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I engineers in this video we're going to talk about angiotensin converting enzyme inhibitors also known as ace inhibitors as well as angiotensin 2 receptor blockers also known as ARBs so let's gonna get started are so before we start talking about the different types of aces in our was there mechanism of action there indication side effects and a couple contraindications we have to understand the renin-angiotensin-aldosterone system because if we do all the ACE inhibitors
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are ARBs are gonna do is block that normal physiology so let's briefly kind of fly through our normal renin-angiotensin-aldosterone system so how does this all work basically you have specific cells in the kidney right and they're gonna be right around the a efferent arteriole they're called the JG cells alright and these are Rin and producing cells whenever there's low blood flow or decreased perfusion through the renal artery going to those JG cells it stimulates the JG cells to release a
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specific enzyme called renin now renin is a very beautiful enzyme and what renin does is is it converts a protein made by the liver you know the liver makes a protein called angio tense intogen and what renin does is he cleaves appers a portion of angiotensinogen he cleaves a couple amino acids off of it and activates it by turning it into angiotensin one then angiotensin one run one runs through the circulatory system and goes to the lungs in the capillary endothelium of the pulmonary system
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there's another enzyme called angiotensin converting enzyme also known as ace this enzyme what it does is is it takes and stimulates angiotensin 1 cleaving off another particular amino acid sequence and converting this into angiotensin 2 angiotensin 2 is an extremely potent vaso constrictive agent so again how do we start renan due to decreased perfusion or decreased blood flow to that area that stimulates the random production from JG cells that Cleaves angio
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imogen in to angiotensin 1 angiotensin one goes to the capillary endothelial lungs where aces which converts angiotensin 1 into angiotensin 2 angiotensin 2 has multiple different effects on the body let's talk about a couple of them right one of the things you need to know is that there's angiotensin ii receptors present on the vascular smooth muscle so we have angiotensin ii receptors all right these angiotensin ii receptors that are found on the actual vascular smooth muscle
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when angiotensin binds to them it causes those smooth muscles to contract when they contract it triggers what's called so they're smooth muscle contracts and after that smooth muscle contracts the tunica media it leads to vasoconstriction you know whenever you vasoconstrict a vessel you decrease the diameter whenever you reduce diameter of the lumen of the vessel the blood flowing through that encounters more resistance if you increase total peripheral resistance you thereby
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increase blood pressure that's one way and if we increase blood pressure technically we're gonna increase blood flow through the kidney that's the whole Wiis reason this whole mechanism works the other way is that angiotensin ii is going to act on a specific area of the of the pituitary right so you know within the pituitary you have two components the anterior pituitary and the posterior pituitary angiotensin ii stimulates the posterior pituitary the posterior pituitary will release a
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specific hormone called the antidiuretic hormone the antidiuretic hormone will then go to the kidneys when it acts at the kidneys guess what it does it stimulates it puts in little aquaporin units right and by doing that it increases water reabsorption if I increase water reabsorption I technically will increase blood volume and by increasing blood volume that increases my blood pressure okay the other thing is - attention - also stimulates specific cells called the zona glomerulosa on the
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adrenal cortex and stimulates the zona glomerulosa to release what's called aldosterone aldosterone is a mineral corticoid it acts on the kidneys right particularly at the distal convoluted tubule whereas ADH works at the level of the collecting duct aldosterone acts at the distal convoluted tubules and it works to increase this watery absorption particularly by increasing sodium reabsorption by doing that if you pull more sodium and water into the bloodstream you increase your blood
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volume and if you increase your blood volume what's that gonna do that is going to increase your blood pressure the other thing that you got to remember is guess what else aldosterone does aldosterone also does something else he stimulates and when you do sodium reabsorption it also initiates potassium excretion and if there's potassium excretion in the urine then what does that mean that can lead to hypokalemia so they could have hypokalemia whenever there's too much aldosterone as well as
