Autonomic Pharmacology (Ar) - Lec 03 - Epinephrine

Hello everyone We will specify

this video for illustration of sympathomimetics first of all ,what does sympathomimitcs mean ?

In the past video I told you about the  adrenergic receptors , do you remember them ?

Alpha 1 alpha 2 beta 1 beta 2 and beta 3 We have a rule stating that any drug activating

these receptors either all of them or  part of them is termed sympathomimetic

In other words any drug that  has an effect resembling or

mimicking the stimulation of sympathetic system Is termed sympatho …. Sympathomimetic ..something

imitating the sympathetic stimulation Okay .. this sympathomimetic family is such

a large one it has so many drugs  which we will study together

Now how are they classified ? They are classified by two

methods .. the first one is according to their  mechanism or mode of action ….the way they act

The second method is more of a  chemical one … they are classified

according to their chemical nature I tell you the advantages of each

classification and why we are doing this Acoording to the mechanisim of action

imaing if this is a nerve ending ..adrenergic  or sympathetic nerve ending releasing nor

epinephrine as you already know this norepinephrine is released to

act on alpha and beta as you already know now if the drug which is applied externally

is going directly to these receptors and I told you it doesn`t have to stimulate

all of them it can only stimulate some  of them such as a certain subtype

if the drug is stimulating alpha and beta  at the first hand then it is called direct

acting sympathomimetic , it acts directly however it can act through another indirect

method it may not go to the receptors but it go  to the nerve ending releasing norepinephrine

in this method it didn`t go the receptors  directly instead it went to the norepinephrine

releasing it from the nerve ending but is there another method ? that`s possible

you can disable the enzyme you know as MAO what would happen if you give me MAO

inhibitor ? this MAO enzyme is disabled so  norepinephrine present in the nerve ending won`t

get broken thus its level is increased … activating the receptors which will

result in sympathetic stimulation this is how we classify them according to mode

or the mechanism of action by which they work again … direct means it works on the receptors

… indirect means it either releases  norepinephrine from the nerve ending

or disables this MAO enzyme now we have finished the first

title … direct and indirect sympathomimetics then according to the chmical nature

we are going to see the advantage behind  this chmical classification although I

told you that we don`t care much about  chemistry Except in the narrowest limits

you know that there is an amino  acid called tyrosine this tyrosine

undergoes hydroxylation turning into dopa which is then decarboxylated into dopamine

…again this dopamine undergoes  hydroxylation turning into noradrenaline

and nor adrenaline is methylated  turning into adrenaline

this is what you had studied in biochemistry now remember that tyrosine structures has a

ring like this … we will later  call this ring catechol ring

this ring has OH here and OH here so  there are two OH attaching to it

this ring is preserved when tyrosine  turns into dopa then dopamine

it is kept with all of these compounds then all of these compounds dopa dopamine

noradrenaline or adrenalie they all keep this original

tyrosine ring which we call catechol ring then all of these compounds and everything similar

any compound other than these having this ring is called catecholamine .. cate chol amine

but what about those that doesn`t have a ring ? if there are drugs stimulating sympathetic system

and they don`t have this ring then  they are called noncatecholamine

why are we saying this ? when a drug have this catechol

ring like these drugs dopa dopamine and so on this ring as you can see has two OH groups and

these OH groups are water soluable  so they are the ones making

these drugs water soluble and you know  that anything in order to be absorbed

any drug swallowed orally in order to  be absorbed and reach the circulation

it shouldn`t be water soluble  instead it should be lipid soluble

so these two OH groups are the reason  why these drugs are not absorbed orally

and these two Oh groups are also the reason why  these drugs can`t cross the blood brain barrier

when we are asked why can`t these  drugs cross the blood brain barrier ?

we say because it contain catechol ring but truth  to be old it is not because of the catechol ring

it is the two OH groups and sometimes  there are a third one .. they are the

ones preventing drugs from being absorbed  or crossing the blood brain barrier

not only this but any catecholamine  can be broken down by MAO and COMT

and it is destroyed within minutes  3 or 4 minutes at the latest

so we are classifying catecholamine  sometimes according to chemistry

whether they contain catechol  ring and called catecholamine

or desn`t contain catechol ring  and called non catecholamine

thus if you say your drug is catecholamine  then take into consideration that it has

these four qualities I told you about any catecholamine .. any drug containing

this ring is not absorbed orally cannot cross the blood brain

barrier .. destroyed by MAO and COMT doesn`t last for minutes in your body

but is there a way for these drugs to be absorbed  and cross the blood brain barrier and so on ?

