhibitor or an alpha blocker so avoid this and a patient who's taking what's called a phosphodiesterase five Inhibitors are out there on that Viagra for the and then another one is an alpha blocker okay so an alpha blocker would also do this they can also block the veins if you do that you're reducing venous return extra so for this one you're going to significantly drop the preload they're going to significantly drop the stroke volume cardiac output and they're going to drop the patient's blood pressure so watch out because again hypotension may be an overt effect from combining nitro with a phosphodastrace inhibitor or an alpha blocker the last one here is a part of these Vino dilators and this is called isosorbide dinitrate really this drug is only commonly utilized and we'll talk about a little bit later it's a very potent venodilator so because it's a potent venodilator it's really good in situations the only true indication that we would utilize this for is in patients who have heart failure so have heart failure and are African-American and they're already taking and they're on hydralazine hydralazine and because this has been studied it's actually been shown to potentially be beneficial maybe even reduce mortality mildly and patients who have African-American descent have heart failure and already on hydralazine you may be able to add isosorbide dinitrate to reduce the preload reduce the congestion in patients who have heart failure all right my goodness we talked about all the vasodilators here and again I think the big thing to think about is if it's an arterial vasodilator what's the most common adverse effect reflex tachycardia or obviously hypotension with Vino dilators what's the most common adverse effect orthostatic hypotension because you're reducing preload so don't forget that all right now let's go into particular anti-hypertensive medications and who we would prescribe this to especially if they have an underlying comorbidity all right my friend so we have covered every drug category that is an anti-hypertensive agent we talked about some patholytics we talked about diuretics we talked about patients who we talked about Renaissance and aldosterone synthesis Inhibitors and we talked about vasodilators we went over all the different types of drugs we went over particularly how they work we went over some of the adverse effects we covered some indications of some of them along the way but what I really want you to understand is now that we know of all of these drugs we know their names they know how they work which is like really important and some of their adverse effects we should really now be able to understand what type of situations I could actually give this hypertensive agent to a person who maybe has an underlying comorbidity so generally there's an easy way if I have a patient who has no problems no diseases and we'll talk about that a little bit later that's the easy ones to tell them oh prescribe this one prescribe this into anti-hypertensive prescribe this anti-hypertensive it's more challenging to prescribe an anti-pretensive when a patient has other comorbidities such as the ones that we're going to list here and what I want you to understand is not just to memorize don't just memorize all you can give this drug or medicine no no why you give this drug in this particular situation so you can remember it okay and then after we go over giving hypertensive agents to people with underlying comorbidities which one's best and then we'll cover the easy one which is patient doesn't really have any other underlying comorbidities what are the best agents for them what are the first line anti-pretensives and then what we'll do is we'll talk about a patient who comes in they got a stroke their heart's about to explode they Gotta Die an aortic dissection they're peeing blood and nothing but a hypertensive emergency because their BP is one over 185 over 126. and those situations what are the best agents to give we'll talk about that at a hypertensive emergency but first things first we have a patient here who has atrial fibrillation they have atrial flutter maybe they have like a super ventricular tachycardia that's chronic for them and they have hypertension which one about all the agents would be best for these patients and think about it if a patient is atrial fibrillation atrial um flutter SVT in some way shape or form their nodal cells are hyperactive and they're firing and so in these particular patients they're having increasing heart rates right which is going to be doing what increasing their cardiac output increasing their blood pressure potentially okay well then you got to go back and think on the nodal cells there were two types of things that I can modulate one was a beta 1 receptor so one of these was a beta-1 receptor actually a student read because it was red and looked cool so this was a beta 1 receptor and the other one was a non I'm going to kind of put them in a breed as non-dihydropyridine calcium channel oh okay well if I give a drug like a beta blocker and I give a drug like a non-dihydroputing calcium channel blocker what I'll do is is I'll inhibit this beta receptor from being stimulated which will try to increase the heart rate so I'll inhibit this process and I'll reduce the heart rate I'll reduce the cardiac output and I'll reduce the blood pressure and at the same time these patients hearts are beating really fast I'll treat their afib their a flutter and SVT because the problem with these patients is they have fast heart rates well if I give a drug like a beta blocker that'll do that if I give a drug like a non-dihydropyridine calcium channel blocker inhibit the calcium from entering into this nodal cell then calcium will not come in if calcium doesn't come in as I inhibit this process it's not going to be able to do what stimulate Action potentials in the nodal cells down the AV node or down the SC node AV no bundle of His bundle branches per kg system because of that it will drop the patient's heart rate drop their cardiac output and drop their blood pressure so because of that these would be two great drugs and patients who had hypertension Plus have some tachyarrhythmias so what are these two particular drug categories this would be one would be a beta blocker a beta one blocker so this would be things like metoprolol asthma law Atenolol bisoprolol things of that nature and then the second one would be what a non-dihydropyridine calcium channel blocker like varapamil like diltiazam that makes sense right so that's what I want you guys to be thinking about in this particular situation all right so patient has hypertension and they have attacker arrhythmia give them something that drops their heart rate pretty straightforward the next one is coronary artery disease and angina so a patient has some type of disease process where their myocardium right here's our myocardial cells here so here's the myocardial cell so these are the myocardial cells and this is a coronary blood vessel and blood is supposed to be moving through this coronary blood vessel nice and easily and giving off oxygen to these myocardial cells so that they can use it to generate contractions to generate Action potentials all of those things we need it the myocardial cells needed but if they have a big old stinking plaque here that's really altering the decreased blood flow so now there's decreased cerebral blood I mean so there's decreased coronary blood flow and there's decreased exchange of oxygen across this big fat plaque into the myocardial cells that's going to reduce the oxygen delivery to the myocardial cells if you reduce the oxygen delivery to the myocardial cells that can lead to ischemia now imagine that a patient also has another problem so here's what happens to coronary artery disease and one particular situation here we reduce oxygen supply because of the plaque right now here's the other problem a patient who has like unstable angina or an nstemi it's not completely occluded it can be partially occluded but now here's where it gets really really problematic if the patient's myocardial cells need more oxygen because the patient's working harder for whatever reason like they're hypertensive if they're hypertensive now their myocardium has to work harder to pump blood out of the heart and so because of that with that situation what you can get is in a decreased oxygen supply you can have The myocardium have an increase in O2 demand and this is a recipe for disaster when The myocardium is requiring more oxygen you don't have enough oxygen to be able to give to it what's the ultimate result here ischemia to the heart and so the ultimate result here is this is going to lead to ischemia and if not treated there's an increased risk of infarct to The myocardium so I can't change the oxygen supply in these patients that's where I'd have to go in and rip the you know stent open the vessel or cut the plaque out I can't do that with drugs but I can give a drug that reduces the O2 demand in other words the heart doesn't have to work as hard to pump blood out of it well how do I do that well let's let's take a second here to look here well one way one way is if I work to inhibit those nodal cells so one way is I can take the