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hypernatremia high sodium levels and hypertension due to increased water and sodium increasing blood volume and increasing BP so now that we understand this whole mechanism of the renin-angiotensin-aldosterone axis we can just talk about how the aces and ARBs block these effects alright so now let's going to talk about the mechanism of action of these drugs it should be very simple guys let's blast through this remember there's decreased blood flow or decreased perfusion through the
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renal artery stimulates the JG cells right the JG cells respond to this by making renin the liver makes what's called angiotensinogen produced by the liver naturally renin converts angiotensinogen into angiotensin 1 by cleaving off a specific amino acid fragment now angiotensin 1 will then travel via through the blood to the cap helium of the pulmonary system where angiotensin-converting enzyme is that's interesting all right because we know about the drugs called ACE inhibitors
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well angiotensin converting enzyme we know that he helps to stimulate the conversion of angiotensin 1 into angiotensin 2 so if we use drugs like ACE inhibitors which we'll talk about the different types we're going to inhibit this enzyme if you inhibit the ACE enzyme then are you going to be able to convert angiotensin 1 into angiotensin 2 no so that means that you'll have a decrease in angiotensin 2 well let's think about this then it has three primary effects that we focused on
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previously right one is it acted on the blood vessel right particularly on those angiotensin 2 receptors remember these whenever it acted on it primarily caused Vaser constriction but you're not gonna have these or constriction out you're gonna have the opposite because it's opposing this that's gonna lead to vaso dilation vasodilation is going to lead to what a increase in the diameter of the lumen so now there's less resistance that blood is going to encounter and if there's less resistance
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that's gonna drop the blood pressure that's pretty cool second thing angiotensin normally stimulates the posterior pituitary right the posterior pituitary to make ADH now if you are having decrease angiotensin 2 you're not going to stimulate the poster pituitary as much there's going to be decreased ADH production if there's decreased ADH production what does that mean to the kidney that means that there's gonna be less water being reabsorbed if there's less water reabsorption that's gonna
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result in a drop in the blood volume and a drop in the blood is gonna result in a drop in the blood pressure hmm what else if we actually inhibit particularly another area the zona glomerulosa remember the zona glomerulosa was responsible for making the hormone called aldosterone now if there is less angiotensin 2 there's less stimulation of aldosterone so there's a decrease in the production of aldosterone less aldosterone means that you're gonna have less what there'll be a decrease in
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sodium and there'll be a decrease in water reabsorption and if there's a decrease in this that means that there's a decrease in the blood volume and therefore a drop in the blood pressure in addition you're also going to be inhibiting al bostrum mber it reese's the sodium and water reabsorption right but if we and then also by doing that it causes a potassium excretion remember we said that previously well if we block that effect we're not going to excrete the potassium as much
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so now potassium could potentially build up in the blood and that could lead to hyper Kaleem iya which is a potential side effect of ACE inhibitors so we know how a sin hitter's will work what about angiotensin ii receptor blockers where does han gyeo Tencent to receptor blockers work at all of these sites so if I give an ARB it's going to inhibit this reaction if I give an ARB it's going to inhibit ADH production if I give an ARB it's going to inhibit aldosterone production do you see how
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that all works now another thing you have to realize is that whenever there's vasoconstriction right whenever there is vaso constriction what does that do right it increases total peripheral resistance whenever you increase total peripheral resistance what does that do to the afterload it increases absolutely right theoretically because now the pressure is going to build up proximal to wherever that constriction point is well that's gonna put stress on heart okay
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it's gonna stress the heart and if someone has heart failure if someone has coronary artery disease where their oxygen demand is already really low and you don't want to increase the stress on the heart even more or if someone has very strong normal vasoconstriction like they have a very strong isolated systolic hypertension wouldn't these drugs be painted pretty beneficial like ace inhibitors and ARBs why because they decrease angiotensin ii production right
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so think about this now if we give okay let's go back to angiotensin ii it caused vasoconstriction right if we give an ACE inhibitor or we give an ARB what are these going to do they're going to lead to a decrease in angiotensin 2 production that's going to result in less vasoconstriction if there's less phase of constriction there's a drop in the total peripheral resistance there's a decrease in the after load and therefore a decreased stress on the heart and that beautiful way that works
