Antihypertensive Drugs

0:02foreign

0:07engineers in this video today we're

0:09going to be talking about

0:09anti-hypertensive medications there's a

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0:35right without further Ado let's start

0:36talking about antihypertensives though

0:37so we talk about anti-pretense what I

0:40want to do is I want to break them into

0:41four categories okay and I want to go

0:42within these four categories I want to

0:44talk about the mechanism of action I

0:46want to talk about the drugs that are in

0:47that category and then we'll also

0:49discuss some of the adverse effects that

0:50they may have because I think it makes

0:52sense to cover them when we talk about

0:53their mechanism of action

0:55all right so these four categories is

0:57sympatholytics diuretics renin

1:00Angiotensin aldosterone Inhibitors and

1:03then lastly is your vasodilators all

1:05right sympatholytics they're inhibiting

1:07the sympathetic nervous system that's

1:08the whole concept right now we're going

1:11to go through these in a couple

1:12different ways now the first one here is

1:15we're going to talk about the centrally

1:16acting drugs so there's two Central

1:19acting drugs that I want you guys to

1:21know and these two Central acting drugs

1:25are called clonidine

1:28so one is called clonidine

1:31and the other one is called Alpha

1:34methyl

1:35dopa

1:38now

1:39these two drugs are really interesting

1:41okay what do I mean by they're centrally

1:42acting

1:44you see these nerves coming from the

1:45thoracic part of the spinal cord this is

1:47your sympathetic nerves and the

1:48sympathetic nerves that go from the

1:49thoracic part of your spinal cord they

1:50actually go and release norepinephrine

1:52onto the heart and onto the blood

1:53vessels right and whenever they release

1:55norepinephrine onto the heart we know

1:57that it increases heart rate it

1:58increases contractility we'll talk about

2:00that a little bit in a second it also

2:02works on the arteries to squeeze the

2:03heck out of them and increase resistance

2:05and it squeezes the veins to increase

2:06blood return to the right heart so all

2:09of these things are working to in

2:10general to increase blood pressure in

2:12that concept well if I give a drug that

2:15has the ability to maybe suppress the

2:18Central Drive that causes the

2:20sympathetic nervous system to release

2:21norepinephrine so here's these thoracic

2:23spinal cord nerves they're releasing

2:25from these nerves lots and lots of

2:28norepinephrine and the norepinephrine

2:30work on the heart and it'll work on the

2:31blood vessels and what it's designed to

2:33do is this Central process here is that

2:36when you have an increase in

2:37norepinephrine it's going to increase

2:39heart rate it's going to increase

2:41contractility

2:44it's going to increase systemic vascular

2:47resistance and it's going to increase

2:49preload and all of these things if you

2:52think about it you increase heart rate

2:54you increase cardiac output you increase

2:55contractility you increase cardiac

2:57output you increase resistance you

2:58increase blood pressure you increase

3:00preload you increase cardiac output and

3:02then we know that the formula is that

3:05blood pressure is equal to cardiac

3:07output times systemic vascular

3:09resistance you increase resistance you

3:12increase blood pressure you increase

3:14cardiac output you increase blood

3:16pressure so what I need to do is I need

3:18to give a drug like these ones quantity

3:21and Alpha methyl dopa and what they will

3:23do is they have the capability of

3:25inhibiting all of these processes they

3:28can relax the arteries that reduce the

3:30systemic vascular resistance they relax

3:32the veins that reduces preload they can

3:35inhibit the actual heart from beating

3:37fast and Contracting fast that will

3:39reduce the heart rate and contractility

3:41all of these things will reduce cardiac

3:42output reduce systemic vascular

3:44resistance and reduce blood pressure now

3:46you're probably wondering okay they do

3:47that but how

3:49these nerves when they release

3:51norepinephrine onto the heart and the

3:52blood vessels they work through

3:54particular processes right we already

3:55talked about that but here in the

3:57central nervous system there's this

3:59Central Drive for the sympathetic

4:00nervous system so what I want to do is I

4:02want to take like this particular area

4:03here and I kind of want to zoom on

4:05because this is the thing that's really

4:07driving your sympathetic flow so if I

4:10have an ability to inhibit this process

4:12right here I may lose the sympathetic

4:15flow or outflow to the heart and the

4:17blood vessels right so let's say that we

4:19take that

4:20and we zoom in on it okay so this right

4:23here is going to be this type of

4:24interaction

4:25now here this neuron has vesicles

4:28containing norepinephrine and when this

4:31nerve is stimulated right it fuses with

4:33the cell membrane and starts plucking

4:35out norepinephrine into the synapse

4:37norepinephrine will then bind onto these

4:39receptors and then stimulate

4:42flow via the sympathetic outflow so

4:44it'll stimulate sympathetic nervous

4:46system outflow

4:48now imagine I give a drug like Clonidine

4:51continent is really interesting because

4:54what clonidine will do is it'll bind

4:55onto these receptors on the synaptic

4:57terminal these are called Alpha 2

5:00receptors

5:01clonidine is a alpha 2 receptor and

5:06Agonist so it's going to stimulate the

5:09Alpha 2 receptor now you're probably

5:10like okay that's interesting

5:11when this clonidine stimulates the Alpha

5:142 receptor so it's going to stimulate

5:15this particular receptor this receptor

5:18is responsible for inhibiting

5:20norepinephrine from fusing with the cell

5:22membrane then what happens to the

5:24norepinephrine that gets released it

5:26reduces what happens to the stimulation

5:28of the sympathetic nervous system it

5:30becomes

5:31inhibited you lose the sympathetic

5:33outflow if you lose the sympathetic

5:35outflow what happens to the

5:36norepinephrine released towards the

5:38heart it's reduced what happens to the

5:40ability to stimulate the heart rate you

5:42lose that you inhibit the actual heart

5:44rate from going up you inhibit the

5:46contractility what happens to the

5:48outflow on the arteries

5:49you lose the ability to constrict so

5:51they relax

5:52and what happens to the venal

5:54constriction you lose it so therefore it

5:56relaxes and you see how this drug has

5:59the ability to do all of these things

6:01now quantity and is believe it or not

6:03even though you would think holy son of

6:05a gun it does so many things it has to

6:07be like a first-line agent believe it or

6:09not it's not a first-line agent it's not

6:11commonly utilized to be honest with you

6:13it's more of like a third line agent if

6:15you really need it the real true

6:17indication of why we would use the

6:18struggle we talk about a lot more in the

6:20adrenergic Agonist lecture

6:22is that this is good for kind of like a

6:24patient who has withdrawal symptoms so

6:26the patient who's just recently been on

6:27a bender on alcohol benzos or some type

6:31of other situation like um usually

6:33alcohol benzodiazepines are the big ones

6:36that are usually the primary problems

6:37are opioids and they withdraw and when

6:40they withdraw they develop a massive

6:41tachycardia they develop hypertension

6:44they squeeze on their blood vessels so

6:46if I give this drug when I actually

6:48inhibit that sympathetic outflow I could

6:51treat the withdrawal symptoms so that's

6:52the true really only indication of when

6:55we would give clonidine is that this

6:57drug can really be good

6:59and situations of withdrawal symptoms so

7:02withdrawal and particularly withdrawal

7:05from specific medications because what

7:08this does is when you withdraw you have

7:10a massive sympathetic outflow because

7:12you've been suppressing that outflow

7:14with depressants like alcohol such as

7:17benzodiazepines such as opioids and when

7:19you remove that suppression now you have

7:21nothing but sympathetic outflow and so

7:23you can inhibit that by giving clonidine

7:25that's the really the only true

7:27indication but because it has the

7:29ability to suppress your central kind of

7:32norepinephrine drive it also may lead to

7:34sedation so one of the adverse effects

7:37to watch out for with clonidine is watch

7:40out for Sedation it can make the patient

7:42a little bit more sedated

7:44all right Alpha methyl dopa doesn't

7:47actually work through the Alpha 2

7:48receptors what it does is Alpha metal

7:51topa is an interesting drug here so

7:54imagine here's Alpha methyl dopa it goes

7:56through the pathway that's used to make

7:58norepinephrine and what it does is it

8:01actually inhibits you from actually

8:02truly making norepinephrine so in order

8:05to be able to make norepinephrine you

8:06know any tyrosine and then l-dopa and

8:09then dopamine and the norepinephrine the

8:11alpha methyl dopa kind of Alters the

8:13synthesis of norepinephrine and so then

8:16you have less norepinephrine in these

8:17vesicles less norepinephrine released

8:19and less sympathetic outflow because of

8:21that so it's a pretty interesting drug

8:22and really the only indication of why we

8:24would give this drug we'll talk about a

8:25little bit later is pregnancy

8:28uh one particular thing that is weird

8:31with this drug is that it may actually

8:33cause a positive Coombs test and so you

8:36may see that if a patient develops like

8:38a little bit of anemia and you send off

8:40a what's called a Coombs test they may

8:42come back Coombs test positive which may

8:44make you think about an autoimmune

8:46hemolytic anemia but this is one

8:48particular category of drugs so one

8:50category of drugs for the sympatholytics

8:52I'm going to put here let's do it in

8:54pink so that we see it here is your

8:56central acting

8:58drugs and again this is Clonidine and

9:00Alpha methyl dopa they work to suppress

9:03they're working right here to suppress

9:06the central sympathetic outflow so they

9:09reduce the norepinephrine being released

9:11on the heart and on the blood vessels so

9:13it inhibits heart rate inhibits

9:15contractility inhibits arterial

9:17vasoconstriction and inhibits venal

9:19constriction all of these things do the

9:21following that's the whole concept here

9:23because we're inhibiting this massive

9:26release of norepinephrine all right

9:28beautiful let's come to the next part of

9:31the drugs for some patholytics the next

9:33thing is that we have beta receptors

9:34that are present on the heart we know

9:36that that's the primary receptors right

9:37so if we look here let's say that these

9:39are these sympathetic neurons right here

9:41so these are the sympathetic neurons and

9:42again what are they pumping out here

9:44they're pumping out what type of

9:45molecule noro epinephrine so they're

9:48pumping out norepinephrine and you know

9:50there's another molecule another

9:52technically hormone neurotransmitter

9:54that's also released from the

9:55sympathetic nerve system it's

9:56epinephrine because your sympathetic

9:58nervous system also stimulates the

9:59Adrenal medulla and pumps that up in

10:01effort but nonetheless norepinephrine is

10:03released from these nerves

10:04when norepinephrine is released from

10:06these nerves onto the heart

10:08in order for them to exert their effect

10:09they need a particular receptor you know

10:12what this receptor is

10:13the son of a gun that's an interesting

10:14receptor this is the beta receptors what

10:16are these receptors here these blue

10:18little things popping off of these cells

10:20are called beta 1 receptors what is this

10:23one this is a beta one receptor in order

10:26for norepinephrine to exert its effect

10:28so we already inhibited norepinephrine

10:31release the central suppression which

10:34inhibited norepinephrine release that

10:36was these two drugs but what if

10:37norepinephrine is still released how can

10:39we block its effect on the heart

10:43so we can give particular drugs that

10:46will block the beta 1 receptor they'll

10:49bind onto the beta 1 receptor and

10:50prevent norepinephrine they'll be like

10:51hey get out of here you can't bind here

10:54what are those drugs not hard to imagine

10:56here

10:57the second category of drugs that we're

10:59going to be discussing here let's put

11:00them over here

11:02second category of drugs is going to be

11:04beta blockers but I want to be very very

11:07specific okay so beta

11:09blockers and really these are cardio

11:12selective so mainly these are primary

11:14beta 1 blockers

11:17now what these drugs will do is if we

11:20take the two cells of the heart so we

11:21have here your SA node your AV node your

11:24bundle of hiss your bundle branches and

11:26then um from there we go into your

11:28purkinje system right all of those

11:30things are controlling your the

11:31conduction of electrical activity

11:33on those cells these black cells here on

11:36the heart that's your nodal cells they

11:37have beta 1 receptors and then here on

11:39the red cells here the contractile

11:41portion the ones that actually squeeze

11:42and pump blood out of the heart those

11:44ones also have beta 1 receptors