nodal cells if I block the beta receptors and I block the calcium channels that allow for flow into them right so here I'm going to block these channels here I'm going to block these calcium channels now calcium can't come in right so there's not going to be able to be calcium here and then I'm also going to block the beta 1 receptor so now they can't stimulate the nodal cells so what's the overall effect if I inhibit the nodal cells I can decrease heart rate that will decrease cardiac output that'll decrease the work of the heart right so I'll decrease the demand so effectively what this will do is this will decrease the demand of the heart all right that's pretty good if I can reduce the demand that may be helpful because then I'm not going to require as much oxygen so I could give drugs that potentially can reduce the heart rate by inhibiting the non-dehydripating calcium channels right so I got to inhibit these and I have to inhibit the beta 1 receptors so that's already these drugs that I just talked about they'll be able to do that but you know what else is another benefit of them if we look at the other cells look at the other cells here not just the nodal cells but also the contractile cells so here's my contractile cell so this was a nodal this way I'm just going to put nodal cell this is a nodal cell here is a contractile cell and again on this I have beta 1 receptors and what else do I have on it non-dihydropyridine calcium channels so if I give a drug that'll block calcium entry into this contractile cell and I give a drug that'll block the beta 1 stimulation that'll reduce what well think about it if I give drugs that inhibit the non-dihydro dihydropriating calcium channels and I give a drug that blocks the beta-1 receptors what am I going to do I'm going to decrease contractility so if I decrease contractility I'm going to decrease cardiac output decrease work and decrease demand so all I got to do to really cause the heart to not beat as fast and to not contract as hard which means it's not going to use as much oxygen which means it's not going to have as high of a demand that would help in coronary artery disease and angina so any basically any patient who has unstable angina nstemi or maybe even stable angina where they're working really hard this would be a particular drug that I could utilize so what are these one is a beta blocker two is a calcium channel blocker okay particularly non-dahydropyridine they're not super powerful but they can be somewhat beneficial the next one all right this one's really cool we have two mechanisms for this one there's another drug which helps to be able to Vino dilate okay so this drug will actually work too vinodilate so it'll take this venous smooth muscle cell so here's my Venus smooth muscle cell here's my venous smooth muscle cell right here so Venus smooth muscle cell and what I'm going to do is I'm going to give this drug and this drug is going to increase nitric oxide inside here so it's going to increase nitric oxide it's going to activate what type of enzyme guanol cyclase that's going to take GTP convert it into cyclic GMP and that's going to act on protein kinase G and protein kinase G is going to inhibit muscle contraction so your effect here is you're going to inhibit muscle contraction this drug is a really powerful Vino dilator called nitroglycerin called nitroglycerin and what nitroglycerin will do is it'll increase nitric oxide stimulate cyclase increase cyclic GMP increase protein kinase G and inhibit the actual venous smooth muscle cell from Contracting if that happens and I inhibit this smooth muscle cells in the veins from Contracting I reduce the preload to the right heart if I reduce preload to the right heart what do I do to the stroke volume the cardiac output the amount of work that the heart has to do to pump out more blood so generally if you have a lot of preload if you have a lot of preload that means that you're going to higher stroke volume your heart's going to have to work harder to pump all that volume of blood out if I reduce the preload I reduce the volume of blood going to the heart that it's going to have to work to pump out that decreases the work it has to do it decreases demand so by dilating the veins what do I do my friends dilating the veins I'm going to inhibit the Venus with muscle cells I'm going to Vino dilate if I venodilate what do I do I reduce preload if I reduce preload I reduce stroke volume and cardiac output the amount of work that the heart has to do to pump that blood out of the heart there's less volume coming into it less work that it's going to have to do if there's less work there's less demand that's a pretty cool concept there so that's one that's one indication so here's one indication there the second thing is that the nitroglycerin not only can act as a Veno dilator but it can octo also act as a coronary vasodilator so here's the coronary vessel here very little blood flow getting through now what I'm going to do is I'm going to give this patient nitroglycerin and what it's going to do is it's going to cause coronary vasodilation and if I cause coronary vasodilation I'm going to increase the actual blood flow to The myocardium and so that'll increase maybe a little bit of the oxygen supply to The myocardium so that was the only one that I may be able to get just a little bit more Supply to The myocardium and reduce the work that's a great drug again what is this drug that'll do these two things here this is Nitro glycerin so I want you to understand in patients who have some type of coronary artery disease or angina whether it be unstable engine a stable angina and stemi they may benefit preferably generally if I had to pick between a beta block and a calcium channel blocker the beta blocker should always be first the calcium channel blocker should be second and if a patient develops symptomatic angina so unstable angina or they develop and stemi they have chest pain nitroglycerin may be very helpful for symptomatic control to again xenodilate reduce oxygen demand and give a little bit of coronary vasodilation so to open up the actual coronary vessel to give more blood flow to The myocardium okay so that's the particular indications for this situation okay a lot of stuff there okay the next indications that I want to talk about here besides a patient who's tachycardic a patient who has stable plaques within their vessels or maybe an unstable plaque that ruptured and again they have a reduced Supply and we try to reduce their demand the next situation here is a patient just had a myocardial infarction so they just you know jacked up a piece of their myocardium or they have heart failure so systolic heart failure where their heart isn't pumping in general so the basic problem with this disease is what the basic problem is is that the heart is not pumping out very well there is a decrease cardiac output that's being generated by the left ventricle it's not very good the contractility is down so because of that it's having difficulty being able to get blood out of the left ventricle and into the aortic circulation and into the systemic circulation right so there is a reduction in cardiac output the problem with that is whenever you have a reduction in cardiac output because patients are post Admire have heart failure systolic heart failure is it loves to activate those Barrel receptors my friends and they pick up from the you know carotid um the carotid sinus and aortic sinus and they send this information to your central nervous system from your central nervous system you activate your sympathetic nervous system that increases the release of norepinephrine and what we know is that norepinephrine will then go and do what it'll act on the heart on the beta receptors and it'll act on the blood vessels to do what a lot of problematic things here so one of the things that it's going to do is it's going to act on the heart and it's going to try to do one nasty thing here so if we increase norepinephrine let's actually say if it works on norepinephrine so we increase norepinephrine release if it increases norepinephrine release what's it going to do to the beta 1 receptors so on the beta 1 receptors it's going to stimulate them and do what increase heart rate and increase contractility this poor heart is already weak you're going to weaken it even more okay you're going to weaken it even more by doing that so by doing this by stimulating the beta 1 receptors you're going to weaken the heart even more that's terrible so I'm I'm what am I doing by increasing my heart rate I'm doing what heart rate and contractility I'm doing what to the heart I'm weakening it well that's a problematic thing well here's the other thing not only is norepinephrine going to increase the activation of the beta 1 receptors it's also going to stimulate the alpha-1 receptors what's that going to do that's going to cause increased systemic vascular resistance and it's going to increase preload so now if I increase the stomach vascular resistance I'm going to squeeze down on these arteries and I'm going to make it harder for blood to even get out of the heart because I'm going to increase afterload oh my gosh so if I increase my systemic vascular resistance I increase