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in the same way you guys remember angiotensin 2 also did something else right it led to increase ADH and increased aldosterone and if you remember both of these collectively increase sodium and water which increases blood volume well if you have more blood circulating through the heart what does that do to your preload the amount of blood that's returning back to the heart it increases because you have more blood volume that means an increase in the preload and if you increase the preload
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technically you can increase the edv and by increasing the edv you technically if the heart is already stressed already from heart failure from having hypertension from maybe a previous myocardial infarction coronary artery disease something like that it can put more stress on the heart so by doing that you increase the stress on the heart right so well let's put an up air here and now let's try to make sense of it all if you give an ACE inhibitor or ARB what do you technically do well you
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decrease angiotensin ii whether it's decreasing production or blocking at the receptor sites so that's going to lead to what for the ADH it's going to lead to decreased production of ADH decrease production of aldosterone that technically leads to a decrease in the sodium and water reabsorption collectively more specific sodium fraud Ostra water more specific for ADH but either way the whole of as a result is the same you decrease sodium in water you decrease blood volume you decrease
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blood volume do you decrease the preload on the heart you decrease the preload you decrease the EDV and you potentially can decrease a lot of that extra stress on the heart so I should make so much sense now why these drugs are really good all right so now let's go ahead and talk about the different types of ACE inhibitors and ARVs all right so now let's go ahead and talk about the different names of a lot of these ACE inhibitors that you might see or angiotensin ii receptor blockers that
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can come up so names the best way to remember the ACE inhibitors is they usually end in prill so just like beta blockers and in a wall the ACE inhibitors will end in pril so what are some of them Benza pro captopril enalapril and lisinopril so these are some of those ACE inhibitors angiotensin converting enzyme inhibitors now angiotensin ii receptor blockers again they're pretty much the scene just like ACE inhibitors they're pretty great drugs it's just we'll talk about in a
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second that usually only time you use a arby's is if ACE inhibitors are not working for a patient and we'll talk about why yours is because of like angioedema or a dry cough so angiotensin ii receptor blockers these ones usually end in tan so this would be like Kanda's our tan so you see that tan at the end lows are 10 and Val's are tan okay so these ones again angiotensin ii receptor blockers so ACE inhibitors Benza Pro captopril enalapril is in April if you forget them just remember the end
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in Pearl angiotensin ii receptor blockers Kanda's are ten lows are ten valsartan if you forget them remember they end in tan okay it's easy whatever comes up on an exam to remember that all right now that we know the name of the drugs their mechanism of action let's go into their indications alright so let's talk about the indications here we know that they're great and basically helping to reduce blood pressure now obvious and a lot of the mechanism of action right so if it's good in dropping
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blood pressure what kind of condition do people have when they have high blood pressure it's called hypertension right so it's great for people with hypertension okay now it's a it's important to mention that there is patients african-americans as well as older individuals who have what's called low renin hypertension so in other words their angiotensin ii isn't super super high so because of that these kinds of drugs aren't really super beneficial for that population so
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if you are having someone who's like african-american their or their Caucasian who have a lower rent and hypertension they're probably gonna respond better to diuretics or calcium channel blockers like nifedipine or amlodipine but either way hypertension is one of the indications for this because it can draw pressure the other thing is it's great for us remember we said that if you can decrease after load that can decrease some of the stress on the heart there's
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two good reasons why you would want that what if someone has an underlying coronary artery disease or they recently had an MI it can be good for that because their heart is already stressed decreasing that stress and then oxygen demand will help to benefit that so that would be one thing if someone has coronary artery disease and more specifically let's just say that they had a recent or previous mi these are actually beneficial drugs for that after some of that in MI the next thing is if