11:46so if I give a beta blocker

11:49what I'm going to be doing is I'm going

11:51to block norepinephrine from being able

11:53to exert its effect I'm going to put

11:55produce an opposing effect I'm going to

11:57inhibit the nodal cell from being able

12:00to fire

12:00and what that's going to do is that's

12:02going to suppress the patient's heart

12:04rate

12:05that's going to drop there cardiac

12:08output and then subsequently it's going

12:09to drop there blood pressure oh man

12:12that's good

12:13I'm going to also give this particular

12:15drug these beta blockers so this is

12:17going to these beta blockers will

12:19inhibit the nodal cell from firing but

12:21it'll also inhibit the actual

12:22contractile cell from squeezing so then

12:25because of that you decrease

12:26contractility

12:28and if you decrease contractility what

12:31you know about that is that that drops

12:33stroke volume and then subsequently

12:35cardiac output and that drops blood

12:38pressure so this is the way that we

12:40could treat a patient's hypertension by

12:42reducing the amount of blood that

12:44actually leaves the heart and that would

12:46be the job of these beta blockers

12:48now there's many different agents here

12:51some of these that are very particular

12:53that I want you guys to know is what's

12:55called Atenolol so Atenolol is a

12:57commonly utilized one another one is

12:59called a bisoprolol

13:02bisoprolol

13:04another one is called esmolal very

13:07commonly utilized one especially in IV

13:09formulations and hypertensive

13:11emergencies and another one is called

13:12metoprolol

13:14now these are the most commonly utilized

13:17ones that you're going to be seeing

13:18particularly for the beta 1 blockers

13:21there is other ones that are

13:22non-selective like propanolol and

13:24natalol but we don't commonly utilize

13:26that in that particular situation they

13:28do have some beta 1 block K but I want

13:30you to remember these primary ones here

13:32okay that's our beta blockers now one of

13:37the things I want you to think about

13:38here don't be confused with this these

13:41drugs we're going to talk about they're

13:42very commonly used in a lot of comorbid

13:43conditions but if I'm giving a drug that

13:45has the ability to drop the patient's

13:47heart rate what's a potential adverse

13:49effect out of this it's not hard to

13:51imagine my friends

13:52adverse effects that you really want to

13:54be careful with with these drugs is that

13:56you can drop the heart rate down too

13:57much what is that called bradycardia so

14:00watch out for bradycardia for these

14:02particular drugs the other thing that

14:04you want to be careful of is that they

14:06can really drop your contractility and

14:09so if they reduce the contractility they

14:11can actually drop the patient's blood

14:13pressure where you really if a patient

14:15already has a weak heart and it's not

14:16getting a good cardiac output and then

14:18you drop the cardiac output even more by

14:20dropping their contractility that could

14:22put them in at risk of cardiogenic shock

14:23and that's the patients who have weak

14:26Hearts already so watch out for

14:28hypotension with the potential of it

14:30even causing shock and what patient

14:33population watch out for this in

14:35patients with decompensated heart

14:38failure I'm going to dhf decompensated

14:41heart failure do not give this to these

14:43patients you will kill them

14:45potentially all right the other thing

14:47with these drugs you know what a

14:50patient's hypoglycemic you know when

14:52they're hypoglycemic so let's say that

14:53your sugar drops down to like 25 right

14:55okay and when your sugar drops naturally

14:58what your body does is says hey hey

15:00sugar's low my cells ain't feeling too

15:02well and so because of your sympathetic

15:04nervous system goes into hyperdrive and

15:06it tries to let you know hey man

15:07something is not right and it makes you

15:09tachycardic it makes you a little bit

15:11kind of diaphoretic and so it makes you

15:13aware that something is not right and

15:15then you should check your sugar levels

15:16if you have diabetes

15:18when you give a beta blocker you block

15:20the tachycardic the

15:23hypertensive you block the diaphoretic

15:26type of response that sense of impending

15:28doom all of those things that come from

15:30the sympathetic response from

15:32hypoglycemia you don't have and so

15:34because of that this can really blunt

15:36that effect and so you want to watch out

15:38for what's called hypoglycemia

15:42unawareness

15:44okay beautiful beautiful

15:46all right that's our beta blockers okay

15:48the next category here is if we look

15:52here on the arteries

15:54and on the veins they have another type

15:56of receptor so here this is your

15:58arteries here so I'm just going to

15:59denote that this is going to be the

16:00arterial system coming from that left

16:01heart

16:02and then here is going to be the venous

16:05system going back to the right heart

16:07what I want to do is I want to take some

16:09particular cells from the vein a

16:11particular cells from the artery and

16:12zoom in on them here so here's an

16:13arterial smooth muscle cell here's a

16:15venous blue muscle cell and remember

16:16they all have sympathetic innervation we

16:19talked about that this is those

16:20adrenergic neurons and what are they

16:22pumping out what are they pumping out

16:23again I've already told you this you

16:24guys should know this right

16:25norepinephrine they're pumping out

16:27norepinephrine so we suppress the

16:29norepinephrine release from clonidine

16:32Alpha methyl dopa there is other drugs

16:34out there we just don't use them called

16:35Reser Pine and there's some other ones

16:37out there as well that we just don't use

16:39in the ganglion blockers Etc but if we

16:42inhibit the norepinephrine release

16:44all right that would be the quantity

16:45Alpha metadopa we can block the beta 1

16:48receptors guess what guess what these

16:49receptors are on the arteries and veins

16:51Alpha One receptors these are called

16:54your Alpha One receptors that are

16:57present both on the arterial smooth

16:59muscle cells and alpha-1 receptors

17:01present on the venous move muscle cells

17:03so if I give a drug guess what this drug

17:06category would be alpha blockers

17:10man we good so if I give a drug category

17:13like an alpha

17:14blocker what's the benefit of giving

17:17alpha blockers so alpha blockers is

17:19going to be my

17:22third category of drug

17:25okay third category drug alpha blockers

17:27are going to be interesting because if I

17:30give a drug like an alpha blocker what

17:31they're going to do is they're going to

17:32block the effect of norepinephrine and

17:34epinephrine from binding on to these

17:36alpha 1 receptors on the veins and on

17:38the arteries the effect on the artery is

17:40that you're going to relax the smooth

17:42muscle it's going to inhibit the smooth

17:43muscle from Contracting right it

17:45inhibits the GQ process and because of

17:49that it'll actually cause the muscles to

17:50relax

17:51if they relax the entire vessel will

17:54undergo vasodilation so if it relaxes

17:57and undergoes vasodilation

18:00and if it vasodilates it drops your

18:03systemic vascular resistance and that

18:05will subsequently drop your blood

18:07pressure based upon the equation that we

18:09just talked about here mama

18:12that's one way the other one is the

18:14venous smooth muscle I can inhibit this

18:16one so I can inhibit this one from

18:17Contracting and I can inhibit this one

18:18from Contracting so I'm going to block

18:20my nephron epinephrine binding here and

18:22that's going to cause this one too same

18:23thing it's going to relax

18:25this is going to Vino dilate but here's

18:28where it's different when veins dilate

18:30these are supposed to now naturally

18:32think about whether they do any squeeze

18:34when they squeeze they pump blood up

18:36into the right heart

18:39which improves preload the amount of

18:41volume that's coming to the right heart

18:42or the heart in general during diastol

18:44during diastole

18:46if I relax it what happens to my my

18:49preload I drop it if I drop my preload

18:54I'll subsequently drop my cardiac output

18:58and if I drop my cardiac output I'll

19:00drop my blood pressure oh man so alpha

19:03blockers have the ability to drop your

19:06systemic vascular resistance which can

19:07drop your arterial blood pressure and

19:09Vino dilate which will reduce the

19:10preload to the heart and reduce the

19:12stroke volume cardiac output and drop

19:13the blood pressure what are some names

19:15of these particular drugs alpha blockers

19:18so here's the thing with alpha blockers

19:20there's actually two types there is

19:22selective selective

19:25and then there is uh let's call these

19:29non-selective

19:31selective now with the selective types

19:34selective types this is going to be

19:36those ones that only block the alpha one

19:40they only block the alpha-1 receptor

19:42non-selective means it could buy it

19:45could actually inhibit the Alpha One and

19:47the alpha two receptors

19:49okay The Selective ones are going to be

19:52things like prizes in

19:55terrazasin

19:58doxazosin

20:02things of that nature they usually end

20:04in the zosin okay

20:07there's also tamsulosin as well but

20:08these are particular drugs that we can

20:10give now here's what I want you to think

20:12about

20:13when you give these particular drugs

20:16that really dilate the arteries okay

20:18they dilate the arteries when you dilate

20:21the arteries what's it going to do to

20:22your systemic vascular resistance we

20:23already talked about this we said that

20:24when you dilate you reduce the systemic

20:27vascular resistance now what's really

20:29interesting about this is when you drop

20:31BP there's a there's kind of like a

20:34natural reflex do you guys know that

20:35that whenever you actually have a drop

20:37in blood pressure what this does is that

20:40stimulates your baroreceptors that goes

20:43and sends the signals to your medulla

20:45your central nervous system says hey hey

20:48BP is low we got to increase that heart

20:50rate and it sends an increased

20:52sympathetic outflow which increases your

20:54heart rate what is that called that's

20:57called reflex tachycardia so these

20:59patients who have arterial vasodilators

21:02watch out for what's called reflex

21:05tachycardia

21:07as a response to dilating the arteries

21:09and then reducing resistance reducing

21:11blood pressure creating a reflex

21:13compensatory tachycardia

21:15the non-selective agents these are going

21:18to be interesting drugs we don't

21:20commonly utilize these I've talked about

21:22them in the adrenergic antagonist

21:25lecture but this is going to be

21:26phentolamine so phentolamine

21:30and phenoxybenzamine

21:32if you guys remember we briefly talked

21:36about these the true indications of why

21:38you would really give these is if a

21:40patient has a hypertensive crisis so if

21:43they have a hypertensive crisis

21:45and it's really secondary to something

21:47like what's called a theochromocytoma or

21:50it's due to a monoamine oxidases that

21:54are in monominoxidase Inhibitors plus

21:56they're taking like tyramine from like

21:57cheese or wine you guys know all that

21:59stuff we we could potentially utilize

22:02these drugs to be able to treat that

22:04process however there is other drugs

22:06that you can utilize in those situations

22:08but that's the big things to think about

22:10with your Alpha blocker so so far we

22:12have centrally acting clonidine Alpha

22:14methyl dopa okay

22:16we have beta blockers cardio selective

22:18they primarily inhibit the beta 1 okay

22:20and that's going to be these particular

22:22drugs here and then we talked about the

22:24alpha blockers now one more thing one

22:27more thing

22:28when you actually dilate veins here's

22:30another potential complication so one

22:32potential adverse effect here is reflex

22:34tachycardia from dilating the arteries

22:36but what if you dilate veins when you

22:38dilate veins here's another interesting

22:40thing when you dilate veins

22:43another thing is that you reduce

22:46your preload

22:48okay when you Vino dilate

22:50when you reduce preload you reduce

22:52stroke volume cardiac output and reduced

22:54blood pressure

22:55what's interesting about this is that if

22:58a patient who is very preload dependent

23:01an older individual who goes from a

23:04seated position to a standing position

23:05or goes from a supine to a seated

23:07position when they move they

23:09automatically have a fluid shift where

23:11blood should increase and go back to the

23:13right heart improve their preload their

23:15cardiac output their blood pressure

23:17but if those patients who you just took

23:19away their preload dependency because

23:21you Vino dilated them now when they go

23:24to get up they have no blood coming to

23:26their right heart because you dilated

23:28them you reduce their venous return so

23:30you drop their cardiac output and you

23:32drop their blood pressure and they

23:33develop oh orthostatic hypotension so

23:37watch out for that for the Vino dilation

23:39effect so this would be from the Vino