afterload that weakens the heart even more makes it even more difficult to get blood out of the heart poor thing now I also am going to increase preload so I'm going to give it more blood so I'm going to fill it up I'm going to congest it and I'm going to have it more blood unfortunately and weaken it even more so you see how this is problematic right so what I can do is I can give drugs that block the beta 1 receptors that block The alpha-1 receptors and patients who are posting my nchf what are the drugs that actually can block beta 1 receptors that would be one particular thing but if I also had drugs that block the beta and Alpha oh I do have drugs that do that so one category would be selective selective beta one blockers so beta one blockers that would be your Atenolol bursoprolol metoprolol esmolol Etc the other one is your Alpha and beta blockers labetalol Carvedilol Carvedilol more particularly is really really good at this so I'd actually remember that with Carvedilol actually being way more powerful than labetalol especially in patients who are post Mi and CHF but you're going to get way more potent effect here from The Selective beta 1 blockers so metoprolol tends to be one of the most commonly utilized ones and patients who are post Mi or CHF because again you're reducing heart rate contractility that's one of the big things that'll really weak in the heart but again if you have a drug that actually has the ability to reduce Alpha One blockade you can reduce afterload which helps to again get more blood out of the heart and reduce preload which helps to prevent as much blood coming back to the heart congesting it even more which is beneficial so Carvedilol tends to be way better than labetalol in that situation okay so that's that now here's that's not the only problem though the norepinephrine not only does it increase the stimulation of beta 1 receptors Alpha One receptors but it also stimulates one more that stimulates beta 1 receptors that are present on the kidney and that will actually increase renin Angiotensin aldosterone ADH system and that can also be somewhat problematic plus if you have a reduction in cardiac output that also stimulates the red and angiotensinaldosterone system and so they may have potential benefits so if I stimulate the random angiotensinaldoctrine system because I have a low cardiac output low blood pressure activate the bare receptors and they stimulate that reflex that's one way plus if I have a low cardiac output I actually don't perfuse the kidneys well the JG cells get ticked off and release renin and that activates the system so won't those drugs also be good yes let's talk about how they do that come down here with me for a second all right so again we've talked about how beta blockers will work potentially in the post Mi CHF they'll inhibit the beta 1 receptors which will inhibit the increase in heart rate inhibit the increase in contractility which will again prevent the weakening of the heart that's actually really good because I can reduce mortality within this disease and then if you have drugs that actually inhibit The alpha-1 receptors they can reduce the systemic vascular resistance reduce the preload and again reduce the ability ability to continue to weaken the Heart by causing it to undergo dilation or hypertrophy all of that and then I also May inhibit the activation of the renin angiotensinal aldosterone system so beta blockers more particularly inhibits the beta 1 receptors and then alpha blockers and beta blockers like label Carvedilol particularly Carvedilol will inhibit both of these processes which is pretty cool now coming back to this situation here patient sympathetic nervous system is activated when the sympathetic nervous system is activated because again if you knock out this left ventricle where because you had an MI you have very poor you know cardiac output because there's a you know decrease in systolic function here right so the whole point here is there's a reduction in cardiac output the other thing here is that if there was a reduction in cardiac output and a reduction in blood pressure that'll activate those you know carotid sinuses aortic sinuses which will go to your medulla medulla will then activate the sympathetic nervous system and this will come down to the kidneys and activate the what types of receptors here they'll activate the beta one receptors on the JG cells of the kidney the other thing is that if you have a low cardiac output that'll activate the JG cells in the kidney if you activate the JG cells in the kidney they then will release renin renin then converts this molecule made by the liver which is called angio tensinogen into Angiotensin one Angiotensin one is then acted on by an enzyme in the lungs called Angiotensin converting enzyme which we'll convert this into Angiotensin II Angiotensin II then has many different effects which we've already discussed right one of them is that it can go over here to the arteries and act on Angiotensin II receptors and do what it can stimulate them which can increase systemic vascular resistance increase your blood pressure and because of that not only does it increase resistance it also increases afterload the other thing here is that Angiotensin II can also act on the veins on the Angiotensin II receptors here and that can do what that can increase the preload increase the stroke volume cardiac output and increase the blood pressure and again the whole point here is that if we increase preload we're actually going to push more blood into the heart right if we push poor blood into the heart it's going to get congested so one of the things that we're already noticing here with an increase in Angiotensin II which is the problematic guy here is that when you increase angio tens in two is you're going to increase systemic vascular resistance and that's going to increase after load that's going to put a lot of strain on the heart that's going to weaken it it's also going to increase preload which is going to again increase the what it's going to increase the strain of the heart and it's also going to cause it to become congested so if you cause it to become congested because of an increase in preload and then you because of the high afterload you cause to become very weak over time the other thing here is that Angiotensin II also acts where on the adrenal cortex to pump out more aldosterone and then aldosterone does what acts on the kidneys and what it does is it actually is supposed to stimulate sodium and water reabsorption and so what it'll do is it'll actually cause more sodium and more water to go into the bloodstream and so then you'll have an increase in blood volume and increase in preload and it's the same concept here so it'll actually stimulate aldosterone which will do the same thing so aldosterone will also so we'll just put here aldosterone is also going to be increased but that just stimulates this increase in preload and causes the heart to become more congested so this is a problem this is a this is a really terrible situation here because in a patient who has a post Mi or CHF by doing all of these things what are you doing you're weakening that poor heart so what about what if I gave two particular drugs or three drugs one drug category is an Ace inhibitor what that'll do is that'll actually reduce Angiotensin II less Angiotensin 2 means less vasoconstriction of the arteries in the veins that reduces afterload that reduces The Strain on the heart and prevents it from getting weak reduces the preload reduces the stroke volume and the cardiac output reduces the congestion of the heart which helps to play a world within reducing CHF sickness and then it also inhibits aldosterone production which reduces further preload the same thing if I gave a drug that blocked Angiotensin II from binding onto all of these receptors I would get the same effect so ACE inhibitors and arbs would have what potential benefit here they're really good in patients who have CHF and post and post Mi because they would both of them reduce preload and they would also reduce afterload which helps to prevent weakening of the heart there's one more and this is more particularly for the CHF picture but you can't think about in post Mi as well and that's aldosterone antagonists if you give an aldosterone antagonist like what like the Epler known or the amaluride these may be beneficial to be able to do what reduce preload and again reduce that Progressive congestion of the heart and what's really interesting is that all of these drugs the beta blockers alpha beta blockers ACE inhibitors arbs and aldosterone antagonists have all been shown to be able to reduce mortality in patients who have CHF and in some degree post MI so these are the ones that I want you guys to be thinking about so so far we've covered patients who have tachycardias or tachyarthemias we've covered patients who have maybe a stable plaque or an unstable plaque and they have a high oxygen demand and a decreased O2 Supply how do you reduce their demand and then we talked about patients who just had a myocardial infarction recently maybe a couple months afterwards or they have systolic heart failure and they're not having good cardiac output and their hearts