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someone has heart failure why if someone has heart failure and you try to reduce that afterload that's very helpful especially if someone has systolic heart failure because the pumps already weak if you decrease the after load it's gonna make it a little bit easier for them also for heart's already weak and you try to increase the oxygen demand on them that's gonna make it worse because give you're giving them more preload you're giving them more after load
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that's going to really stress that weak heart out so if you reduce the preload reduced the after load reduce the oxygen demand they can really make a big difference in heart failure it's one of the first-line treatments another thing that we've also seen with ACE inhibitors and a arby's is that they're good for patients with kidney disease particularly those who have a lot of protein uric kidney disease so one of the big ones here is diabetes so if someone has diabetic nephropathy
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right in diabetic nephropathy they lose a lot of protein in their urine right they get they lose a lot about booming in the urine so what we can do is we can give ace inhibitors and a RPS and what they've been found to do is actually decrease some of that protein in the urine and that's pretty cool that is very very beneficial you decrease the protein within the urine that's very effective it helps to help decrease the continual damage from it so it's nefra
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protective another way and patients who have diabetes so if someone has diabetes and you want to protect their kidneys from losing a lot of protein you can give ACE inhibitors a hair piece they're really good for that all right next thing let's talk about another thing called cardiac remodelling okay so whenever someone has had a heart attack they have heart failure or they have chronic hypertension it can cause cardiac remodeling right and that can be bad on the heart it makes it puts a lot
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of stress and heart increase a lot of fibrous tissue formation overall it leads to a decrease in the pumping function of the heart and this is especially important after a heart attack okay so let's talk about this remember that we talked about remember the kidneys they make renin right renin if you guys remember will convert angiotensinogen made by the liver right so you have angio tense intogen it'll convert this into angiotensin 1 angiotensin 2 will then get converted
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via the enzyme ace and the capillary endothelium of the lungs into angiotensin 2 and this will stimulate aldosterone production and they'll stimulate ADH production we know that regardless increase aldosterone production and increase ADH production result in what we already kind of talked about this it's that there is an increase in sodium reabsorption and an increase in watery absorption what does that do to the blood volume as a result that's going to increase the blood
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volume and that can increase preload and if we increase preload what do we do to the heart we increase the stress on the heart right on an already weak heart same way remember that angiotensin ii can also act directly on those blood vessels right and what does it do it causes vasoconstriction the overall effect of vasoconstriction is an increase in total peripheral resistance and that increase is afterload and if we increase afterload again you increase the stress on the heart any increase in
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afterload or any increase in preload in an already weak heart can it induce what's called cardiac remodelling what we want to do is to reduce that cardiac remodeling so how do we do that we give ace inhibitors in a arby's why because that decreases angiotensin ii production that leads to a decrease in the total peripheral resistance a decrease in the afterload and a decrease in that stress on the heart at least the decrease aldosterone production decrease in ADH whereas
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results in a decrease in sodium decrease in water increase in blood volume decrease in preload and an overall decrease in stress on the heart if we decrease afterload and preload what do we do we decrease cardiac remodeling so again this is one of the beneficial things of ACE inhibitors and ARBs is they decrease afterload and they decrease preload and again this goes hand-in-hand with cardiac remodelling these are great for those who've had m eyes because it helps to decrease a lot
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of the remodelling after there's a been a myocardial infarction or someone has chronic hypertension these are the indications for ACE inhibitors and ARBs now let's go ahead and talk about some of the potential side effects all right so now side effects let's make this very simple we Martin you guys will never forget this mechanism right kidney the kidney makes renin ranan is actually going to cleave angiotensinogen into angiotensin one ace will convert angiotensin one and han gyeo Tencent -