23:41dilation effect where you can cause

23:42ortho

23:44stasis beautiful okay

23:48you thought we were done or not there's

23:50one more

23:51one more category here that's really

23:54interesting here

23:55this one we're going to sneak here in

23:56the middle and this fourth category

23:58Believe It or Not we've already

24:00discussed

24:01and this is a mix blocker this is a

24:04mixed blocker so these are alpha and

24:08beta blockers so they have the

24:12capabilities of blocking the alpha

24:13receptors in the arteries and veins

24:15they also have the ability to block the

24:18beta receptors on the nodal cells in the

24:20contractile cells so they have all of

24:22the similar types of effects they may

24:25have these potential adverse effects

24:27they may have these potential adverse

24:29effects generally not the reflex

24:30tachycardia why because they suppress

24:33the actual heart rate so generally you

24:36may see bradycardia not as common to see

24:38The Reflex tachycardia from these two

24:40agents all right so there's two

24:43particular agents here for the alpha

24:44blockers and beta blockers one is called

24:46labetalol

24:48and the other one is a really

24:49interesting drug called Carvedilol

24:52these are two particular agents that we

24:54can give and again you're going to see

24:56all the same similar side effect profile

24:58more particularly the bradycardia you

25:00can see hypotension right because it can

25:02really drop the patient's blood pressure

25:03because like a vasodilate and beta block

25:05and it can cause hypoglycemia and

25:07awareness on top of that it may cause a

25:09little bit of orthostasis but there's

25:10one more thing

25:12these they can bind to beta 1 and beta

25:152. so because they combine onto beta 2

25:17guess what's a potential adverse effect

25:19my friends it can bind onto the beta 2

25:23receptors and the bronchials on the

25:25bronchial smooth muscle and when it

25:27binds onto the beta 2 receptors and the

25:29bronchial smooth muscle guess what it

25:31can do

25:32it can cause bronchospasm so there's

25:34beta 2 receptors and labetal on

25:36Carvedilol don't mind that binding that

25:37one and if you stimulate that one you

25:39will cause

25:42Bronco

25:43spasm sorry so generally sorry beta2

25:46receptors if you stimulate them they'll

25:48actually bronchodilate but these are

25:49beta blockers so they'll inhibit the

25:52beta-2 receptor and if you inhibit the

25:54beta-2 receptor you lose the ability to

25:55bronchodilate and therefore cause

25:57bronchospasm so this may be another

26:00adverse effect that you would see from

26:02Carvedilol or labetalol not as much so

26:05from metoprolol asthma lobosoprolol or

26:07Atenolol okay we've talked about

26:09sympathalytics a lot so far let's come

26:12down talk about diuretics and how they

26:15also are utilizing hypertension what are

26:17those drugs and some adverse effects all

26:19right so next category diuretics now

26:21diuretics are really interesting and why

26:22would we use it you're probably exactly

26:24why would I use it for hypertension

26:25we'll talk about why we would use them

26:27but there is three particular categories

26:29of diuretics now the whole basic concept

26:31of why we would use diuretics in the

26:33treatment of patients with hypertension

26:35is relatively straightforward

26:37and the concept of it is is that when

26:39you give a particular diuretic what a

26:40diuretic is doing is it's inhibiting

26:43sodium and water retention so it's

26:45really inhibiting the kidneys from being

26:47able to retain any sodium and water so

26:49any of the sodium there's going to be

26:50less sodium and then subsequently less

26:52water now you're probably like okay why

26:54is that potentially beneficial well now

26:56that I actually went and I peed out

26:59a lot of this sodium and water so now I

27:01peed out lots of sodium

27:03I peed out lots of water lots of this is

27:06in my urine now I'm going to effectively

27:09decrease the amount of sodium and water

27:10within my bloodstream what is that

27:12equivalent to that's equivalent to blood

27:14volume so now by giving a diuretic I'm

27:17going to decrease my blood volume

27:20if I decrease blood volume I decrease

27:22the amount of blood that is able to be

27:24returned to the right heart therefore I

27:28reduce preload

27:29because I'm reducing my venous return

27:32if I reduce preload I reduce stroke

27:34volume and cardiac output and I have

27:35reduced stroke volume cardiac output I

27:37reduce blood pressure

27:39and so you see why this may be

27:41potentially beneficial

27:43and really the only situations where it

27:46would be beneficial is if the blood

27:47volume is like really high and what kind

27:49of conditions would blood volume be high

27:51that actually you may benefit from

27:54pulling some of that sodium and water

27:55off really volume overload States and so

27:59you may find that the true indication of

28:02giving these particular drugs these

28:03diuretics may be beneficial in patients

28:05who are volume overloaded so it may be

28:07indicated in a patient who has some type

28:09of congestive heart failure or they have

28:12volume overload which is iatrogenic so

28:14maybe they've been in the hospital for

28:17like you know a couple days and they've

28:18gotten like crushed with 20 liters of

28:20fluid in that situations these may be

28:23particular drugs that we could give to

28:25pull some of the sodium pull some of the

28:27water out of the actual blood and then

28:30reducing blood volume reducing preload

28:32cardiac output and lowering blood

28:33pressure again we'll go over some more

28:35indications later but I just want you to

28:37get the basic concept of why that could

28:38potentially be beneficial now the basic

28:40mechanism of action we're going to cover

28:42we're not going to go into detail

28:43because we're over that in the diuretics

28:44lecture but the basic concept here is

28:47that when you give a diuretic there's

28:49three particular diuretics one category

28:51here we're going to put this one here

28:53first one category is called your

28:55thiazide diuretics so here's one

28:57category first first one is your

28:59thiazides now thiazides there's a couple

29:02different drugs and we'll talk about

29:03them but what here's the basic concept

29:05when you filter fluid across your

29:07glomerulus it should move down through

29:11this part the descending limb of loop of

29:13Henley then up the ascending limb with

29:15Loop of Henley and then it gets What's

29:16called the distal convoluted tubule so

29:18right here when fluid is passing through

29:21the distal convoluted tubule there's

29:23particular channels here that reabsorb

29:25sodium and reabsorb chloride so they

29:28work to potentially pull sodium

29:31and then subsequently it'll pull water

29:34into the bloodstream when I give

29:37thiazides what thiazides are going to do

29:39is they're going to inhibit these

29:41channels

29:42and now me being able to bring sodium

29:45into the bloodstream is reduced and then

29:47subsequently the pool of water is

29:49reduced and then what happens I pee out

29:52tons of sodium chloride and water

29:56and that's the whole concept here is

29:58that I'm reducing the sodium in water

30:00which will subsequently reduce the blood

30:01volume the preload the stroke volume the

30:03cardiac output and the blood pressure

30:04what are these drugs

30:07these are hydrochlorothiazide

30:11there's also chlorothiazide

30:15there's chlorthalidone chlorthalidone

30:18and another one that's a really

30:20interesting one is called metolazone

30:23so these are the drugs that we could

30:25consider thiazides

30:27now they're really good at hypertension

30:29and believe it or not they happen to be

30:31one of the first line agents for

30:33hypertension and that's a really cool

30:34concept here they're actually really

30:36really good and uncomplicated essential

30:39hypertension and any kind of category

30:41where the patient be uh you know

30:43generally younger and have really no

30:46other particular problems it's a pretty

30:48good drug if they have CHF it actually

30:50can provide an extra benefit as well are

30:53another drug category is another

30:54interesting one it works here so we have

30:56the distal convoluted tubule via the

30:57thiazides the other one over here the

31:00second category of drug

31:02is another one that we can utilize and

31:04this is called a Loop Diuretics so these

31:06are your Loop Diuretics now the Loop

31:09Diuretics there's a couple of these but

31:11what they do is here at the ascending

31:13limb so here's the fluid it's running

31:14through the ascending limit of the loop

31:16of handling generally there's a sodium

31:17potassium two chloricotransport that

31:20pulls massive amounts of sodium and pull

31:23massive amounts of water across the

31:25kidney tubules and into the bloodstream

31:27well if I give a loop diuretic what it's

31:29going to do is it's going to inhibit the

31:31sodium chloride sodium potassium to

31:34chlorideco transporter and I inhibit the

31:36sodium and water reabsorption I drop the

31:38blood volume the preload the stroke

31:39volume cardiac output and the blood

31:40pressure

31:42what kind of drugs are there here these

31:44could be Furosemide

31:46furosemide this would be bumetanide

31:51this would be torsomide

31:54these are very very commonly utilized

31:57drugs particularly in patients who have

31:58CHF now thiazides are really good for

32:01essential hypertension so it is

32:03important to remember this is going to

32:04be out of all the diuretics the one that

32:05we would likely use for hypertension is

32:08going to be this one this is likely

32:09going to be your first line agent out of

32:11all of that diuretics you really won't

32:13go to Loops the loops are mainly going

32:15to be patients through or like

32:16completely informantly volume overloaded

32:19and have CHF and you're giving it more

32:21for the symptom control you're trying to

32:23treat their hypertension but they're so

32:24volume overly you pull that volume off

32:25you'll pull their blood pressure down

32:27that's really the true only indication

32:28for loops now these drugs have similar

32:32side effect profiles again we'll go over

32:33them in the actual diuretics lecture but

32:35for right now since they pull lots of

32:37sodium since they pull chloride into the

32:40actual urine what would you see as a

32:42potential adverse effect from both of

32:43these you can see hyponatremia

32:46you can also see that when you pull

32:49sodium you also pull potassium and

32:52protons and so from these drugs you can

32:54also see hypokalemia

32:57and you pull protons so you can also see

33:00metabolic

33:02alkalosis as another potential adverse

33:06effect so you can also see metabolic

33:09alkalosis

33:11the other thing here which I'll talk

33:13about briefly

33:14is that they both inhibit uric acid

33:18excretion of the proximal convoluted

33:19tubule and so because of that they can

33:22really bump up your uric acid levels and

33:24so you want to watch out for this don't

33:26give this to people who got a big old

33:27hot big toe from gout okay because this

33:31can really bump up your uric acid levels

33:33Loop Diuretics Also may jack up the ear

33:35too so watch out for ototoxicity but

33:37again we'll go over all of these in more

33:38detail in the diuretic lecture

33:40all right the last category here of

33:42diuretics is the third one here and this

33:44is an interesting one so this is called

33:46aldosterone antagonist so you're

33:49probably like wait aldosterone I thought

33:50exactly we were going to talk about

33:51aldosterone and the Renaissance

33:53aldosterone symptoms Inhibitors we will

33:55but this one also acts as a diuretic so

33:57let's talk about it

33:59so this one is your aldosterone

34:01antagonist now this one does have

34:03diuretic capabilities but it's really

34:05important to remember that it is

34:06extremely mild so it's not a super great

34:08diuretic but what they're going to do is

34:11at the same point of the distal

34:12convoluted tubule there's also receptors

34:16okay there's receptors that from

34:18aldosterone so aldosterone has the

34:20ability to act on intracellular

34:21receptors that are present in these

34:23distal convoluted tubular cells

34:25it's actually just draw it right here

34:27here we're going to say that this is a

34:28distal convoluted tubule cell right here

34:31is these

34:33channels here sodium chloride channels

34:36aldosterone antagonists will actually

34:38work here's aldosterone it'll bind onto

34:40a receptor and that'll actually activate

34:43particular enzymes that'll synthesize

34:45these particular channels that pull what

34:47sodium

34:49and pull water

34:52into the bloodstream if I give a drug

34:55like an aldosterone antagonist what

34:56it'll do is it'll inhibit aldosterone

34:59from being able to bind onto the

35:00receptor inhibit the synthesis of these

35:02Transporters and inhibit sodium and

35:04water reabsorption dropping blood volume

35:06dropping cardiac output dropping blood

35:08pressure

35:09now these drugs are going to be things

35:12like

35:13apler known

35:16and this is also going to be things like

35:18amyleride

35:20and another one called spironolactone

