Pharmacology - Antihypertensives

hello in this video we're going to talk

about anti-hypertensives so medication

to lower blood

pressure so the heart pumps oxygenated

blood around our body the hot first

pumps um this Blood through the arteries

and this is in red here and then once

the oxygenated blood is distributed

around the body tissues the blood is

then brought back to the heart via the

veins here in blue focusing first on the

heart the heart actually pumps a certain

amount of blood each time it contracts

and this is the cardiac output the

cardiac output allows blood to flow

through the arteries and deliver

oxygenated blood to tissues before

returning back to the heart via the

veins the cardiac output it's itself has

a big impact on blood

pressure other organs responsible for or

plays a role in regulating blood

pressure include the liver lungs kidneys

and the endocrine organ above the

kidneys called the adrenal

glands when we talk about blood pressure

we are really talking about the arterial

blood pressure so the mean arterial

pressure and this mean arterial pressure

can be calculated by um having cardiac

output multiplied by the total

peripheral resistance

tpr and tpr is the resistance um of the

vessels of the archery in this

case to make things even more

complicated the blood pressure we know

has two numbers one on top called the

systolic and one number on the bottom

called the diastolic blood pressure the

systolic blood pressure is essentially

the pressure um of the arteries when the

heart is pumping blood out and the

diastolic blood pressure is the pressure

in the arteries when the uh when the

heart is filling back with blood normal

blood pressure is about

120 over

80 hypertension means high blood

pressure many things can cause

hypertension persistent untreated or

unmanaged uh hyper hypertension can have

serious

consequences and one way to treat

hypertension is by using

anti-hypertensives or medication to

treat hypertension and these medications

can be remembered by the alphabet so a b

c d and e let's begin by looking at a so

a includes ACE

inhibitors Angiotensin receptor blockers

and Alpha 1 receptor

blockers now before

focusing on these um let's just recap

some physiology so the liver produces

this molecule called

angiotensinogen uh when there's a

decrease in blood pressure in the

arteries the kidneys will detect this

and then produce a molecule called renin

now renin enters circulation and is

responsible for converting

angiotensinogen produced by the liver

into angot tensin one Angiotensin one

will then circulate around the body and

get in contact with a membranebound

enzyme called Ace or angot tensin

converting enzyme which mainly resides

in the lung tissues so Ace converts

Angiotensin one to Angiotensin

2 Angiotensin 2 is an important

regulator of blood pressure and what it

does is basically it increases blood

pressure via a number of

mechanisms Angiotensin 2 binds onto

Angiotensin 2 receptors on many

different types of cells around our body

and depending on what cell Angiotensin

binds to its effect on the body um

differs so but essentially it will

result in an increase in blood pressure

so for example some of the effects of

angiotensin 2 includes increasing

sympathy itic activity

vasoconstriction stimulating the release

of aldosterone a hormone from the

adrenal

cortex and these effects all of them

will lead to an increase in blood

pressure ACE inhibitors or Angiotensin

converting enzyme Inhibitors is a very

common

anti-hypertensive these medications can

be remembered uh by the ending pill so

for example captop Ram they all end in

pears

usually the mechanism of action of ace

inhibitor is that it inhibits Ace the

enzyme bound membrane bound enzyme and

so it inhibits the conversion of

angiotensin one to Angiotensin 2 and

because you have less Angiotensin 2

means that you will decrease blood

pressure because it's not working some

side effects of ACE inhibitors include a

dry cough

a rash nausea vomiting diarrhea angio

edema and

headache there are contraindications to

using ACE inhibitors or relative or

absolute and these include being

pregnant having bad asthma chronic cough

being allergic to ACE inhibitors having

a kidney disease particularly renal

stenosis the other medication that

starts with a is the Angiotensin

receptor blocker and as the name

suggests the mechanism of action it

blocks The Binding of angiotensin 2 to

its

receptor and so thus it will decrease

the activity of angiotensin 2 which will

result in a decrease in blood