getting weaker and weaker and weaker how can we prevent that if they also have Associated hypertension man I think we're understanding this now okay so we got those beta blockers calcium channel blockers non-dihydroperating here beta blockers not dihydropening calcium channel blockers nitroglycerin here beta blockers alpha beta blockers we also have ACE inhibitors arbs and aldosterone antagonists for this one what about diabetes and CKD okay and patients who have diabetes really the underlying problem here is that in diabetes they have maybe like less insulin or they have maybe they have high insulin whatever the problem is there's either type 1 which is the no insulin being produced or zero insulin or type two they have lots of insulin it's causing resistance but the problem here is that regardless of these two diseases they're increasing the blood glucose levels the problem with that is that has a really terrible effect on the kidneys and can actually progress this patient into chronic kidney disease so diabetic nephropathy is one of the very common causes of chronic kidney disease if a patient also has chronic kidney disease of an undetermined etiology another maybe it's hypertension related either way diabetes can lead to CKD or if they have CKD from another underlying cause like hypertension there is particular drug categories that are beneficial here now let me explain and a patient who has some type of hypertension but they also have these two diseases it's really interesting okay in diabetes or CKD they have poor kidneys poor renal perfusion in general so because of that these patients may have a lot of renin production lots of renin leads to an increase in Angiotensin one we're not going to go through this mechanism and crazy but increases angiotensin two and then Angiotensin II will do what here is your afferent arterial blood's going into the glomerulus and then here is the efferent arterial blood is leaving the glomerulus here and then exiting out this way Angiotensin II has a very very powerful effect on the efferent arterial what does it normally do the normal effect of Angiotensin II here is to cause efferent arterial Vaso constriction right it stimulates that process that increases the glomerular blood pressure so the pressure inside of this glomerulus here is now going to be very very high because I'm squeezing down here so I'm reducing blood exiting here so less blood is going to be coming out of the glomerulus and more of it's going to be staying in the glomerulus that's going to increase the glomerular blood pressure that'll increase the glomerular filtration rate that'll increase protein loss and that will also thicken the glomerular basement membrane from consistent stress because it's going to have to thicken because it's under high pressure it has to protect itself so you're going to see all of this particular process here where there's lots of protein lots of loss of potential fluids here right so you're going to see potential protein urea and an increase in the GFR and you're also going to see look at this glomerular basement membrane it's all jacked up it's all thickened up now and that's going to worsen and progress in the chronic kidney disease so thickening the glomerular base membrane will worsen the chronic kidney disease so it'll increase the CKD so now we have a special enzyme that converts Angiotensin 1 into Angiotensin II this is called Ace we have a potential receptor here called an angiotensin two receptor where Angiotensin II binds onto um if I give a drug such as a what Ace inhibitor oh man we good ace inhibitor such as lisinopril captoprolanylopril right is going to inhibit this enzyme it's going to inhibit Angiotensin 1 and Angiotensin II it's going to decrease or inhibit the levels of Angiotensin II if I give an Angiotensin II receptor blocker it's going to inhibit the Angiotensin II from binding onto the receptor what is the overall summative effect of these things then oh man if now we block this effect here we're going to have less Angiotensin too so less Angiotensin II is going to be occurring whether it be less Angiotensin 2 being formed or it's less Angiotensin tube binding to the receptor so it's this or Angiotensin II blockade if it's blocked that inhibits efferent arterial Vaso constriction now it's not going to vasoconstrict it's going to dilate more blood flow leaves what does it do to the glomerular blood pressure it reduces the glomerular blood pressure what does that do to the GFR it increases the GFR I'm sorry it decreases because now your pressure in the capillary system is going to be lower so you're going to have less filtration the hydrostatic pressure will go down it also will decrease protein loss less proteins are going to be lost in the urine so you're going to inhibit protein area which is great in diabetic nephropathy and chronic kidney disease and then also you're going to decrease GBM thickening and this is great because why because this will decrease progression of CKD so this will decrease the progression of CKD oh my gosh these are great drugs to use in that situation then so this is what I want you to think about when you think about patients who have diabetes and CKD why ACE inhibitors and why arbs are going to be the preferred drug to give in these patients okay let's move on to a couple more diseases and which ones we would use for if they have another comorbidity all right guys almost done just a couple more types of anti-pretensive agents that we would use in patients with underlying comorbidities so first one BPH so you're probably like BPH what does this happening I thought we were going to go with the more realistic ones like tachythmias or patients who have Cad and agile or have some type of post in my heart failure or diabetics and CKD yes yes but BPH is important too when you can't pee that's problematic so when you've got a big old honking you know prostate that's actually preventing you from being able to go to the bathroom and being able to pee so it's causing retention sometimes what we can do is alpha blockers right alpha blockers have actually been shown to be really beneficial at being able to treat the patient's blood pressure as well as being able to inhibit the internal urethral sphincter so if you inhibit the internal urethral sphincter this helps to be able to promote urination which is a very beneficial thing in a patient who has retention secondary to BPH so that might be a benefit in this particular category such as Alpha blocker so prazasan terrazasin doxazos and tamsulosin et cetera osteoporosis what the heck and osteoporosis sometimes the problem is that they're breaking down lots and lots of bone very very porous bone and because of that you're actually breaking down tons of bone that you may not have enough calcium to put back into the bone and patients who are taking what's called thiazide diuretics so thiazides what thiazides do is yes they inhibit sodium and water retention yes that is absolutely the case and so that'll drop your blood volume and then through the mechanisms we talked about before drop your blood pressure but here's the thing that it also does it also stimulates calcium reabsorption and if you increase calcium in the bloodstream you can use this calcium to deposit into the bone in patients who have osteoporosis so thiazides are also beneficial in patients who have hypertension but they also have osteoporosis because one of the adverse effects can actually be a benefit which is hypercalcemia all right the next one pregnancy patient is pregnant there is many different drugs that you really want to avoid and so instead of remembering the ones that you want to avoid just remember the ones that you really are safe have a good safety profile and you'd want to give those particular drugs that you want to give let's actually write these down a nice red so we remember them is healthy moms love nifedipine so the first one is obviously nifedipine so this is that dihydropyridine calcium channel blocker so that's a pretty safe drug the other one is labetalol which is an alpha beta blocker the other one is methyl dopa but you probably like methyl dopa don't worry throw the alpha in front of it and then the last one here is hydralazine so these happen to be very very safe in patients who are pregnant so consider these on the exams if they present that all right with COPD and Asthma the basic concept here is that you really want to reduce the bronchospasm you want to reduce a lot of the coughing that comes from that disease so you have to think here I have different types of receptors here right one is I have beta 2 receptors the other thing is that there's a lot of capillaries that are controlling the blood supply to the submucosa here and so I really don't want a lot of like leaky vessels so I think the biggest thing to think about is really which drugs to not give to patients who have COPD asthma because the the list is a little bit shorter and then you can remember anything else would be safe so the drugs that you should not give to patients with COPD and Asthma is you don't want to give drugs that block the beta 2 receptors if you give a drug that inhibits the beta 2 receptors what are you going to do this is going to promote it's going