35:25and these drugs again not super powerful

35:28hypertensive agents but they can be

35:31utilized to reduce mortality in patients

35:33with CHF one of the big things to watch

35:36out for with these drugs and we'll

35:37probably recap it a little bit later is

35:39that because they inhibit aldosterone

35:40industria not only reabsorbs sodium and

35:42water it excretes potassium so you

35:45inhibited the excretion of potassium so

35:47potassium can actually go up it's the

35:49only one that actually spares potassium

35:51so watch out for hyperkalemia with this

35:54particular drug and then with

35:55spironolactone it can actually cause the

35:58blockage of multiple other androgens so

36:02sex hormones and so this may lead to the

36:05effect of gyneco mastia so watch out for

36:10gynecomastia with spirano

36:13lactone all right my friends that covers

36:16the diuretics

36:18so we've covered this in patholytics

36:19we've covered the diuretics now let's

36:21move on to the next category which is

36:23the rain and Angiotensin aldosterone

36:25synthesis Inhibitors all right so renin

36:27Angiotensin aldosterone synthesis

36:28Inhibitors man it's a mouthful with

36:30these particular drugs how do they work

36:32to treat hypertension well we've got to

36:34briefly go through the pathway all right

36:36kidneys they make a very special

36:38molecule called renin now your question

36:41that should be popping out there is well

36:44what actually triggers random production

36:45Zach ah great question so on the actual

36:48kidney there is special receptors called

36:50beta 1 receptors right so there is beta

36:521 receptors that are present on these

36:54cells in the kidney called the

36:55juxtaglomerular cells and when

36:57stimulated stimulated by what

36:59the sympathetic nervous system so the

37:01sympathetic nervous system can release

37:02what type of molecule here noro

37:04epinephrine that'll act on these beta-1

37:06receptors and start pumping out renin

37:08that's one particular mechanism the

37:10second mechanism that actually causes

37:13random production here

37:14is that whenever a patient has low renal

37:16perfusion so if there is a very poor

37:19perfusion to the kidneys so a decreased

37:22perfusion so a decreased perfusion maybe

37:24this is due to a decreased cardiac

37:26output so there's a reduced perfusion to

37:28the kidneys this can also stimulate the

37:31juxtaglomerular cells to pump out renin

37:34but either way renin is being made

37:36when Raiden is made and it's made in a

37:38lot it interacts with a very special

37:41molecule made by the liver what is this

37:43molecule called This is called angio

37:46tensinogen

37:50now Andrew tensinogen is made by the

37:52liver what happens is renin when it's

37:55made it acts on angiotensinogen and what

37:58it does it actually takes

37:59angiotensinogen and converts it it

38:01stimulates this it runs an enzyme and it

38:04stimulates angiotensinogen by cleaving

38:05off a couple amino acids and turns it

38:07into something called Angiotensin one

38:10now Angiotensin 1 then goes to the lungs

38:13in the capillary endothelium of the

38:15lungs there is this special cool enzyme

38:18what is this enzyme this enzyme is

38:21called angio tension converting enzyme

38:26this enzyme is a very powerful enzyme

38:29and what it does is it takes Angiotensin

38:31one Cleaves off a couple more amino

38:33acids and then synthesizes something

38:36called angio

38:37tencent II

38:40so let's actually do it like this let's

38:41actually say here's Angiotensin one

38:43it'll run through here and it'll pop out

38:45here after it interacts with this enzyme

38:46into Angiotensin II which is in the

38:49lungs

38:49now what happens here

38:52Angiotensin II then goes and acts on

38:54varies different tissues various

38:57different tissues one is it can go over

38:59and act on the heart tissue it can also

39:02come here and act on the adrenal cortex

39:04it can also come here and act on the

39:06central nervous system it can also come

39:09down here and we'll talk about this a

39:10little bit later I'm just going to draw

39:11a couple dotted lines but it has the

39:13ability to come down here and work on

39:14special parts of the kidney tubules as

39:16well and exert many different effects

39:18that can work to increase the patient's

39:20blood pressure let's talk about that all

39:22right so now Angiotensin II is made

39:24right it's synthesized okay once

39:27Angiotensin II is made it then goes and

39:28it works on blood vessels and it's

39:30really powerful very very powerful so

39:33here is the artery right here's an

39:35artery of our coronary of our vascular

39:38systemic circulation and here's the vein

39:40now normally again the artery if we take

39:43a piece of a cell here and actually zoom

39:44in on we're going to see this piece of a

39:46cell here we're going to zoom in on so

39:47here's a arterial smooth muscle cell and

39:49here's a venous smooth muscle cell on

39:51these they have a very special type of

39:53receptor this is called an angio

39:56tensin II receptor so this is an

40:00Angiotensin II receptor

40:03when Angiotensin II binds onto this

40:06particular receptor it produces a very

40:08profound load of ions positive ions into

40:12these actual smooth muscle cells which

40:13causes an intense contraction and when

40:16it causes this intense contraction of

40:18the actual smooth muscle cells it does

40:19what well naturally it'll cause the vein

40:22to squeeze like a son of a gun so here

40:24we're gonna have two Pathways here this

40:25is going to be the normal pathway by

40:27Angiotensin so for the arterial pathway

40:30this is the normal pathway when

40:32Angiotensin II is high it'll actually

40:34cause

40:35vasoconstriction so if it causes Vaso

40:38constriction it'll really cause the

40:42blood vessel the actual blood vessel

40:43diameter to decrease and that really

40:45pumps up your systemic vascular

40:47resistance and that really pumps up your

40:49blood pressure so your blood pressure

40:50goes up intensely

40:52on top of that it also works on the

40:54venous smooth muscle cells and when it

40:56works on them it actually causes Vino

40:58constriction

41:00and if you these venal constrict these

41:02poppies you're going to really push a

41:04lot of blood where into the right heart

41:07and so it increases your preload

41:10and if you increase preload you increase

41:12stroke volume cardiac output and

41:14subsequently you increase blood pressure

41:16so that's one way that Angiotensin II

41:18can directly increase our blood pressure

41:20is by squeezing the heck out of the

41:22arteries and squeezing the heck out of

41:23the veins increasing resistance

41:25increasing preload and subsequently

41:27increasing blood pressure

41:29okay

41:30another thing Angiotensin II can do is

41:32it can act on the adrenal cortex

41:34and the adrenal cortex will then start

41:36pumping out a very special type of

41:38molecule this molecule is called

41:41aldosterone you're probably wondering

41:42where did the aldosterone come from

41:44before when aldosterone is actually

41:46synthesized it's synthesized because

41:48Angiotensin II is stimulating the

41:49adrenal cortex to pump it out so now

41:51it's going to be stimulated here

41:53aldosterone will then work its way down

41:55to the actual kidney tubules and when it

41:58gets into the kidney tube is what it

41:59does is remember I told you it acts on

42:01specialist receptors that increase

42:03sodium and chloride Transporters on the

42:05tubular Lumen and because of that you

42:08can pull more sodium and water into the

42:10bloodstream so the effect here is that

42:11you're going to yank more sodium and

42:14more water into the bloodstream so the

42:16effective process here is of increased

42:18sodium it'll increase water and that

42:21will do what that'll increase your blood

42:24volume and we know that if we increase

42:25blood volume we increase preload we

42:27increase stroke volume cardiac output

42:28blood pressure yada yada

42:30that's one effect

42:32okay it also we'll talk about this

42:35little effect here later that we're

42:36gonna actually let's just do it now

42:38let's just do it now here I'll dot

42:39Angiotensin 2 can also come over here

42:41now it does work here again to stimulate

42:45the zone glomerulosa to make aldosterone

42:46increase sodium water reabsorption

42:48increase blood volume but it also can

42:50act over here

42:51on the arterial system so you know blood

42:54going into the glomerulus this is your

42:56afferent arterial so this artery here

42:58and then leaving the glomerulus this

43:00part here is your efferent arterial

43:02there's lots and lots of Angiotensin II

43:05receptors that are present on the

43:06efferent arterial and you're probably

43:08wondering like why all right all right

43:10well I got you

43:11so here on the efferent interior there's

43:13a lot of Angiotensin II receptors when

43:15Angiotensin II binds on to these

43:18receptors and efferent arterial it

43:20squeezes the heck out of them

43:23if you squeeze so imagine here I'm going

43:26to squeeze on this efferent arterial

43:29what do you think is going to happen if

43:31I have Angiotensin 2 here

43:34and I squeeze I bind onto these efferent

43:37arterial receptors I squeeze them I

43:40vasoconstrictor what's going to happen

43:42to the pressure so imagine you have like

43:44I'm squeezing here and blood is supposed

43:46to be leaving the glomerulus and going

43:48into the affair materials now it's being

43:50occluded the pressure in the glomerulus

43:52is going to shoot up because of that if

43:56I stimulate this thing if I

43:57vasoconstricted guess what's going to

43:59happen

44:00I'm going to increase the glomerular

44:02blood pressure

44:04if I increase the glomerular blood

44:05pressure I'm going to subsequently

44:07increase the glomerular filtration rate

44:09I'm going to increase protein to be lost

44:13protein loss and I'm going to thicken

44:17the glomerular basement membrane these

44:19are the three problematic issues with

44:21this because if the pressure in the

44:22glomerulus is super super high it's

44:25going to cause you to now push tons of

44:26fluid which is going to be fluid and

44:29proteins into the actual convoluted

44:31tubular system so that's going to cause

44:32a massive GFR massive protein loss but

44:35it's also going to put a lot of injury

44:37on the glomerular base membrane from

44:38high pressure and it can thicken it and

44:40progress patients to chronic kidney

44:42disease

44:43oh man it's the son of a gun that's

44:46Andrew turns into

44:48okay so one thing is it squeezes

44:49arteries veins it then increases

44:52aldosterone which increases sodium water

44:53reabsorption it causes efferent arterial

44:55vasoconstriction which increases

44:57interglomerular blood pressure increases

44:59GFR increases protein loss and thickens

45:01the glomerular basement membrane what

45:03else can this son of a gun do don't

45:04worry there's more it also tells the

45:06posterior pituitary to pump out what's

45:09called antideretic hormone antideretic

45:12hormone will then work its way down to

45:14the actual kidney tubules at the

45:15collecting duct so here's the collecting

45:16duct this one worked here aldashin at

45:18the distal convo to tubule but what ADH

45:21does is it actually works on aquaporins

45:23it increases the expression of

45:24aquaporins which pulls and Yanks water

45:26into the bloodstream so it increases

45:30water reabsorption and if you increase

45:32watery absorption you increase blood

45:34volume now again we're seeing an effect

45:37of an increase in blood volume so with

45:39the combination of aldosterone and ADH

45:42what you're seeing here is with ADH

45:46and with

45:48aldosterone is you're seeing a really

45:50interesting combo here you're seeing

45:53that they're working on the kidneys to

45:56retain sodium and water and so because

45:58of that they're going to do what they're

46:00going to pull more sodium and water into

46:02the bloodstream that's going to increase

46:04sodium water reabsorption that'll

46:07increase blood volume that'll increase

46:10preload

46:12that'll increase stroke volume and

46:15cardiac output and that'll increase the

46:17patient's blood pressure you're like

46:19Zach okay I thought that we were

46:20supposed to talk about antihypertensives

46:22in this dang lecture we are but now we

46:24know exactly how these antihypertensives

46:27are going to work now for this system

46:28let's come up let's talk about the drug

46:31categories because there's three of them

46:32that I want to go through first one is

46:34going to be starting here at the ace

46:35then we'll come down here and talk about

46:37the Angiotensin II receptors and then

46:39we'll finish off with aldosterone

46:40antagonists briefly recapping because we

46:42already talked about it all right so the

46:43first category of drugs now there is one

46:45drug up here that you technically do

46:47have a drug that it can inhibit renin

46:48it's called Alice Chiron but it's just

46:50not utilized we don't utilize you

46:52theoretically it seems like an amazing

46:53drug but we just don't use it so Alice

46:55Chiron is one of those drugs but I'm not

46:56even going to write it down because

46:57again it's not a drug that you're really

46:58ever going to see or prescribe