pressure the side effects of angiotensin

receptor blockers include headache

nausea diarrhea dizziness and back

pain some contrad indications include

pregnancy renal stenosis bilaterally and

if they are allergic to Angiotensin

receptor

blockers it's interesting to note that

Angiotensin receptor blockers are

usually used as an alternative to ACE

inhibitors because people that use ACE

inhibitors getting a chronic or getting

a dry cough is quite common and so

sometimes people change to the

Angiotensin receptor

blockers Angiotensin receptor blockers

can be remembered because it us usually

ends in

sartan so for example La

sartan the

sartans anyway the final

anti-hypertensives that begin with a are

the alpha 1 receptor

blockers and these guys aim is to work

on the vessel epithelial cells so

zooming into the blood vessels here is

the Lumen of the blood vessel and

surrounding the Lumen is the endothelial

cells and the smooth muscle cells the

smooth muscle cells can contract usually

and this will make the Lumen of the

vessel

smaller or the smooth muscle cells can

relax and this will dilate the Lumin

quote making it

wider so as you might suspect when the

smooth muscle cells contract and the

Lumen becomes smaller the blood pressure

increases the smooth muscle cells that

surround the vessels have alpha 1

receptors these receptors react to

noradrenaline Adrenaline produced by the

nerve fibers or from noradrenaline

adrenaline in circulation noradrenaline

and adrenaline is same same thing as

epinephrine

norepinephrine anyway nor adrenaline

will uh can bind to the alpha 1 receptor

and this will cause or stimulate

contraction of the smooth muscle cells

the contraction of the smooth muscle

cells that around the vessel will cause

the vessel to become more smaller will

narrow the Lumen and this will lead to

an increase in blood

pressure alpha 1 receptor blockers they

block alpha 1 receptors and thus the

mechanism of action of alpha 1 receptor

is that inhibits the adrenergic activity

leading to the decrease in blood

pressure alpha1 receptor blockers also

have a role in decreasing total

cholesterol in the body thus it's a good

option for people who have both high

blood pressure and cholesterol

problems side effects include um it can

lead to

hypotension so a drastic decrease in

blood

pressure so they were the

anti-hypertensives that begin with a

let's look at the anti-hypertensives

that begin with b b it's easy it's just

beta

blockers and beta blockers are very easy

to remember because they end usually in

all

like metol andol or

L anyway beta block is

block uh what are called beta receptors

and beta receptors are important in the

sympathetic

activity so by blocking the beta

receptors you are blocking sympathetic

activity essentially so there are beta

receptors everywhere in the body we

mainly we will mainly concentrate on the

heart here

so be beta blockers can be selective and

work specifically on the heart or beta

blockers can be non- selective and work

on the periphery too such as the blood

vessels but let's focus on heart the

heart have these cells called pacemaker

cells which make up the conduction

system of the heart the pacemaker cells

regulate the heart rate so how fast your

heart is pumping the pacemaker cells can

be influenced by many things including

the parasympathetic nervous system and

the sympathetic nervous

system pacemaker cells of the heart they

have receptors on them the beta one

receptors adrenergic neurons which are

part of the sympathetic nervous system

Target these pacemaker cells and release

adrenaline and noradrenaline which will

bind onto these beta 1

receptors thus it will stimulate the

pacemaker cells to fire more rapidly

which will increase the heart rate and

because you get an increase in heart

rate you will get an increase in blood

pressure by increasing the cardiac

output further the heart itself is a

muscular organ they are made up of

cardiomyocytes which are basically the

cardiac muscle

cells the muscle cells of the heart the

cardiomyocytes are the cells which

contract and help eject blood out the

hot muscle cells also contain beta one

receptors so noradrenaline and

adrenaline released by adrenergic cells

the sympathetic nervous system can

stimulate the beta 1 receptors of the

cic muscle cells which will cause the

codic muscle cells to contract stronger

and to be exact it will lead to a more

powerful

contraction with a more powerful

contraction the hot is able to increase

cardiac output and because you're

increasing cardiac output you will