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that stimulates aldosterone production right we're gonna focus primarily on Knob Noster I'm going back to what we said about aldosterone what does it do to the kidney it increases sodium reabsorption and it increases water reabsorption right and that's eventually going to lead to an increase in blood pressure through increase in blood volume but what else do we say could do it causes potassium excretion and if we excrete potassium what does that do the blood potassium
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levels it decreases hypokalemia when we give an ACE inhibitor or an ARB we basically decrease angiotensin ii production decrease aldosterone production or block angiotensin 2 on aldosterone act producing a dosterone regardless whether it be ace inhibitor or blocking angiotensin 2 stimulating production of aldosterone decrease in aldosterone results in less sodium and water reabsorption can result in a drop in blood pressure but also it leads to less potassium being excreted and so the
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potassium can potentially build up in the blood stream what's that called hyperkalemia so potential side effect of being put on an ACE inhibitor or an ARB is hyperkalemia and that's important to make sure that you monitor because it can lead to severe dysrhythmias one of the classic signs is like peaked t-waves the next thing is potentially think about it you put on an antihypertensive drug if you give too much of it what's another potential side effect hypotension so you could potentially
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drop the person's pressure as well all right so the last side effect that I want to talk about that you commonly see with ACE inhibitors not a are B's is angioedema which is a severe reaction to ace inhibitors we'll talk about another thing that can increase the risk of that hereditary condition as well as a coffin dry cough in order for us to understand that we have to go through this brainy kind of pathway so really quickly I'm gonna take you guys through it there's a
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molecule a protein called precal Chiron okay and pre-cal Chiron is converted into callek iron right through specific enzymes that regulate that step one of the enzymes is called a see one aster ace inhibitor and the other one is going to be called factor twelve okay right which is a protein from the coagulation cascade the factor twelve wants to stimulate this pathway whereas the AC one Esther ACE inhibitor wants to decrease the activation or formation of Cala Chiron now if Callie
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Chiron is made Cala Chiron is an enzyme that converts what's called high molecular weight kine Inogen into what's called Brady Kainan bradykinin works by causing a couple different effects one is it can work on the vascular smooth muscle within the bronchioles and induce what's called bronco constriction and what that can do is is that can make it can cause a respiratory difficulty you can cause COFF and it can cause respiratory distress right because if you're
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constricting those bronchioles you're making it hard for air to get in the other thing is it can increase capillary permeability as well as vasodilation so you're gonna get an increase in cap permeability and you're gonna get an increase in blood flow to that area the collective effect here is going to be edema and swelling right and that's what happens I'm within the upper respiratory tract and within the lower respiratory tract potentially the other thing is
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that this Brady kinda can also stimulate certain nerves in lead to pain so you can get a coffee you can get angioedema here which is this edema factor to increase basal dilation capillary permeability fluid leakage and therefore deema as well as pain and coughing a little bit of respiratory distress there's another molecule that's very important that regulates the activity of bradykinin and that is called angiotensin converting enzyme guess what this enzyme does to it it tries to
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inhibit brainy kind of production if I give an ACE inhibitor guess what else I do here an ACE inhibitor if I give one will inhibit this ACE enzyme right if I inhibit ACE enzyme I'm no longer going to be able to inhibit Brady kind and production so now Brady kind and production will be stimulated if I lead to high Brady kind and production that's gonna increase Bronco constriction leading to COFF it's gonna increase capillary permeability and vasodilation leading to angioedema potentially and
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also it can increase pain here's another thing that's also interesting remember this enzyme c1s trace and hit inhibitor there are certain people who have an autosomal dominant condition where they have a deficiency in that c1 ester ACE inhibitor if there is less of this c1 s trace inhibitor what does that mean that means you're not going to be able to inhibit the conversion of precalc higher into cala Chiron that means that this will lead to increased stimulation so I'm gonna have increased