47:00a drug that you will see and will

47:02prescribe is ACE inhibitors okay so

47:04these are very commonly utilized drugs

47:06so ACE inhibitors is going to be one of

47:09these types of drugs in the renin

47:11Angiotensin aldosterone blockers so what

47:13is this drug category here

47:15this is going to be your ACE inhibitors

47:18your Angiotensin converting enzyme

47:20Inhibitors these are really really good

47:22drugs I really like these drugs and one

47:25of it sounds a little weird when I say I

47:26really like drugs but this drug here is

47:28you remember the prills all right so

47:30this is like Lisinopril

47:32this is a really commonly utilized one I

47:34actually common I prefer captopril as

47:37well this is a really good one

47:39um there's also um another one called

47:41benzopril

47:44um and then there is also enalapril

47:47there's a lot of these men out there so

47:50there's a lot of different just remember

47:51the prills okay

47:53now with these particular drugs you're

47:55wondering how do they actually help with

47:57hypertension right okay what they do is

47:59these drugs these ACE inhibitors they're

48:02inhibiting the ace enzyme if they

48:04inhibit the ace enzyme they inhibit

48:07Angiotensin 1 being converted into

48:09Angiotensin II so they subsequently drop

48:12the angiotensin two levels if I drop the

48:15angiotensin two levels my friends tell

48:17me tell me please what is the overall

48:20effect of this the overall effect of

48:23reducing Angiotensin II is that I'm

48:26going to

48:28reduce

48:30arterial

48:32vasoconstriction

48:34I'm going to reduce Vino

48:37constriction

48:39I'm going to reduce aldosterone

48:42oh my gosh there's so many things I'm

48:44going to reduce ADH production I'm going

48:48to reduce the glomerular blood pressure

48:50all of these things are going to be

48:52helpful

48:53so I'm going to reduce the patient's

48:55arterial vasoconstriction that's going

48:57to reduce the resistance reduce their

48:58blood pressure I'm going to reduce Vino

49:00constriction that's going to reduce

49:01preload reduce stroke volume critical

49:02blood pressure I'm going to reduce our

49:04Dash from reduce sodium water

49:06uh ADH reduced water reabsorption reduce

49:09blood volume preload stroke volume

49:10cardiac output and I'm going to reduce

49:11the glomerular blood pressure preventing

49:13GBM thickening preventing protein urea

49:15preventing an increase in GFR now that

49:18may be interesting right we'll talk

49:19about that a little bit why would you

49:20want to drop the GFR that's one of the

49:22potential downsides that you can

49:23actually see or an adverse effect of

49:25these drugs we'll get to it a little bit

49:26later

49:27one big thing with these drugs okay is

49:31aces not only convert Angiotensin 1 to

49:33angiotensin two

49:35let's see let's do this in this

49:38beautiful color here okay there's a

49:40molecule called bradykinins

49:43Brady kindness now bradykinins are these

49:47very interesting like little molecules

49:48kind of like little inflammatory

49:50mediators if you will

49:52and they're supposed to be acted on by

49:54the Angiotensin converting enzyme into

49:56like these different inactive

49:57metabolites that don't have that type of

50:00inflammatory nature to them if I give an

50:03Ace inhibitor

50:04I inhibit the conversion of bradykine

50:06into the inactive metabolites

50:08and so what happens to the bradykinin

50:09levels they go up

50:11if bradykinin levels go up the problem

50:14with this is two potential things one

50:18is that elevated levels of bradykinin

50:20can actually cause

50:22agitation of cough receptors and so this

50:25will cause patients to have a nasty low

50:27cough

50:28it also can cause an increase in

50:31inflammation so it can cause a little

50:32bit of vasodilation of the pulmonary

50:34blood vessels or the bronchial blood

50:35vessels and cause capillary leakage so

50:38it may cause inflammation particularly

50:40if some of the upper respiratory tree

50:42and low respiratory tree so this may

50:43cause angioedema

50:46so watch out for these things which

50:48you're going to see way more commonly

50:50with ACE inhibitors than you will with

50:52the other drugs within this category so

50:54there's a lot higher risk of dry cough

50:55and angioedema due to alternating

50:58altering the bradykinin pathway all

51:01right beautiful okay

51:04the next drug category is the

51:06aldosterone and I'm sorry the

51:08Angiotensin II blockers or the

51:11Angiotensin II receptor blockers so

51:14let's talk about this drug category here

51:17so the second drug category that I want

51:19to mention here the second drug category

51:23and I often find me I am very fond of

51:25these ones as well is your angio

51:28tencent to receptor blockers your arbs

51:33your arbs

51:34these drugs there's a lot of these

51:37lazartan

51:39Valsartan

51:42candazartan

51:44lots of these particular medications

51:47but the basic concept here is that these

51:50drugs Angiotensin II receptor blockers

51:53will bind onto all of the receptors that

51:56Angiotensin II binds onto so everywhere

51:59that Angiotensin II receptors are going

52:01to bind everywhere Angiotensin II binds

52:03onto a particular receptor it's going to

52:05inhibit it so what would that do let's

52:07come down and take a look at what that

52:08would do so what would it do think about

52:09it Angiotensin II binds onto the

52:11Angiotensin II receptors on the venous

52:12smooth muscle and the arterial smooth

52:14muscle smooth muscle so it's going to

52:16inhibit it on these two particular sites

52:19so what's that going to look like it's

52:20going to inhibit venal constriction and

52:22it's going to inhibit arteriolar

52:24vasoconstriction so it's going to again

52:25inhibit Angiotensin

52:28angiotensin two blocking and so that

52:31will again reduce arterial

52:35arterial

52:37vasoconstriction

52:39that'll reduce systemic vascular

52:40resistance it'll reduce Vino

52:42constriction that'll reduce preload

52:44that'll reduce your cardiac output your

52:46blood pressure what else

52:48it also will inhibit the aldosterone

52:51release so it'll block these particular

52:53receptors and it'll block ADH from being

52:55able to be released so it'll reduce

52:58ADH it'll reduce aldosterone what's the

53:02overall effect of these two particular

53:04things if you inhibit aldosterone you

53:06inhibit sodium and water reabsorption if

53:08you inhibit ADH you inhibit water

53:10reabsorption this inhibits the increase

53:12in blood volume this inhibits the

53:14increase in preload stroke volume critic

53:15output and what else

53:18you also inhibit Angiotensin II from

53:20being able to bind onto the

53:22Angiotensin II receptors on the efferent

53:24arterial that's going to lower the

53:26glomerular blood pressure that'll then

53:28reduce the GFR reduce the protein loss

53:31and reduce the thickening of the

53:32glomerular basement membrane

53:34man we could

53:36now angiotensin two receptor blockers

53:39and ACE inhibitors are very commonly

53:41utilized drugs

53:42Okay the reason that you also want to

53:45think about these drugs is really

53:46because

53:48because they have the ability to inhibit

53:50aldosterone right they reduce

53:52aldosterone production what is a

53:54potential adverse effect that you may

53:56see from both the Angiotensin receptor

53:58blockers and the ACE inhibitors so

54:00because of inhibits aldosterone you

54:03actually can see hyperkalemia so watch

54:05out for hyperkalemia because it reduces

54:08the glomerular blood pressure it's going

54:10to reduce the GFR

54:12so if it reduces the GFR

54:15it can actually do what to the

54:17creatinine it can decrease your

54:19creatinine clearance and so the

54:20creatinine can actually increase so

54:22watch for that as well

54:24and the other thing is these are

54:25teratogenic so don't give this to a

54:27pregnant woman as well so these are some

54:29of the things that you want to be able

54:30to consider with these particular drugs

54:32so Angiotensin receptor blockers they

54:34may bump the potassium they may increase

54:37the creatinine by dropping the GFR

54:40but again I think the other thing is

54:41that you get more of a cough a dry cough

54:43from the bradykinins and angioedema more

54:46particularly from the ACE inhibitors ACE

54:48inhibitors can also cause hyperkalemia

54:50and drop your GFR and again increase

54:54your creatinine so you can see both of

54:55these effects and both of these

54:58particular drug categories okay but you

55:00see more of the angioedema and more of

55:01the dry cough in the ACE inhibitors

55:03okay the last category my friends is the

55:08Angel the aldosterone antagonist and

55:10thankfully we've already covered these

55:12but just to recap them again aldosterone

55:17antagonists

55:19is the third category within this drug

55:22situation here and this is again your

55:24Epler known

55:27this is your

55:28spironolactone

55:32and this is your amyloride

55:36and again remember with these that

55:38you're inhibiting aldosterone so because

55:39you're inhibiting aldosterone you have

55:41the ability to cause hyperkalemia so

55:43watch out for hyperkalemia

55:46and again because spironolactone

55:48um blocks the androgens so a lot of

55:51steroid hormones that are involved

55:52within a lot of you know sex drive and a

55:54lot of other things this can potentially

55:56lead to one adverse effect that you see

55:58called gyneco mastia more particularly

56:01with this drug

56:03but that is the concept of these ACE

56:05inhibitors in these arbs is that they're

56:08really really good at being able to

56:10treat blood pressure and really reducing

56:12your blood pressure through all of these

56:14mechanisms that we went through where is

56:16the aldosterone antagonist they're

56:18really only going to be doing what

56:19they're really only going to be reducing

56:21sodium and water retention so that may

56:24be a benefit if potentially more for the

56:26diuretic type of function but you'll see

56:27later that this is a drug that has been

56:29shown to be potentially beneficial and

56:31reduce mortality so it may be a drug

56:33that we give to patients who have CHF

56:35because it actually can provide some

56:37augmentation of diuresis but it also

56:39reduces mortality associated with that

56:41disease so we'll talk about that a

56:43little bit later but that is the whole

56:45concept of these drugs now that we've

56:47finished these off we have one more

56:49category that's our vasodilators let's

56:51hop over there all right so now we're

56:52going to talk about the last class of

56:54drugs which are our vasodilators okay

56:56now vasodilating is very interesting

56:58right so let's talk about how

57:00vasodilation occurs really and what's

57:02the overall effect fact if it was in an

57:04artery

57:05versus if it was like in a systemic vein

57:08so if I were to do this let's just do

57:11the arterial proportion first here in

57:13Red so if an artery right is working to

57:16control blood pressure if I have an

57:18artery

57:20right and it undergoes vasoconstriction

57:22right so it squeezes right so it

57:25squeezes and when it squeezes it

57:27undergoes Vaso

57:29constriction what will happen is that

57:32will cause an increase in systemic

57:34vascular resistance and subsequently an

57:36increase in your blood pressure we know

57:38that okay

57:40the next thing is in the vein the vein

57:42is also really important right so when

57:44the veins are potentially working and

57:47actually being acted on through specific

57:49Vaso you know mechanisms vasotone

57:51mechanisms when the veins constrict so

57:54you have what's called Vino constriction

57:56so we're going to call this Vino

57:58constriction when they constrict what

58:01they do is they help to actually

58:03increase preload so they squeeze more

58:06blood up into the right heart whereas if

58:10I squeeze these arteries I'm making a

58:12difficult more resistance to blood flow

58:15as it flows through the arterial circuit

58:17right so because of that if I increase

58:19preload I increase the amount of blood

58:21going back to the heart I increase my

58:23stroke volume my cardiac output and

58:25subsequently I increase my blood

58:26pressure

58:27so when I give drugs there's two

58:29categories of drugs

58:31one is called venodilators right so I

58:34want to talk about the drugs that are

58:36actually what's called Vino

58:38dilators

58:40and these Vino dilators what will they

58:42potentially do these Vino dilators will

58:45actually inhibit

58:47Vino constriction reduce preload reduce

58:49stroke volume reduce cardiac output and

58:51reduce blood pressure that's how they'll

58:53treat that process and then you have

58:55another category of drugs here which are

58:58called your arterial

59:00dilators

59:03and these will work by doing what

59:05inhibiting the vasoconstriction of the

59:07arteries which will and drop the

59:09systemic vascular resistance and drop

59:11the blood pressure

59:13okay the first category that I want to

59:16discuss is the arterial dilators is a

59:19really interesting one

59:21we're actually going to mention it up

59:22here

59:23and what these these particular category

59:25of drugs is this is actually a drug

59:26category which I happen to be very very