increase blood

pressure beta blockers selective for the

heart work by inhibiting beta 1

receptors the mechanism of action of

beta blockers is that they block the

sympathetic function on the Heart by

blocking the beta one

receptors and they do this by two ways

first by decreasing the heart rate which

will decrease cardiac output and then

decrease blood pressure or they will

decrease the myocardial contraction the

strength and thus decreasing CTIC output

which will subsequently decrease blood

pressure side effects of beta blockers

include bradicardia fatigue hypotension

decrease in libido impotence and Bronco

constriction contradiction include

obstructive lung disease and peripheral

vascular

disease so that was the

anti-hypertensives with B let's look at

C anti-hypertensives and the C's uh are

the calcium channel blockers most names

um for calcium channel blockers they end

in or sound something like

deine um or like um Mill so for example

Verapamil um but these guys are kind of

hard to remember but hopefully you get

the idea anyway in order to understand

calcium channel blockers we need to

understand calcium and its role in the

body when you think of calcium think of

muscle contraction think of

excitability calcium channels are

important channels in our body that

allow the movement of calcium in and out

of cells or uh cellular organel there

are two main calcium channels we will

talk about and these are the T type

calcium channels and the L Type calcium

channels but what these drugs do is that

as the name suggests they block calcium

channels more specifically they block

ttype calcium channels and or L Type

calcium channels so there are L Type

calcium channel blockers or ttype

calcium channel blockers or both and

it's important to know this because

these channels are found in different

parts of our body for example in the hot

going back to our past maker cells which

control the hot rate there are ttype

calcium

channels calcium activity in the past

maker cells causes the heart to pump

faster and so contributes to increasing

the blood

pressure think of ttype calcium channels

as time so t for time because the pace

maker cells of the heart control the

heart time the heart

rate and so by using the T P type

calcium channnel blockers it will block

calcium activity and thus decrease heart

rate decreasing CC output and then

decreasing blood

pressure this might get confusing but

there are three types of uh T type

calcium channel blockers these are the

phenol alkaline such as Verapamil the

benzoin such as

delim and the dihydro paradine such as

the ones that end in deine

so they they are all different but to

put it simply they just work differently

and they also work on L Type calcium

channels but anyway so for example um

here is Verapamil a common calcium

channel blocker which will block the

ttype calcium channels of the pacemaker

cells let's talk about the L Type

calcium channels which are found on

smooth muscle cells so here we have the

blood vessel which as we know contain

smooth

muscles um and here is the limit of the

vessel for example the ltop calcium

channels allow influx of calcium into

the muscle filaments which will cause

contraction this will increase the blood

pressure because it causes the vessels

to contract and become more

narrow but the L Type calcium channels

are also found in the

cardiomyocytes and thus they will

increase the power of contraction of of

the

cardiomyocytes um which will further

increase cardiac output and so blood

pressure lype calcium channel blockers

are the dihydropyrenes where that end in

deine some of the drugs from

dihydropteridine also block ttype

calcium channels and so is also part of

the ttype calcium channel

category a common example of a l type

calcium channel blocker is

neopine side effects of the DI hydrop

paradin like a lot of anti-hypertensives

are flushing headache dizziness from

hypotension palpitations and peripheral

edema Contra indications of calcium

channel blockers are congestive heart

failure heart block hypotension and

ventricular

tachicardia and this is unique to

calcium channel blockers because in

heart failure the heart is trying to

compensate

by by Contracting a lot harder and so if

you use a calcium channel blocker

specifically an L Type calcium channel

blocker you are weakening or you are

reducing the strength of contraction of

the heart and this is what you do not

want to do in people who have hot

failure so that was the C

anti-hypertensive medication the calcium

China blockless next is D for diuretics