to stimulate Broncho spasm because you're generally beta2 receptors when they're stimulated they actually promote bronchodilation if you inhibit that it can cause bronchospasm and that can worsen the COPD and Asthma on top of that there's a particular situations here where when you give a patient what's called an Ace inhibitor an Ace inhibitor is actually important because what it's going to do is it's going to inhibit an enzyme called Ace and Ace will take a molecule called bradykinin's and convert it into these inactive metabolites and if you give an Ace inhibitor you inhibit the ace enzyme inhibit bradykinus from being broken down and increase bradykinin's and bradykinins actually promote a lot of vasodilation and capillary permeability in the increased cap permeability and that causes swelling angioedema and coughing so avoid the drugs to avoid is ACE inhibitors and beta blockers let's actually put these over here the beta blockers any other drug may actually be potentially beneficial or safe to give to patients who have COPD asthma so avoid beta blockers more specifically than non-selective solubetalol Carvedilol Propranolol not as much so metoprolol asthma law and Atenolol is butylabisoprolol minor minor effect of bronchospasm but primarily labetalol Carvedilol propenolol avoid those and then avoid ACE inhibitors arbs they have a very mild very very very very low chance of angioedema but again very very mild very very low chance so again arbs would be safe um any kind of like dihydropyridine calcium channel blocker will be safe hydralazine any of those drugs that we've talked about before besides these would be potentially safe to give in a patient with COPD or asthma just avoid ACE inhibitors and avoid beta blockers all right so that covers all of the patients who have hypertension with an Associated comorbidity such as we've covered in this lecture we covered um tachythmias we covered uh angina where there would be unstable whether it be stable whether it be end stemi we covered post in my congestive heart failure we covered um potentially patients who have diabetic diabetes or CKD we cover BPH osteoporosis pregnancy and we finished off with which ones to avoid in COPD asthma now let's talk about the patient population that is uncomplicated they don't have any of these particular diseases relatively healthy but they have essential hypertension which are the best anti-hypertensives for these patients to know let's talk about that all right so the first one that I want you to think about is three categories so a patient who is not old all right is non-african-american has a has high hypertension those who are not elderly are African-American have hypertension and those who are elderly with hypertension okay regardless if they're African-American non-african-american the reason why is this has been studied okay and there's been shown to be potential benefit within particular agents in essential hypertension in these three categories so if they're non-elderly non-african-american they may benefit from potential first-line medications such as ACE inhibitors or arbs and then another thing that you could combine with that so I could do an Ace inhibitor or an ARB really is one of the options here and then the last thing I would also consider here if you had to do combination therapy so generally with a patient that may start off with an Ace inhibitor or an ARB and then after I start these off if the patient is still not reaching their goal which maybe I'm targeting a goal blood pressure less than 140 over 90 but they're not meeting it with an a snippet or an ARB I would obviously increase the dosage but if they're still not meeting it then what I would do is I add on another drug and the drugs that seem to be beneficial in these patients are thiazide diuretics so thiazides so chlorthalidone chlorothiazides these tend to be very very beneficial in these patients okay so again non-elderly non-african-american with hypertension ACE inhibitors or it's important to remember that you don't want to get both of these or arbs for and then another thing that you can add on here plus or minus plus minus thiazide diuretics okay so like Hydrochlorothiazide chlorthalidone chlorothiazide metolezone not so much but those are pretty generously you know decent agents in treating hypertension for patients whose non-elderly African-American there's been shown to be benefit not from the ACE inhibitors and the arbs and the reason why is patients with African-American are referred to as what's called having what's called Low renin hypertension so these patients have been studied to have low renin hypertension so therefore they will not benefit from the ACE inhibitors and the arbs so what we found is that these patients really really benefit primarily from the dihydropyridine calcium channel blockers they really respond well to that and so the categories that you want to remember for this one is the dihydropyridine calcium channel blockers tend to be the best one for these patients and then the plus or minus that you can add on here so this is amlodipine nifedipine nimodipine things of that nature the one that you can add on if they're still not reaching their goal is you could add on what next then you could add on a thiazide diuretic okay so again Hydrochlorothiazide chlorthalidone chlorothiazide these are pretty decent drugs to be able to give to these particular patients okay and then again the next one here to be able to talk about is again patients who are elderly with underlying hypertension so in these patients what I really want you guys to think about here is that this is really going to be what we've found to be the most beneficial here is patients really respond well to dihydropyridine calcium channel blockers if they're elderly again regardless of what a African-American non-african-american they found that there's most benefit from the dihydropyridine calcium channel blockers so this is the preferred agents to give in this situation and then again if the patient is not meeting goal it's important to be able to be very cognizant and think about which category would they be been most beneficial from so look through their history do they have diabetes CKD maybe they'll benefit from an ace inhibit or an R do they have some type of CAD or engine maybe they'll benefit from a beta blocker maybe they'll benefit from some other type of drug okay do they have heart failure maybe they'll benefit maybe hydralazine or isosorbide nitrate especially if they're African-American so thinking about those things and being thoughtful is really really important okay so now that we know if a patient has essential hypertension without any true cool morbidities there's four first-line agents for essential hypertension ACE inhibitors arbs thiazides and dihydropyridine calcium channel blockers if they're non-elderly non-african-american they have hypertension ACE inhibitors arbs thiazides if they're African-American non-elderly with hypertension they don't respond to ACE inhibitors arbs so dihydroperating calcium channel blockers thiazides if they're Elderly with hypertension regardless of their race dihydropoding calcium channel blockers okay now what we got to do is we have a patient who is has a history of hypertension right they have a history of hypertension their blood pressure is not being well controlled so maybe they've been on multiple blood pressure medications maybe they've been taking their amlodipine and then they recently got put on a thiazide and then maybe even they got put on an acid or an ARB but their blood pressure is not well controlled okay or maybe they're not taking their medications and their blood pressure goes up and up and up and up and it starts pumping up into the greater than 180 systolic over 120 diastolic and then all of a sudden they start having Target organ damage complications what would this look like because it's important to know what these things look like and then how to treat these patients with what agents depending upon the type of Target organ damage they have let's get over there and talk about that last situation here is we have a patient who's supposed to be on a bunch of anti-hypertensives okay they have hypertension and they're supposed to be on an Ace inhibitor or an orb they're supposed to be on their thighs eye they're supposed to be on their dihydroperating calcium channel blocker maybe they're taking a beta blocker because they have coronary artery disease or afib whatever but the whole point is they're supposed to be on these medications they're not taking it so they decide to not take it and then their blood pressure is like three thousand over twenty thousand but you get the point it's just it's stinking High and the real number that we care about is when that blood pressure is like really pumping up so greater than 180 systolic over 120 diastolic is concerning okay but really what's concerning is not just the number it's if they have Target organ damage Target organ damage Target organ damage Target organ damage is most important because that is what determines the hypertensive emergency not the number if they have no target organ damage it could be a hypertensive urgency which may be a different treatment process but if