59:29fond of they are called dihydropyridine

59:32calcium channel blockers so

59:35dihydropyridine

59:38calcium channel blockers really really

59:41good powerful drugs

59:43now what these do is you obviously can

59:46tell via the name that they block

59:47calcium channels there is calcium

59:50channels that are very mildly present on

59:53the venous smooth muscle but way more

59:55powerful and way more present on the

59:57arterial smooth muscle so these are

59:59going to be more particularly arterial

1:00:01vasodilators

1:00:03now what happens is calcium is present

1:00:06on these smooth muscle cells when these

1:00:08calcium channels are open calcium floods

1:00:10in and calcium will actually interact

1:00:12and be utilized within the myofilaments

1:00:15right to be able to allow for

1:00:16contraction so we know that you know

1:00:18calcium binds onto the you know it binds

1:00:20up to the different proteins like the

1:00:21troponin change the shape of the

1:00:22tropomyosin and loss for actin myosin to

1:00:24binding boom you get the sliding

1:00:25filament theory

1:00:26if I give a drug like a dihydropyridine

1:00:29calcium channel blocker what they'll do

1:00:31is they will block the calcium from

1:00:34being able to enter if calcium isn't

1:00:36able to enter is it going to be utilized

1:00:38by the myofilaments to induce

1:00:39contraction no so it will inhibit this

1:00:41process and the smooth muscle will relax

1:00:43if it relaxes it would no longer

1:00:46vasoconstricts it vasodilates if it

1:00:48vasodilates it then this is going to

1:00:50undergo Vaso

1:00:52dilation and if it vasodilates it

1:00:54reduces the systemic vascular resistance

1:00:56if you reduce the systemic vascular

1:00:58resistance you're going to drop the

1:01:00blood pressure what are the drugs that

1:01:03we utilize in this category here

1:01:05there is

1:01:07one particular drug here which I um

1:01:09commonly utilize is called amlodipine

1:01:11amlodipine is very commonly utilized one

1:01:13another one is called nifedipine it's a

1:01:16nifedipine

1:01:17another one is called nicardipine

1:01:21nicardipine

1:01:23another one is called pneumodipine this

1:01:25is a very commonly utilized one or

1:01:27subarachnoid patients and then another

1:01:29one is called clavidipine

1:01:31so with these drugs these are some of

1:01:35the drugs that you can prescribe the

1:01:36most commonly kind of like prescribed

1:01:37outpatient ones are going to be

1:01:38amlodipine and the pedophene and the

1:01:40most commonly utilized one is generally

1:01:42in the ICU or hospital kind of setting

1:01:44or as infusions is clovidipine and a

1:01:45cardiopian very very good powerful drugs

1:01:48now generally with these drugs all right

1:01:51what I really want you to understand is

1:01:53with any arterial vasodilator what is a

1:01:57potential adverse effect that you can

1:01:59see with these drugs great question with

1:02:01an arterial dilator what you do is you

1:02:04reduce systemic vascular resistance you

1:02:07reduce blood pressure what does that do

1:02:09to again your central nervous system it

1:02:12tells the baroreceptors hey hey blood

1:02:14pressure is low so it stimulates the

1:02:17baroreceptors

1:02:20and the baroreceptors once stimulated

1:02:22activates what

1:02:23your central nervous system your central

1:02:25nervous system will then stimulate a

1:02:27increase in heart rate as a reflex

1:02:30tachycardia so watch for reflex

1:02:33tachycardia with arterial vasodilation

1:02:35we saw that with the Alpha One blockers

1:02:37that they can get reflex tachycardia

1:02:39that's a very common adverse effect with

1:02:42these types of dihydroprene custom

1:02:44genome blockers or really any arterial

1:02:46vasodilator

1:02:48because they have very minimal Vino

1:02:50dilation effects they may cause

1:02:51orthostatic hypotension so there is very

1:02:54small and I mean this very importantly

1:02:56it's is a very mild amount of calcium

1:02:59channels that are present on veins

1:03:02very very little so because of that you

1:03:05could potentially see some venodilation

1:03:07effect but it's very very mild and I

1:03:10would focus more particularly on the

1:03:11arterial vasodilation now here's the

1:03:13thing that I want you guys should be

1:03:15asking the question

1:03:16you said dihydropyridine calcium channel

1:03:18blockers like it's something special

1:03:19Zach I don't understand why you

1:03:21mentioned that the calcium channels that

1:03:24are present

1:03:25on the arterial smooth muscle and even

1:03:27on the venous smooth muscle our only

1:03:29dihydropyridine they are only

1:03:32dihydropyridine

1:03:33the other types of calcium channels that

1:03:36are present in other areas like the

1:03:38cardiac myocytes are non-dihydropyridine

1:03:42calcium channel blockers and they

1:03:43deserve a discussion here too we

1:03:44shouldn't just let them out of the

1:03:46discussion as well so

1:03:48let's talk about those drugs

1:03:50so this drug is going to be the second

1:03:52category of drugs here and these are

1:03:54called your non-dihydropyridine calcium

1:03:57channel blockers I'm going to kind of

1:03:58abbreviate nah just we'll write it so

1:04:00non

1:04:02dihydro

1:04:05pyridine

1:04:07calcium channel blockers and these are

1:04:10only present so these are the only ones

1:04:13that are present on the myocardial cells

1:04:15you do not have dihydropyridine calcium

1:04:18channels that are present on the

1:04:19myocardial cells very very important to

1:04:23remember that

1:04:24so these types of structures here the

1:04:26non-dehydripating calcium channel

1:04:27blockers there's two particular agents

1:04:29here one is called Verapamil

1:04:31Verapamil and the other one is called

1:04:34diltiazem

1:04:36deltaism

1:04:37now what's really important with these

1:04:39drugs is that they work on the calcium

1:04:41channels that are on the contractile

1:04:43myocardium and on the nodal cell so on

1:04:45the AV node SC node all those structures

1:04:46and so because of that these have

1:04:49calcium channels that allow for calcium

1:04:51to flood into them right so calcium is

1:04:52supposed to move into the contractile

1:04:54cell stimulate them you know contraction

1:04:56of the contractile cell is also supposed

1:04:58to run into the nodal cell stimulate

1:05:00this cell to generate Action potentials

1:05:02and increase conduction through the

1:05:03heart

1:05:04but when I give a non-dihydropyridine

1:05:06calcium channel blocker what I'm doing

1:05:08is I'm inhibiting these calcium channels

1:05:11I'm inhibiting calcium entry into the

1:05:14contractile cell and into the nodal cell

1:05:17and therefore I will decrease

1:05:19contractility

1:05:21if I decrease contractility of the heart

1:05:25I'm going to decrease the cardiac output

1:05:27and I'm going to subsequently decrease

1:05:29the patient's blood pressure

1:05:31the nodal cell

1:05:33I'm going to reduce the heart rate

1:05:35and therefore I'm going to reduce the

1:05:36cardiac output and I'm going to reduce

1:05:38the blood pressure so these drugs can be

1:05:41utilized and hypertension

1:05:44here's the other thing it's important to

1:05:47remember

1:05:48because these drugs do primarily work on

1:05:52the heart some of the adverse effects

1:05:54that you have to watch out for there's

1:05:55two that are super obvious here one is

1:05:58it can drop the heart rate

1:05:59and so because of that you want to watch

1:06:01out for any types of bradycardia because

1:06:03this can actually drop the patient's

1:06:05heart rate the other thing is it reduces

1:06:06contractility if a patient already has a

1:06:09poor cardiac output such as an

1:06:10decompensated heart failure you could

1:06:13potentially kill them and make them

1:06:14hypotensive put them in a cardiogenic

1:06:15shock so it can really really drop the

1:06:17blood pressure and then put the patient

1:06:20into shock especially if they have

1:06:22decompensated heart failure so avoid in

1:06:25that particular situation

1:06:27one thing that you want to remember is

1:06:29that the non-dehydroputing calcium

1:06:31channel blockers they do have a very

1:06:33mild a very mild vasodilatory effect so

1:06:37these do have a small capacity to bind

1:06:41onto the dihydropyridine calcium

1:06:43channels and inhibit them so because of

1:06:46that I want you to remember that we're

1:06:47going to put this like I don't know

1:06:48let's do it in this beautiful blue color

1:06:50here is that they have an important kind

1:06:52of a mention here is that they have a

1:06:54very small

1:06:57Vaso

1:07:00dilation

1:07:02effect

1:07:04okay and if you're really comparing

1:07:05between these Verapamil has more of a

1:07:07potent effect and deltaizam is a very

1:07:09mild vasodilatory effect

1:07:11so they do have a very small

1:07:13vasodilation effect so therefore they

1:07:15can actually do what reduced systemic

1:07:17vascular resistance and also reduce

1:07:19blood pressure so you may be able to see

1:07:21a small reduction in systemic vascular

1:07:23resistance and subsequently a reduction

1:07:25in blood pressure but it's very very

1:07:27mild

1:07:28whereas these drugs the dihydroperating

1:07:31calcium channel blockers they have no

1:07:32effect on the cardiac myocytes so they

1:07:34have no

1:07:36effect on the

1:07:37cardiac

1:07:39myocytes

1:07:41so they will not be util they won't be

1:07:43able to reduce heart rate and reduce

1:07:45contractility but the non-dehydropening

1:07:48calcium channel blockers they have the

1:07:49ability to reduce heart rate

1:07:50contractility and very mild vasodilatory

1:07:52effect so they will be able to mildly

1:07:54reduce systemic vascular resins if you

1:07:56had to compare which one's better

1:07:57Verapamil has more of a vasodilator

1:07:59effect then diltiazine okay

1:08:02that's the big things that I want to

1:08:03remember for these drugs okay

1:08:05we talked about the calcium channel

1:08:06blockers very very good agents diagram

1:08:08calcium channel blockers happen to be

1:08:10first line one of my preferreds

1:08:12but now let's come down and talk about

1:08:14some other ones

1:08:15with these things we've talked about the

1:08:18calcium channels right how there's very

1:08:19very there's more calcium channels way

1:08:21more calcium channels present on the

1:08:23arterial smooth muscle and very little

1:08:24calcium channels that are present on the

1:08:26venous smooth muscle so calcium still

1:08:28can come in and then again interact with

1:08:30the smooth muscle in these venous cells

1:08:32so if you give a dihydropyridine calcium

1:08:33channel blocker or non-dihydropyridine

1:08:35they have a very mild inhibitory effect

1:08:37so they may cause Vino dilation and what

1:08:40we know about Vino dilation

1:08:42is that Vino dilation does what if you

1:08:45venodilate

1:08:47you reduce preload

1:08:50that reduces stroke volume cardiac

1:08:52output and that reduces blood pressure

1:08:56now

1:08:57that's the basic concept here okay

1:09:00so the other thing is there's there's

1:09:03one more arterial actually two more

1:09:05arterial dilators that I want to talk

1:09:07about

1:09:08they're really really cool to be honest

1:09:10with you so here we have let's say

1:09:14this special enzyme here on the cell

1:09:17membrane this enzyme is called guanol

1:09:19cyclase

1:09:21and what guanolaocyclase does is it

1:09:23takes a molecule called GTP converts it

1:09:26into what's called cyclic GMP and then

1:09:29cyclic GMP act on Exxon an enzyme called

1:09:31protein kinase G and what this does is

1:09:34this actually inhibits

1:09:36muscle contraction okay so generally

1:09:39this pathway would work to inhibit

1:09:42muscle contraction

1:09:44so if I had some way shape or form I

1:09:46could give particular drugs that could

1:09:49activate the guanol outside place that

1:09:51might be able to increase the cyclic GMP

1:09:53increase protein kinase G and inhibit

1:09:55the smooth muscle cells guess what there

1:09:57is particular drugs that can do that

1:09:59all right I can give one particular drug

1:10:01category here

1:10:03one I want to put here and we'll talk

1:10:05about in just a second can stimuli

1:10:07iguana allow cyclase directly

1:10:09and another one does it through another

1:10:11interesting way

1:10:12another drug category can actually do

1:10:15something else where they can increase

1:10:16nitric oxide

1:10:18and when you increase nitric oxide what

1:10:21this does is this also stimulates

1:10:23guanolocyclase

1:10:25if it stimulates guanolocyclase

1:10:28that stimulates this process to increase

1:10:30cyclic GMP that increases the

1:10:32phosphorylation of protein kinase G and

1:10:35that increases the inhibition of the

1:10:36smooth muscles and that will actually

1:10:38cause arterial visibilation reduce the

1:10:40resistance and reduce the blood pressure

1:10:42what are the drugs that actually work

1:10:45too directly stimulate guanolocyclase or

1:10:48increase nitric oxide to activate

1:10:50guanolocyclists let's come down and talk

1:10:52about those so that leads us to the

1:10:54third category here so the third

1:10:56category of drug that I'm going to talk

1:10:58about really

1:10:59interesting type of process here is

1:11:02these drugs are the ones that are going

1:11:03to increase

1:11:06cyclic GMP via stimulating guanol