so when we think of diuretics we think

of the

kidneys diuretics works on the kidneys

and what they essentially do is induce

diuresis cause peeing so when we pee the

water in our body it drops and this will

then uh you know drop blood

pressure so here is the kidneys with the

adrenal glands above it and the

functional unit of the kidneys or the

main players of the kidneys are these

things called nephrons and there are

millions of nephrons in the kidneys and

this is where diuretics work and it's

important to understand that the nefron

the functional unit of the kidneys they

filter things from blood and they allow

for secretion and reabsorption of things

in and out of the blood vessel so here

I'm just going to draw a a vessel a vein

let's just say a vessel and so the

mechanism of action of diuretics again

is to increase urine output decrease

fluid overload and this will decrease

blood

pressure and there are three types of

diuretics three main ones these are the

Loop Diuretics which is the strongest of

the lot the thide diuretics and the

potassium sparing

diuretics the nefron is divided into

different sections one of which is the

loop of Henley in the loop of Henley in

the ascending part there is this channel

a symptom which transports one sodium

molecule two chloride molecules and one

potassium from the nefron back into

circulation back into the blood vessel

when sodium is reabsorbed in the blood

water

follows Loop Diuretics inhibit the

transport of this this transporter by

inhibiting the movement of chloride ions

which will disrupt the whole transport

and so you don't get sodium moving into

into the blood vessel and so you don't

get water following and so you don't get

an increase in blood

pressure thide diuretics work on the

distal part of the nefron there is a

transporter here which reabsorbs sodium

and chloride together this will then

draw water back into the blood as well

which will increase the blood pressure

in the body thide diuretics block this

transporter and so block sodium

reabsorption abortion and thus water

reabsorption causing a decrease in blood

pressure in the distal part of the

nefron there's also this other

transporter exchanger which reabsorbs

sodium but secretes

potassium and potassium sparing

diuretics inhibit this uh transporter

and by inhibiting this transporter you

actually decrease the reabsorption of

sodium which means you decrease the

reabsorption of water which subsequently

decreases blood pressure but you also

prevent the secretion of potassium and

this is why it is called a potassium

sparing diuretic because you're sparing

potassium and so all these diuretics

they

essentially um inhibit sodium from going

into the blood and so you have more

sodium being peed out which means that

you have more water being peed out which

means that you will decrease blood

pressure side effects of Loop Diuretics

and thide diuretics include hypo calmia

hypo naturamia hypo vmia

hypotension

hyperemia which increases the risk of

gout

hyperglycemia

hypercalcemia metabolic alkalosis and

pancreatitis the side effects of

potassium sparing diuretics is quite

different in that they can cause

hyperemia met abolic acid dosis and

gynecomastia if you want to know more

about diuretics I have a separate video

on the pharmacology of

diuretics finally e antihypertensives is

for

endothelium reor antagonist and these

guys basically um relax the blood vessel

causing Vaso dilation which will cause a

decrease in blood pressure they work on

the blood vessel um the smooth muscle

cells contain endothelin one receptors

which when endothelin a molecule

produced by the blood vessel itself

binds onto it it will cause contraction

and narrowing of the blood vessel which

will cause an increase in blood pressure

of course well endothelin receptor

antagonists as the name suggests

inhibits this receptor which means you

don't get contraction of the vessel

which means that you will lower the

blood

pressure the side effects of endo othian

receptor antagonists include headache

peripheral edema nasal congestion nausea

hypo tension and

palpitations so that concludes the video

on the anti-hypertensive medications we

looked at um a b c d and e a for ACE

inhibitors Angiotensin receptor blockers

and um Alpha 1 Alpha receptor

antagonists and we also looked at B for

beta blockers C for calcium channel

blockers D for diuretics and finally we

just looked at e for endothelin receptor

antagonists anyway I hope you enjoyed

this video I hope it was helpful thank

you for watching

byy