they have greater than 180 over 20 and they have some evidence of Target organ damage that is present that is a hypertensive emergency and you got to treat these patients really quickly you got to get on top of them so what does it look like well if the blood pressure skyrocketed in the head it's going to pop every vessel in the brain right so they can end up with like a subarachnoid hemorrhage they can end up with an ich they can end up with what's called Prez so look out for potential complications here such as maybe an acute ischemic stroke is potential they can rip open a plaque in the you know vessel wall an interest cerebral hemorrhage they can cause an aneurysm maybe a subarachnoid hemorrhage or maybe they can have something called Pres the biggest thing is if they present with an altered mental status we call it encephalopathy so Prez can actually cause seizures but if a patient has like an alter mental status and they're encephalopathic from their high blood pressure these are neurological emergencies that you've got to be careful of because of that BP the other thing is if it gets into the eye and it actually starts kind of causing a lot of Edema around the actual optic disc it can actually cause something called Papa La Dima so watch out for this too so this could be a potential sign here of a lot of high intracranial pressure so it could be secondary too high icps and again indicative that there's just a lot of cerebral perfusion pressure because the blood pressure is like through the roof the next thing here is if it actually has profound effects on the cardiovascular system so whenever you have a patient whose blood pressure is extremely high what happens is I want you to think about like this when the blood pressure is really really high okay whenever you have a very very high blood pressure out here in the systemic circulation that high BP correlates to a very high afterload okay and that high afterload puts a lot of strain on the heart so now this poor left ventricle is going to have to pump blood that it's getting filled with out into this extremely high pressure circulation and so if a patient's BP and their systemic circulation is through the roof the afterload is going to be through the roof and because of that it's going to make it so hard for the left ventricle to get blood out and so that increases the demand of the heart so that really really increases the demand and oxygen demand of the heart why is that a problem if a patient already has a reduced O2 Supply because they have coronary artery disease that can increase the actual ischemia if they have on top of this they have a decreased O2 Supply because they have coronary artery disease so they have a plaque within their vessel right so they have CAD because that can cause ischemia and that ischemia can lead to maybe an acute coronary syndrome so this may cause an unstable angina this may cause an nstemi these are really scary situations where it may even cause an infarct of the myocardial tissue so watch out for these particular things the other interesting thing here is that on the vessels if you imagine if the blood pressure is like so high in these vessels you're going to rip right through the vessel wall the Tunica intima doesn't stand a chance and because of that you can create this false Lumen within the vessel and so you're just going to Shear Force rip through the Tunica intima and then create this like false Lumen within the blood vessels what's that called an aortic dissection so again increased blood pressure may increase the risk of an aortic dissection so I think one potential thing to watch out for here is again any kind of myocardial ischemia any aortic dissection papillaedema neurological emergency what else this one's really interesting whenever you have a super super high afterload not only does it cause a very massive increased Demand on the heart but it makes it super impossible to get blood out of the heart as well so not only does it increase the demand and now The myocardium is like oh my gosh I can't handle this it's also going to say I can't quite push the blood out of the heart so because of that blood stays in the heart and then backs up into the lungs so because of this massive increase in afterload what this does is this decreases the left ventricular cardiac output and if you decrease the left ventricular cardiova blood is not going to go out of the heart it's actually going to back up into the pulmonary circulation and that's going to cause it to kind of leak out into the actual pulmonary interstitial spaces and cause massive pulmonary edema and so watch out because of that because it decreased left ventricular cardiac output it causes backflow and that backflow can lead to massive pulmonary edema we call this flash pulmonary edema or sympathetic crashing acute pulmonary edema so watch out for that as well so if I have a patient who's altered they have papilledema they have a ischemic heart so an nstemi or unstable angina they have flash pulmonary edema they have an aortic dissection and then what else dang blood pressure's so high I'm going to blow the renal capsules open baby so I won't stop until I got people peeing out blood and so because of that that blood pressure is going to be so high it's going to be blowing up glomeruli and causing these patients to have massive acute kidney injuries imagine you got so much blood pressure and you start blowing up those glomeruli you think they're going to work really well and give you good glomerular filtration rates no and then what's going to end up happening is you're going to have lots of red cells popping onto your urine so watch out for these patients to have hematuria and then also you're going to blow up their glomeruli so you're going to cause these patients to have a really good acute kidney injury and hematuria so watch out for acute kidney injuries and Associated hematuria with these patients if the patient comes in they got a blood pressure greater than 180 over 120 and they have any of these findings they now have a hypertensive emergency and these patients need to be treated quickly what we want to do is is we want to take the blood pressure of greater than 180 over 120 and we want to slowly titrate that down and what we want to do is maybe over a couple hours a few hours I want to drop that down to maybe I don't know 25 percent you know no greater than 25 of this that's what I want to do I want to drop it down by 25 and then over another couple hours I'll drop it down to less than 160 and then over another couple hours I'll drop it down to their Baseline blood pressure where they're supposed to be okay but that's the whole concept here is we're doing this over a certain period of time over hours to days okay it's not a process where I'm just going to be like all right they're you know 200 over 110 let's get them to 130 right now baby no you do that you drop their pressure that fast you're going to decrease the perfusion to all of these organs that have been expecting to have high perfusion you will stroke them out you'll end up with an MI you'll end up with a terrible acute kidney injury so because of that do not drop their blood pressure too quickly do it nice and slow and allow for them to be able to Auto regulate now the big question is as we talked about what agents are really good for patients in outpatient scenarios so patients who have hypertension plus this comorbidity patients who have hypertension with no cool morbidity what about the patients who have a hypertensive emergency which agents do I grab do I just do all the ones that I told here take some oral captopril and you'll be good brother no no you got to have particular agents that you know and prescribe so let's talk about those let's come down to the choices that we have there all right so you get a patient comes in they got a blood pressure of greater than 180 over 120 and now they got a big old blood pocket in their brain right so maybe they have an acute ischemic stroke so maybe they infarcted parts of like their MCA territory or maybe they have like this big old bleed sitting here in their basal ganglia or maybe they have some type of like massive vasogenic edema presenting within their posterior portions of the the brain Prez so either way there's some type of like finding of a neurological Emergency due to their high blood pressure so I just like to think about these as a neurological emergency let's actually do this in red just to you know vary up the colors so you have a neuro emergency okay whether this be due to the things that we just mentioned an acute ischemic stroke so a big infarct an ich you know Prez or you know again subarachnoid hemorrhage something of that nature I got to drop their blood pressure down so what I'd like to do is again titrate down slowly if they were like pumping up in the 200s I'm not going to drop them down to like 140 over 90 within a couple hours I got to do that slowly because I gotta allow for their brain to adjust because it's been so used to these higher profusion pressures if you drop it down oh boy are you in trouble so because of that I got to go slow and so I'd really like a very easily titratable agents that's a nice infusion and really what we've seen most benefit