1:11:10cyclase directly okay so these are

1:11:13actually referred to as what's called

1:11:14direct acting vasodilator so if you

1:11:17really want to put that down here you

1:11:18can actually call these direct acting

1:11:20vasodilators

1:11:22one particular drug within this is

1:11:24called hydralazine okay hydralazine and

1:11:28so hydralazine will work to actually

1:11:30cause again stimulation of

1:11:32guanolocyclists directly increase cyclic

1:11:34GMP increase protein kinaseg and then

1:11:36inhibit the arterial smooth muscle and

1:11:38cause it to relax that'll cause arterial

1:11:41vasodilation that'll cause decrease in

1:11:43resistance and decrease in blood

1:11:44pressure now hydralazine

1:11:46with this particular drug here again we

1:11:48already know that the adverse effect out

1:11:49of this one is already what we've

1:11:51discussed it is going to cause a

1:11:53compensatory reflex tachycardia we

1:11:55should already know that mechanism and

1:11:57have it understood is that it reduces

1:11:59resistance drop blood pressure and

1:12:00creates a compensatory stimulation of

1:12:02baroreceptors to increase heart rate the

1:12:04other thing which is a little odd with

1:12:05this one

1:12:07is that I like honestly it's not

1:12:09completely understood it may cause like

1:12:11an auto antibody production but it

1:12:13actually can cause a drug-induced lupus

1:12:15so watch out for what's called drug

1:12:17induced

1:12:21um SLE

1:12:23here's the one more thing

1:12:25hydralazine does prefer so it does have

1:12:28more of a profound stimulates it's more

1:12:32profound to be able to work and inhibit

1:12:34arteries so when it when we actually

1:12:36compare this it actually will inhibit

1:12:38arteries

1:12:40and cause them to vasodilate way more

1:12:43then it'll actually inhibit veins but

1:12:45nonetheless it does have the ability to

1:12:48inhibit veins very minimally

1:12:50so if you inhibit veins what we'll talk

1:12:52about in a little bit here is another

1:12:54adverse effect from actually inhibiting

1:12:56veins is you reduce preload if you

1:12:58reduce preload you reduce the return of

1:13:00blood to the heart that reduces the

1:13:02stroke volume cardiac output and blood

1:13:03pressure if a patient goes from a supine

1:13:05to seated or a seeded to standing you're

1:13:07trying to fluid shift generally those

1:13:09patients would have an increase in

1:13:10maintenance return if you Vino dilate

1:13:12them they would lose their venous tone

1:13:13they don't have a good venous return and

1:13:15so because of that a potential adverse

1:13:17drug reaction from this as it may cause

1:13:19Ortho stasis

1:13:22another thing about this drug that

1:13:23happens to be safe in pregnancy which is

1:13:24also pretty cool but we'll talk about

1:13:25that a little bit later

1:13:26okay so that's hydralazine

1:13:29the next one

1:13:31is and there's another drug in this

1:13:33category called minoxidil but we don't

1:13:34really commonly utilize that anymore

1:13:36unless you're using some hair like me so

1:13:37you can use that as like Rogaine but the

1:13:39next one here

1:13:40is that we're going to put this in the

1:13:42fourth category here so the fourth

1:13:43category so these are the ones that

1:13:45actually work to increase nitric oxide

1:13:48so they work they work to increase

1:13:50nitric oxide which helps to stimulate

1:13:54guanolocyclase which helps to increase

1:13:56cyclic GMP these are called Nitro

1:14:00dilators

1:14:02now

1:14:04with these Nitro dilators there's

1:14:06actually a couple of them the one that's

1:14:08primarily going to dilate arteries is

1:14:11going to be what's called nitroprocide

1:14:12so there's another drug here called

1:14:14Nitro proside

1:14:17now nitroprocide is an interesting drug

1:14:19okay it does cause intense arterial or

1:14:22vasodilation

1:14:24one of the downsides to this drug I

1:14:27don't ever use it because of this is it

1:14:30can give off a cyanide molecule and this

1:14:33can actually lead to cyanide toxicity so

1:14:37if you think about that imagine why that

1:14:38would be problematic so generally

1:14:40cyanide can actually be taken up by the

1:14:42mitochondria and it will inhibit the

1:14:45electron transport chain so it's going

1:14:46to inhibit the electron transport chain

1:14:48now the electron transport chain isn't

1:14:50going to be able to take oxygen utilize

1:14:52that and then make ATP this is inhibited

1:14:55now and so because of that what does

1:14:57your body shift into utilizing as an

1:14:59energy source it starts you know

1:15:01undergoing anaerobic glycolysis and so

1:15:04because of that what happens is the

1:15:05result of the cyanide toxicity is that

1:15:07the patients May develop what's called

1:15:09an increase in lactic acid so they can

1:15:11have what's called lactic acidosis as a

1:15:14potential adverse effect

1:15:15so you can see cyanide toxicity with

1:15:18high doses you can see lactic acidosis

1:15:20with high doses

1:15:22a secondary of the cyanide toxicity

1:15:23there's one more thing

1:15:26cyanide is not the only problem here

1:15:28it's also been shown that this drug

1:15:32if you take the coronary vessels here so

1:15:34here's going to be the coronary vessels

1:15:35here's a coronary vessel and it's

1:15:37splitting and I'm going to have one

1:15:38going here and I'm going to have another

1:15:40coronary vessel kind of going this way

1:15:43okay

1:15:45let's say here there's a plaque

1:15:48in this part of the vessel

1:15:50okay and there's no plaque in this part

1:15:53of the vessel

1:15:55what nitroprocide will do is it'll

1:15:57actually kind of like vasodilate the

1:16:00healthy coronary vessels a little bit

1:16:01too much

1:16:03if I vasodilate this healthy coronary

1:16:06vessel in comparison to this placked up

1:16:08vessel look at the difference now so I'm

1:16:10going to kind of dilate this one up I'm

1:16:12going to exaggerate it a little bit now

1:16:13I'm going to dilate this puppy now this

1:16:17vessel is under much lower pressure this

1:16:19vessel is under much higher pressure

1:16:20where is the blood going to want to go

1:16:23it's not going to want to go down this

1:16:25coronary vessel that's for sure it's

1:16:26going to want to all go down this

1:16:28coronary vessel and so because of this

1:16:31this is actually somewhat dangerous and

1:16:32can actually lead to the myocardial

1:16:34cells so imagine here's a myocardial

1:16:36cell

1:16:38and then here's a myocardial cell what's

1:16:40going to happen to this poor myocardial

1:16:42cell that's getting almost no blood flow

1:16:44they can start to become ischemic and

1:16:46potentially die this is called coronary

1:16:50steel syndrome so you want to watch out

1:16:52for this too as a potential complication

1:16:54called coronary

1:16:56Steel

1:16:58syndrome

1:17:01this is another potential adverse effect

1:17:03of this drug and why I'm not a huge fan

1:17:05of this drug

1:17:07okay there is another one I'm going to

1:17:10briefly discuss it here because it

1:17:12actually does two things

1:17:14so I'm going to end up mentioning it

1:17:15twice so the next one here is called

1:17:18nitroglycerin

1:17:19now nitroglycerin what I want to do is

1:17:21I'm just going to write one particular

1:17:22thing here

1:17:24nitroglycerin does have the ability

1:17:26again to do everything that

1:17:27nitropresside does right so increased

1:17:30nitric oxide activate guanol cyclase

1:17:32increase cyclic GMP cause vasodilation

1:17:34Okay particularly the arteries but in

1:17:37order for it to be able to cause

1:17:38arterial vasodilation it has to be at

1:17:40extremely high doses so it's important

1:17:42to remember that nitroglycerin actually

1:17:44prefers to inhibit veins

1:17:47so to cause Vino dilation way more so

1:17:50than it prefers to cause

1:17:52inhibition

1:17:54of the arteries

1:17:56so arterial vasodilation the only reason

1:17:59it would actually start to inhibit the

1:18:01arteries and actually cause arterial

1:18:03vasodilation this is actually important

1:18:05so I'm going to write it here in this

1:18:05blue here is that it only will actually

1:18:07do this particular process here

1:18:10when you're at extremely

1:18:13high doses of nitroglycerin so at

1:18:17extremely high doses of nitroglycerin

1:18:19then you will start to get more arterial

1:18:21vasodilation and so that's why

1:18:23nitroglycerin technically can't be in

1:18:24arterial vasodilator but it has to be an

1:18:26extremely high doses like upwards of

1:18:28like 300 400 mics of nitroglycerin to be

1:18:32able to really get a vasodilatory effect

1:18:33of the arteries okay so so far with

1:18:38arterial vasodilators we have covered

1:18:40the non-dihydropyridine which is very

1:18:42mild for aptamil detizing they're mainly

1:18:44inhibiting heart rate inhibiting cardiac

1:18:46contractility we talked about

1:18:47dihydroperating very powerful

1:18:49vasodilators amlodipine nifedipine

1:18:51nicartipine pneumodipine clovideopene we

1:18:53talked about those then we talked about

1:18:55the ones that directly act on the vessel

1:18:58to increase cyclic GMP hydralazine

1:19:00minoxidil and then we talked about the

1:19:02ones that increase nitric oxide which

1:19:04activate guanocyclase and increase

1:19:05cyclic GMP and all of these things help

1:19:07to relax the vessel that would be

1:19:09nitroprosite and that high doses you can

1:19:11dilute the arteries with nitroglycerin

1:19:14all right so we talked about the

1:19:15arterial dilators right we talked about

1:19:16them pretty in depth we talked about the

1:19:18non-dihydropriating the dihydropyridine

1:19:20we talked about hydralazine and we

1:19:21talked about Nitro peroxide

1:19:22nitroglycerin the venodilators are not

1:19:24really that many and they're not really

1:19:26super powerful at treating hypertension

1:19:28to be honest with you but we're going to

1:19:30briefly mention them for the sake of the

1:19:32you know completeness of the lecture but

1:19:35when we talk about Vino dilators one of

1:19:37the concepts here is that whenever you

1:19:39kind of work to dilate the veins we've

1:19:40already kind of mentioned that calcium

1:19:43channel blockers have a very mild effect

1:19:45on the veins in dilating them

1:19:47but there is this same mechanism over

1:19:49here on the veins much more powerful

1:19:52with respect to this

1:19:54so because of that there is this enzyme

1:19:56here called guanol cyclase

1:19:59and again guadalocyclase when it's

1:20:02activated can take and turn what's

1:20:04called GTP into cyclic GMP that can work

1:20:08to act on protein kinase G and protein

1:20:12kinase G will work too inhibit this

1:20:15particular smooth muscle from

1:20:16Contracting

1:20:17now if I give a drug that works to

1:20:20increase nitric oxide that will

1:20:23stimulate the guanolocyclase increase

1:20:26the conversion of GTP into cyclic GMP

1:20:28increase protein kinase G activation and

1:20:31inhibit the smooth smooth muscle cell

1:20:33from Contracting

1:20:34so because of that really it's this kind

1:20:37of concept yes hydralazine may be able

1:20:39to directly activate the guanolocyclase

1:20:42and the veins but again I want you to

1:20:44think about it more as an arterial

1:20:45vasodilator very minimal venous dilation

1:20:49the primary thing here is we're left

1:20:51with the Nitro dilators and we've

1:20:52already talked about nitroglycerin and

1:20:54we said that's a primary venodilator the

1:20:57other one that we're going to talk about

1:20:58is called an isosorbide dinitrate let's

1:21:00talk about those so for the venodilators

1:21:04they're not super powerful

1:21:05antihypertensives but we already talked

1:21:07about the Nitro dilators for the

1:21:08arterial system nitropresside and then

1:21:11nitroglycerin at high doses the

1:21:13venodilators will put this as the fifth

1:21:16category this is another Nitro dilator

1:21:18so it's the same concept here they work

1:21:20to increase nitric oxide they help to

1:21:24stimulate guanol cyclase they help to

1:21:26increase cyclic GMP and again how what

1:21:29kind of category are they in these are

1:21:31Nitro dilators we talked about the Nitro

1:21:34dilators in the arterial system which is

1:21:36going to be pretty much what

1:21:37nitropresside and high-dose

1:21:39nitroglycerin

1:21:40for the venous dilation this is low dose

1:21:46nitroglycerin low-dose nitroglycerin

1:21:49because at low doses it prefers to Vino

1:21:52dilate than it does arterial dilate so

1:21:55that's an important thing to remember

1:21:56here now with any type of Vino dilation

1:22:00we've already talked about this but when

1:22:03you xenodilate you reduce preload you

1:22:06reduce stroke volume critic output blood

1:22:08pressure and especially if the patient

1:22:09goes from a seated to a standing a

1:22:11supine to a seated there's fluid shifts

1:22:13you reduce their venous return so one of

1:22:15the adverse effects out of this

1:22:17particular drug category with any Vino

1:22:19dilator is what you may experience what

1:22:21type of effect here orthostasis

1:22:24so this may be very common with these

1:22:27but there's one more thing with

1:22:28nitroglycerin very important especially

1:22:30for your exams because nitroglycerin

1:22:32really Vino dilates you better be

1:22:34careful with a patient who has an RV

1:22:35that can't take a joke if their right