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cala Chiron which is going to convert a lot of high molecular weight kine antigen in to increase bradykinin that increases bronchospasm increases edema and increases pain now if someone has a c1 ester ACE inhibitor deficiency and they're on an ACE inhibitor could you imagine how severe this could be that's a potential contraindication of the drug if someone having a c1 ester ACE inhibitor deficiency so big side effects that I want you to remember hyperkalemia
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hypotension and with ACE inhibitors it can lead to cough or angioedema and it's contraindicated and they see one ester ace inhibitor deficiency alright so last thing I want you guys to remember is contraindications to using aces and ARBs obviously one is angioedema if you give someone an ACE inhibitor they have angioedema you can't give it again we already talked about that the next thing that you have to also be aware of is that if someone is pregnant you can't
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give this to pregnant patients the reason why is it's been shown to lead to congenital malformations so it's potentially Oh genic so instead of putting them on an ACE inhibitor or an ARB put them on something else maybe hydralazine maybe methyl dopa maybe nifedipine maybe labetalol okay the other thing is drug interactions obviously some people aren't going to respond just to an ACE inhibitor RNA RB some people might need multiple hypertensive medications if that's the case you just have to be
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careful because obviously as you give more antihypertensive drugs there's a risk of hypotension it's not something also to be aware of the other thing is that you don't want you want to be careful with what's called potassium sparing diuretics like sprint a lactone why because spironolactone if you guys remember what does it do it's an aldosterone antagonist it basically blocks the effect of aldosterone if you block the effect of aldosterone at the kidneys you're not going to be able to
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excrete potassium potassium builds up if you have an ACE inhibitor in them on spurinna lacto and that could potentially increase the potassium enough to cause severe hyperkalemia so you have to be wary about high potassium when putting them with an ACE inhibitor or ARB and a potassium sparing Durrett ik the other thing is NSAIDs in sets might counteract everything you try to do with an ACE inhibitor because they might increase sodium and water retention I do increase sodium and water retention
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you increase blood volume and therefore blood pressure so I can have that counter active effect the other thing is lithium so lithium used in bipolar disease when you give ace inhibitors or arabes it actually has the ability to decrease the elimination of lithium and so lithium levels could potentially build up that's another thing to watch out for lastly if we talk about specifically if someone has plaque development within the renal artery supplying the kidney what's that called
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they have stenosis our narrowing it's called renal stone of renal artery stenosis what if they have bilateral renal artery stenosis that would be one reason why the other thing is is if someone has kidney failure really bad kidney failure and severe chronic kidney disease we have to be careful with ACE inhibitors na are B's because they could potentially make things worse okay so these are the contraindications and drug interactions to also be aware of last but not least we talked about
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this just briefly before if someone has an autosomal dominant condition meaning they have one mutant copy and one normal gene on the two different types of chromosomes they can have what's called a c1 as strace deficiency so in c1 aster ace inhibitor deficiency which we already talked about previously you do not want to give somebody a syn hibbett errs alright so I just want to quickly explain last thing here is why if you put someone on ACE inhibitor or an ARB
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would it be bad or contraindicated if they have severe chronic kidney disease or renal artery stenosis think about it you're given a mesa Tibbett or an ARB what are you doing you're basically inhibiting angiotensin ii production angiotensin ii does what it causes vasoconstriction which increases blood pressure which increases perfusion to different organs like the kidneys the other thing is that you're going to be decreasing angio dosterone production and decreasing ADH production
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that's decreasing blood volume less blood volume means technically less blood pressure and less profusion to the kidneys so if the kidneys aren't getting enough blood flow already and you decrease their blood flow and even more by giving them an ACE inhibitor an ARB it can worsen their already chronic kidney disease or worsen their renal artery stenosis and that's not something that we want to do ionizer so in this video we talked about ACE inhibitors and a arby's I hope this video made sense I
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hope you guys did enjoy it if you guys did please hit that like button comment on the comment section and please subscribe also you guys get a chance down in the description box we have links to our Facebook Instagram and patreon go ahead and check those out i'm Isner's as always until next time [Music]
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