from and what I particularly prefer is actually nicartipine I find that the cardipine is going to be the most commonly utilized infusion because it's just nicely titratable for these patients who have some type of neurological emergency if you want to you can do PRN like IV boluses of labetalol and hydralazine but I prefer to find that I find that usually the cardipine is going to be the most situated to be best pursuited in this situation okay next one we go to the cardiovascular stuff here okay we got a patient here who has some type of unstable angina they have an end stemi okay so you have a patient here who has unstable angina or they have some type of nstemi they got some really bad you know coronary artery disease here an acute coronary syndrome kind of thing but no stemi if that's the case what I really want to do here in this particular situation is I want to reduce the demand I got to reduce the demand and my friends we've already talked about these already so here's the thing if I have a patient who has a hypertensive emergency I want to think about patients who have hypertension okay they have hypertension and they have CAD or they have some type of angina what were the drugs beta blockers calcium channel blockers nitroglycerin I don't like to use calcium channel blockers because they can really be somewhat problematic and they're not really good especially if a patient has like a little bit of a problem where their cardio their cardiac outputs a little reduced so what's actually been shown to be really really good in this situation who has unstable engine and stemi is a beta blocker so that would be the first one so again the whole goal with these is the one to reduce the Demand right so with these the whole goal is to reduce demand and so the way that I'm going to do that is one particular drug that I think is really really decent here is asthma wall so as Malone may be a pretty good infusion that you can give to people and it's easily titratable that can actually work as a beta blocker so this is a beta blocker pure beta one blocker so it's going to reduce heart rate reduce contractility and reduce demand the other one that you can give is labetalol this is not an infusion it's not a truly type tradable agent so this will be an IV push but again this is a alpha beta blocker so it may be good to be able to block the beta receptors to give you again A reduced heart rate of reduced contractility and reduce the demand but you also get a reducing after load so that may also be a somewhat benefit in these patients and the last one here is going to be nitroglycerin but I really want you to remember that this is actually going to be low dose nitroglycerin so this is low dose nitroglycerin why because nitroglycerin is actually going to work particularly I'm going to kind of highlight this one I'm going to put a blue check mark here what it's going to do is actually going to Vino dilate and because it Vino dilates what does it do to the preload it reduces the preload if you reduce the preload to the heart what do you do to the stroke volume you drop preload you drop stroke volume you drop cardiac output you drop the work or demand required by the heart plus what else does nitroglycerin do we already talked about this it takes a coronary vessel that has this plaque here all right so here's the plaque within this vessel and it can do what to the coronary vessel here it can cause coronary vasodilation so it's also pretty good because it can stimulate coronary Vaso dilation so these are drugs that we can actually give to patients who are having some type of angina unstable angina are in stemi secondary to their blood pressure being greater than 180 over 120 as a complication of that okay next one here patient has an aortic dissection so if they have an aortic dissection again the problem with this one is I really want to just reduce the amount of blood that's getting pumped out of the heart right because I reduce the amount of blood getting pumped out of the heart I reduce the amount of blood that can just keep filling into this dang aortic dissection that's really where the money's at yes if I can get a little bit of a vasodilatory effect I can also reduce the resistance but it's going to be more beneficial for me to reduce the amount of blood getting out of the left heart so what I want to do is in this situation here I want to try to reduce the actual um cardiac output is really what I prefer and then the second agent that I can add on there to give a little bit more of a vasodilatory effect a powerful arterial vasodilation would be the second thing that I can do so aortic dissections if we want to drop the cardiac output one of the particular agents that we can use in this situation is asthma wall so asthma law will actually work as again as a beta blocker and it's a great infusion that you get a really good control over you could consider labatalol as well because you'll get a combination here you'll get a combination and again it's an IV push but it is an alpha beta blocker and so you may get some benefit because it's actually going to reduce cardiac output by heart rate drop and contractility drop and also vasodilate the vessel to reduce resistance the last agent I really don't use it because of the risk of cyanide toxicity subsequent lactic acidosis and coronary steel syndrome but you could consider nitropresside but I if I'm going to use a vasodilator instead of me going with nitroproxide I would actually prefer to just go with a better vasodilator like nicartipine okay so if I'm really going with a vasodilator a pure vasodilator I'm going to go with the carbine way over Nitro peroxide first thing okay so that's what we would do for a patient it was like an acute aortic dissection okay the next situation here is someone has sympathetic crashing acute pulmonary edema or Flash pulmonary edema so they have a massive or Flash pulmonary edema I like to call it scape sympathetic crashing and keep pulmonary edema but the basic concept here is that the patient has massive increased left ventricular afterload okay and I'm having difficulty getting the blood out of the left heart so the problem is is the afterload is so dang High that because the the BP and the aortic circulation is so high I'm having difficulty in getting blood out so because of that blood is backing up into the lungs and causing massive pulmonary edema so what I want to do is I want to improve afterload so what I'm going to do is I'm going to give a drug that's going to really really reduce afterload so I'm going to give a drug that's really going to try too bring down the afterload that's really what I want it to do I want it to reduce the afterload and so the way that I'm going to try to reduce the afterload is I'm going to give a drug that it's a very powerful arterial vasodilator so you would think oh nitropresside oh no cardipine in a way yes but there's another drug that's really good because if I give it a high doses it dilates the arteries and it dilates the veins glycerin nitroglycerin so nitroglycerin is great in this situation now what nitroglycerin is going to do is it's going to at high doses high doses I'm talking like you got to get up to the 400 mic range for these sometimes maybe even higher uh yes sometimes even 800 mics but generally when you give a nitroglycerin what it's going to do is it's going to it's going to cause arterial vasodilation so it's going to decrease systemic vascular resistance that'll decrease the afterload the other thing is it's going to dilate the veins and it's going to decrease preload and so what that's going to do is if you do both of these things that's really really helpful in Flash pulmonary edema here's why if I reduce the resistance I drop the afterlid I improve forward flow at the same time if I drop preload I reduce the actual amount of blood coming into the heart congesting it even more causing more fluid to accumulate and back up into the lungs you see what I'm saying so that's a benefit to nitroglycerin is if I give this drug at high doses I get arterial vasodilation reduces afterload improves forward flow and also I can drop preload which reduces the venous return to the heart we're doing this reduces the amount of volume that's in the heart and prevents back flow back into the lungs and so this is what I could use in that particular situation uh Engineers we covered a lot with these anti-hypertensives I I truly hope that you guys you know like this video and I hope it made sense I really thank you guys for sticking around throughout this whole process but guess what we ain't done we got to do some cases if we really want to understand this and never forget it let's do some cases to cement this stuff into our brain all right guys let's do some cases so here we have a 55 year old non-hispanic male uh black male um has hypertension past medical history includes diabetes hyperlipidemia according to the ACC aha guidelines which among the choices represents the most appropriate blood pressure goal for the patient so generally the blood pressure when it's high obviously we talked about this before is that high blood pressure is characterized as generally 140 greater than 140 over 90. so having a blood pressure just below that is