1:22:37ventricles are just jacked up and it's

1:22:39not able to contract and it's not

1:22:41squeezing blood out of the right

1:22:42ventricle into the left heart so now if

1:22:44you have a patient who has what's called

1:22:45a right ventricular myocardial

1:22:47infarction

1:22:48why is that a problem this RV can't take

1:22:51a joke so it already is going to be

1:22:53reducing the amount of blood going from

1:22:55the right ventricle to the left

1:22:56ventricle so there's a left a decrease

1:22:58in the left ventricular preload because

1:23:00it's not going to be able to push as

1:23:01much blood to the left ventricle right

1:23:03because it's jacked up

1:23:05if that's the case the left ventricular

1:23:07cardiac output is going to drop

1:23:10and then the left ventricular blood

1:23:12pressure is going to drop your systemic

1:23:14blood pressure is going to drop right

1:23:15now

1:23:17give them a nitroglycerin

1:23:19what are you going to do

1:23:20if you give this patient nitroglycerin

1:23:22guess what you're going to do on top of

1:23:25the RV already being all jacked up

1:23:26you're going to decrease the right heart

1:23:29venous return

1:23:31that's going to decrease the left

1:23:34ventricular preload even more that's

1:23:36going to decrease their left ventricular

1:23:38cardiac output decrease the left

1:23:39ventricular blood pressure and you're

1:23:40going to kill them because you're going

1:23:41to put them into a hypotensive state so

1:23:44when a patient has a right ventricular

1:23:45Mi that can't take a joke you better be

1:23:47very careful because it can really

1:23:49really drop this patient's blood

1:23:50pressure so that's one thing avoid

1:23:52Nitros in patients who have uh who have

1:23:55a right ventricular mind the other one

1:23:58is avoid this medication in a patient

1:24:00who has what else

1:24:03who's taking a drug that acts similarly

1:24:05like a phosphodiesterase inhibitor or an

1:24:07alpha blocker so avoid this and a

1:24:10patient who's taking what's called a

1:24:11phosphodiesterase five Inhibitors are

1:24:13out there on that Viagra for the and

1:24:16then another one is an alpha blocker

1:24:17okay so an alpha blocker would also do

1:24:20this they can also block the veins

1:24:22if you do that you're reducing venous

1:24:24return extra so for this one you're

1:24:26going to significantly drop the preload

1:24:30they're going to significantly drop the

1:24:32stroke volume cardiac output and they're

1:24:34going to drop the patient's blood

1:24:35pressure so watch out because again

1:24:37hypotension may be an overt effect from

1:24:40combining nitro with a phosphodastrace

1:24:42inhibitor or an alpha blocker

1:24:45the last one here is a part of these

1:24:48Vino dilators and this is called

1:24:51isosorbide dinitrate

1:24:54really this drug is only commonly

1:24:56utilized and we'll talk about a little

1:24:57bit later it's a very potent venodilator

1:25:00so because it's a potent venodilator

1:25:02it's really good in situations the only

1:25:04true indication that we would utilize

1:25:05this for is in patients who have heart

1:25:08failure so have heart failure and are

1:25:10African-American and they're already

1:25:13taking and they're on hydralazine

1:25:16hydralazine and because this has been

1:25:20studied it's actually been shown to

1:25:22potentially be beneficial maybe even

1:25:24reduce mortality mildly and patients who

1:25:26have African-American descent have heart

1:25:27failure and already on hydralazine you

1:25:29may be able to add isosorbide dinitrate

1:25:31to reduce the preload reduce the

1:25:32congestion in patients who have heart

1:25:34failure

1:25:35all right my goodness we talked about

1:25:37all the vasodilators here and again I

1:25:40think the big thing to think about is if

1:25:41it's an arterial vasodilator what's the

1:25:43most common adverse effect reflex

1:25:44tachycardia or obviously hypotension

1:25:47with Vino dilators what's the most

1:25:49common adverse effect

1:25:50orthostatic hypotension because you're

1:25:52reducing preload so don't forget that

1:25:54all right now let's go into particular

1:25:57anti-hypertensive medications and who we

1:26:00would prescribe this to especially if

1:26:01they have an underlying comorbidity all

1:26:03right my friend so we have covered every

1:26:05drug category that is an

1:26:07anti-hypertensive agent we talked about

1:26:08some patholytics we talked about

1:26:09diuretics we talked about patients who

1:26:11we talked about Renaissance and

1:26:13aldosterone synthesis Inhibitors and we

1:26:15talked about vasodilators we went over

1:26:17all the different types of drugs we went

1:26:19over particularly how they work we went

1:26:21over some of the adverse effects we

1:26:22covered some indications of some of them

1:26:24along the way

1:26:26but what I really want you to understand

1:26:27is now that we know of all of these

1:26:29drugs we know their names they know how

1:26:31they work which is like really important

1:26:33and some of their adverse effects we

1:26:35should really now be able to understand

1:26:39what type of situations

1:26:41I could actually give this hypertensive

1:26:44agent to a person who maybe has an

1:26:46underlying comorbidity so generally

1:26:49there's an easy way if I have a patient

1:26:51who has no problems no diseases and

1:26:53we'll talk about that a little bit later

1:26:54that's the easy ones to tell them oh

1:26:56prescribe this one prescribe this into

1:26:58anti-hypertensive prescribe this

1:26:59anti-hypertensive it's more challenging

1:27:02to prescribe an anti-pretensive when a

1:27:03patient has other comorbidities such as

1:27:06the ones that we're going to list here

1:27:07and what I want you to understand is not

1:27:09just to memorize don't just memorize all

1:27:11you can give this drug or medicine

1:27:13no no why you give this drug in this

1:27:17particular situation so you can remember

1:27:18it okay and then after we go over giving

1:27:22hypertensive agents to people with

1:27:23underlying comorbidities which one's

1:27:25best

1:27:26and then we'll cover the easy one which

1:27:28is patient doesn't really have any other

1:27:29underlying comorbidities what are the

1:27:31best agents for them what are the first

1:27:33line anti-pretensives and then what

1:27:35we'll do is we'll talk about a patient

1:27:36who comes in they got a stroke their

1:27:39heart's about to explode they Gotta Die

1:27:41an aortic dissection they're peeing

1:27:43blood and nothing but a hypertensive

1:27:45emergency because their BP is one over

1:27:46185 over 126. and those situations what

1:27:51are the best agents to give we'll talk

1:27:53about that at a hypertensive emergency

1:27:55but first things first we have a patient

1:27:58here who has atrial fibrillation they

1:28:01have atrial flutter maybe they have like

1:28:03a super ventricular tachycardia that's

1:28:04chronic for them and they have

1:28:06hypertension which one about all the

1:28:08agents would be best for these patients

1:28:10and think about it

1:28:12if a patient is atrial fibrillation

1:28:13atrial um

1:28:15flutter SVT in some way shape or form

1:28:17their nodal cells are hyperactive and

1:28:19they're firing and so in these

1:28:21particular patients they're having

1:28:22increasing heart rates right which is

1:28:25going to be doing what increasing their

1:28:27cardiac output increasing their blood

1:28:29pressure potentially okay

1:28:31well then you got to go back and think

1:28:33on the nodal cells there were two types

1:28:36of things that I can modulate one was a

1:28:40beta 1 receptor so one of these was a

1:28:43beta-1 receptor actually a student read

1:28:44because it was red and looked cool so

1:28:46this was a beta 1 receptor

1:28:50and the other one was a non I'm going to

1:28:52kind of put them in a breed as

1:28:54non-dihydropyridine calcium channel

1:28:57oh okay

1:28:59well if I give a drug

1:29:01like a beta blocker

1:29:03and I give a drug like a

1:29:04non-dihydroputing calcium channel

1:29:06blocker

1:29:07what I'll do is is I'll inhibit

1:29:10this beta receptor from being stimulated

1:29:12which will try to increase the heart

1:29:13rate so I'll inhibit this process and

1:29:16I'll reduce the heart rate I'll reduce

1:29:18the cardiac output and I'll reduce the

1:29:20blood pressure and at the same time

1:29:22these patients hearts are beating really

1:29:24fast I'll treat their afib their a

1:29:26flutter and SVT because the problem with

1:29:27these patients is they have fast heart

1:29:29rates

1:29:30well if I give a drug like a beta

1:29:31blocker that'll do that

1:29:33if I give a drug like a

1:29:34non-dihydropyridine calcium channel

1:29:36blocker inhibit the calcium from

1:29:37entering into this

1:29:39nodal cell then calcium will not come in

1:29:43if calcium doesn't come in as I inhibit

1:29:45this process it's not going to be able

1:29:46to do what stimulate Action potentials

1:29:49in the nodal cells down the AV node or

1:29:50down the SC node AV no bundle of His

1:29:52bundle branches per kg system because of

1:29:55that it will

1:29:56drop the patient's heart rate drop their

1:29:58cardiac output and drop their blood

1:29:59pressure

1:30:00so because of that these would be two

1:30:02great drugs and patients who had

1:30:03hypertension Plus have some

1:30:05tachyarrhythmias so what are these two

1:30:07particular drug categories this would be

1:30:11one would be a beta blocker a beta one

1:30:16blocker so this would be things like

1:30:18metoprolol asthma law Atenolol

1:30:22bisoprolol things of that nature and

1:30:25then the second one would be what

1:30:28a

1:30:29non-dihydropyridine calcium channel

1:30:32blocker like varapamil like diltiazam

1:30:35that makes sense right so that's what I

1:30:37want you guys to be thinking about in

1:30:39this particular situation

1:30:40all right so patient has hypertension

1:30:42and they have attacker arrhythmia give

1:30:43them something that drops their heart

1:30:44rate pretty straightforward

1:30:47the next one is coronary artery disease

1:30:49and angina so a patient has some type of

1:30:51disease process where their myocardium

1:30:54right here's our myocardial cells here

1:30:56so here's the myocardial cell so these

1:30:57are the myocardial cells and this is a

1:30:59coronary blood vessel and blood is

1:31:02supposed to be moving through this

1:31:04coronary blood vessel nice and easily

1:31:06and giving off oxygen to these

1:31:09myocardial cells so that they can use it

1:31:11to generate contractions to generate

1:31:14Action potentials all of those things we

1:31:15need it the myocardial cells needed

1:31:18but if they have a big old stinking

1:31:19plaque here that's really altering the

1:31:22decreased blood flow so now there's

1:31:23decreased cerebral blood I mean so

1:31:24there's decreased coronary blood flow

1:31:25and there's decreased exchange of oxygen

1:31:28across this big fat plaque into the

1:31:29myocardial cells that's going to reduce

1:31:31the oxygen delivery to the myocardial

1:31:33cells

1:31:34if you reduce the oxygen delivery to the

1:31:37myocardial cells that can lead to

1:31:39ischemia

1:31:40now imagine that a patient also has

1:31:44another problem so here's what happens

1:31:45to coronary artery disease and one

1:31:47particular situation here we reduce

1:31:49oxygen supply because of the plaque

1:31:53right

1:31:54now here's the other problem

1:31:56a patient who has like unstable angina

1:31:58or an nstemi it's not completely

1:32:00occluded it can be partially occluded

1:32:03but now here's where it gets really

1:32:04really problematic

1:32:05if the patient's myocardial cells need

1:32:07more oxygen because the patient's

1:32:09working harder for whatever reason like

1:32:11they're hypertensive if they're

1:32:13hypertensive now their myocardium has to

1:32:15work harder to pump blood out of the

1:32:17heart and so because of that with that

1:32:20situation what you can get is in a

1:32:22decreased oxygen supply you can have The

1:32:24myocardium have an increase in O2 demand

1:32:29and this is a recipe for disaster when

1:32:32The myocardium is requiring more oxygen

1:32:35you don't have enough oxygen to be able

1:32:37to give to it what's the ultimate result

1:32:39here ischemia to the heart and so the

1:32:42ultimate result here is this is going to

1:32:43lead to ischemia

1:32:46and if not treated there's an increased

1:32:49risk of

1:32:50infarct to The myocardium

1:32:54so I can't change the oxygen supply in

1:32:56these patients that's where I'd have to

1:32:59go in and rip the you know stent open

1:33:00the vessel or cut the plaque out I can't

1:33:03do that with drugs but I can give a drug

1:33:06that reduces the O2 demand in other

1:33:09words the heart doesn't have to work as

1:33:11hard to pump blood out of it well how do

1:33:14I do that well let's let's take a second

1:33:16here to look here well one way one way

1:33:20is if I work to inhibit those nodal

1:33:23cells so one way is I can take the nodal

1:33:26cells

1:33:27if I block the beta receptors and I

1:33:31block the calcium channels that allow

1:33:33for flow into them right so here I'm

1:33:35going to block these channels here I'm

1:33:37going to block these calcium channels

1:33:39now calcium can't come in right so

1:33:41there's not going to be able to be