probably not ideal it might actually be nice to bring them down to below stage one so maybe less than 130 over 80 would be a particularly decent goal because if you bring them down to less than 140 over 90 they're still at stage 100 retention so bringing them down to like this point of less than 130 over 80 which is stage one might be beneficial obviously right so that should be kind of a target blood pressure goal for most patients is generally going to be less than 130 over 80. that should be a decent long-term goal for these patients all right all right second question here 59 year old non-hispanic white patient presents for the treatment of hypertension past medical history pertinent for diabetes hyperlipidemia and hypertension patient's blood pressure is 150 over 93 that's elevated at stage two both today and the last phase this has two blood pressure measurements that are high so that definitely kind of qualifies them for hypertension which is a recommended initial therapy to treat hypertension in this patient okay they have hypertension and then one other comorbidity that is mentioned there diabetes with diabetes what is the medications that are best I told you this because it prevents the diabetic nephropathy it would be ACE inhibitors are arbs is there an Ace inhibitor yes enalapril and so this would be the preferred agent in this particular scenario so the answer should be a nalapro because it's going to reduce the diabetic nephropathy effect and reduce proteinuria all right question three 45 year old male complains of constipation was recently started on two anti-hypertensives due to his elevated blood pressure current medications include lisinopril chlorthalidone Verapamil rasuvastatin and aspirin which is most likely contributing to his constipation so which one of the anti-hypertensives are in contributing here lisinopril has nothing to do with you know the smooth muscle particularly within the git chlorthalidone that's a thiazide varapamil is a calcium channel blocker so remember there's calcium channels that are present on smooth muscle cells that are also within the git so you can definitely cause inhibition of the smooth muscle contraction leading to constipation so Verapamil definitely is a likely cause here all right holy crap this patient's all jacked up so which antihypertensive medication can cause the rare side effect of angioedema via inhibiting the bradykinin breakdown so bradykines build build build and cause massive capillary leakage and visibility effect this would be ace inhibitor so ACE inhibitors are going to be the most common cause in this situation and the prills again that should give it away I never mentioned this on the board but it has a pearl on it so it's likely a ace inhibitor 52 year old female has uncontrolled hypertension blood pressure is you know through the roof on treatment with lisinopril she recently had an MI um her so post Mi remember that's posted my she has a past medical illustrating which includes diabetes hypertension hyperlipidemia and osteoarthritis considering her compelling indications which agent may be appropriate to add to her anti-hypertensive therapy okay post Mi and diabetes are the key comorbidities here so for postmi it was best to use beta blockers or it was also best to use ACE inhibitors and arbs but she is already on an Ace inhibitor you can't put someone on an Ace inhibitor and an ARB it's one or the other she also has diabetes diabetes again because of the progression to diabetic nephropathy these patients benefit most from ACE inhibitors or arbs but she's already on an Ace inhibitor so she's not going to benefit from an extra additional one like an ARP so because of that that leaves me with beta blockers is going to be the primary one here that's really good post Mi okay so I would consider beta blockers as the choice here in this object so quantity no almost r10 that's an ARB so we can't have an ARB and an Ace inhibitor furosemide is good for heart failure but particularly again more in situations of symptomatic control and then metoprolol that's a beta blocker so I would go with metoprolol just because it's going to give you the benefit of treating the post Mi patient all right blood pressure preparation with essential hypertension is that goal on treatment with enalapril she was since initiation of analopril the serum creatinine has increased 25 above Baseline that's pretty normal because again it's decreasing the glomerular blood pressure by causing reduction of the efferent arterial vasoconstriction so that's pretty natural for them to have a bump in their creatinine and a drop in their GFR doesn't mean that you got to stop the medication I would just continue if the patient had an acute kidney injury where she developed some problem and then on top of that she's also taking her ACE inhibitor or an ARB that's a different situation I would consider maybe holding it or you know maybe reducing the dose but in this situation the patient doesn't have an acute kidney injury she just has a mild bump in her creatinine that doesn't mean that I got to stop this so I'm not going to discontinue this I'm not going to reduce the dose I'm just going to continue the current dose of enalapril so that would be my option there if she developed a significant increase in her bu and creatinine then that's a different story and because maybe she has an acute kidney injury on top of the medication so then that may be a different story but in this situation there's no problem it's just called causing a g increase in the creatinine due to the decrease in GFR because you're reducing the glomerular blood pressure reducing the metal filtration rate which of the following correctly outlies a major difference in electrolyte disturbances associated with thiazide and Lube diuretics okay so a major difference so pretty straightforward thiazides actually increase calcium and Loops decrease calcium so any one of these that actually says that so thiazides increase calcium Loops decrease calcium that's pretty straightforward that's the main kind of electrolyte difference because they both can cause maybe a mild degree of hyponatremia but believe it or not with thiazide erratics they actually cause you to produce dilute urine so they actually may cause more of a hypernatremia especially if you're continuously continuously giving Loop Diuretics and massive doses but it can kind of cause mild hyponatremia they can drop the potassium so you're going to want to watch out for hypokalemia they can drop your magnesium so maybe a little bit of hypomagnesemia they can also cause metabolic alkalosis maybe a Teensy bit of dehydration but that's mainly you give it in patients who are pretty much of a hypervolemic or volume overloaded so that is the kind of Concepts in hyperlipidemia hyperuricemia hyperglycemia Etc but the big difference in electrolytes is calcium thiazides actually increase calcium reabsorption thiazides cause calcium I'm sorry Loops cause calcium loss so it should be D all right which can precipitate a hypertensive crisis following the abrupt discontinuation or cessation of therapy I remember I told you this one clonidine clonidine is very powerful when you think about the mechanism of action how it really helps to suppress the Central Drive of norepinephrine which can lead to Beta blockade on the heart reduce heart rate contractility Alpha blockade in the arteries decrease resistance and then also Alpha blockade on the veins decrease preload so it has a pretty significant effect there if you go ahead and just get rid of something that's suppressing the central norepinephrine release and you just stop it you're going to have a massive norepinephrine Surge and it's going to really hit those beta receptors and Alpha receptors hard and really jack up the blood pressure and heart rate so watch out for clonidine for a complete rebound hypertension really scary one which of the following is a dihydrated calcium channel block remember these are the ones that bind onto the vascular smooth muscle they primarily act on the vascular smooth muscle but they have no effect on the nodal cells or the contractile cells of the heart that is always the amlodipine nifedipine the cardipine nomodipine clavidipine so amlodipine is one of the options here Brad mil diltiazem are non-dihydropyridine so they act primarily on the heart okay the nodal cells contract our cells but they have a little bit of vasodilatory fact wrapped them more than diltiazium all right last question here 45 year old male will start on uh therapy for hypertension developed a persistent dry cough which is the most likely responsible for this side effect remember bradykines are related to this so you need an Ace inhibitor to reduce the breakdown of Brady condensate inactive metabolites increased Brady kind of causes a little bit of vasodilatory and capillary leakage activate some of the cough receptors and causes this dry cough so you're going to see this primarily with ACE inhibitors whereas the prills so lisinopril will be the answer there all right my friends this covers the cases and this completes our lecture here on hypertensive medications I really hope it made sense I hope that you guys liked it and as always until next time foreign [Music]