of course there is a way … remove these two  OH groups that are making these problems

however when you remove these OH groups from the  structure it is no longer called catechol ring

so you converted this compound from  catecholamine into noncatechoamine

okay .. this was about the  classification of sympathomimetics

now when we study the sympathomimetics  we will pick the drugs in order .. and

discuss them one by one we will begin with the most important

member of the family which is adrenaline the most important drug in the family is

always called prototype .. Prototype when you see a large family of drugs and

there is one major important drug it is always called prototype

then adrenaline .. it is the  prototype of all sympathomimitics

so we will discuss it in detail and the rest  of drugs will be explained in relation to it

one or two line in relation to it … thus  we will discuss adrenaline in detail

now lets talk about this adrenaline first of all adrenaline is not the

scientific term the scientific term  is epinephrine .. epinephrine

what is its story ? epinephrine is the chemical transmitter that you

know present inside sympathetic nervous system not only this but it is the one released from the

gland you know as suprarenal medulla so it is natural in your body

when they discovered it in nineteen  hundred or in eighteen ninty five

they could isolate the epinephrine  or extract it from the suprarenal

and they later could synthesize it  in labs .. when they synthesized

it in labs in 1904 ninteen zero four the company which chemically synthesized

it … it called it adrenaline thus this adrenaline had become

his trade name .. hence if you want to  be scientifically exact use epinephrine

the trade name is adrenaline but since it is  a very old well known name then books are now

using these two names interchangeably with each other so you can see both

names in books they are both correct still the more scientific name is epinephrine

okay … for each drug scpecially when it  is a prototype and an important one

you will have to talk about a group of  headlines so we don`t get confused

the first headline is chemistry …  of the drug we are talking about

two .. pharmacokinetics and we will  explain what does kinetics mean soon

three the mechanisim of action … how does it

work in your body ? four .. what are its

uses … in which diseases you need it five .. how do you give this drug ? in

other words administration ? how can you  administer this drug ? orally ..by syringes

or in what way ? six what are the

adverse effects that we don`t desire adverse effects are sometime called side effects

however the term adverse effects is better because  it mean they are undesirable unlikable effects

seven … the contraindications …  contraindications means specific

situations in which a drug should not be used eight if there are certain precautions .. warnings

and recommendations during drug  administration so you don`t cause preoblems …

what do you think is the safe drug safe drug is the drug which

the patient hasn`t taken yet once the patient receives a drug from you or it

enters his body then it has become unsafe you can`t get it out

that is why we are teaching you all of these  headlines so you know what you are doing

now back to adrenaline … let`s  begin with its chemistry

first of all and as I told you before ..  adrenaline is something natural in your body

here it is formed in the never ending and in  the suprarenal gland …. Thus it is natural

okay ? it is natural and its chemical  structre contains this ring which I told

you about called catechol ring and has OH groups … so it is

natural catecholamine in my body but then do you think that adrenaline

present in this bolus is extracted from humans ? of course not … it was chemically synthesized

by a drug company and when it was firstly

synthesized by this company .. it was in  the form of crystals like sugar crystals

the sugar we eat .. the pure adrenaline  or epinephrine is originally crystals

like sugar crystals but it order to be

admistered it must dissolve in water so the company dissolved it in water

and released it in small boluses like this but when the company released it in boluses

they observed something important they observed that when adrenaline

crystals dissolve in water they  don`t remain as such for long time

because they are unstable ..unstable means they  are rapidly broken or oxidized … they change

so if adrenaline remains in its bolus or if you  draw it but left it the syringe for long period

it might be oxidized by the air sometimes it  is not the air but it is the light itself

and this process is called photoionization

so that is why sometimes  when you draw epinephrine

but keep in mind that when you draw epinephrine by  a syringe its colour should be clear like water

this is the sound epinephrine not the expired  however sometimes you may see a bolus like this

it is also epiniphine … I`ll put them both  beside one another and hopefully you can see

and spot the difference sometimes you see another

epinephrine blus but its color is darker if you draw this darkcolored bolus by the syringe

its color will be like this .. tea color where did this dark color come

from ? it is because this one is expired … long  period had passed so it is damaged by light

or if it was exposed to air  then it is damaged by oxygen

this brown compound you see is  called adrenochrome … adrenochrome

this adrrenochrome is not adrenaline  … adrenochrome … this is toxic .. this

brown compound is toxic in other words when you draw

adrenaline by the syringe if you noticed its  color has changed then don`t administer it

this one is expired and it is no longer of use okay … when the company made epinephrine

and dissolved it in the bolus they made this bolus one milli

this is the bolus … they designed it to  contain one milli .. one milli liter

and they dissolved in this  one milliliter one milligram

so it is one milligram  dissolved in one milliliter

this concentration means it  is one per one thousand

because if you dissolve one gram in one milliliter  …. Gram in milli .. then this is one to onw

but you dissolved one milligram in one milliliter  …. One milligram is one per thousand of a gram

so the concentration in this  bolus is one per thousand

when I tell you that we use epinephrine solution  with a concentration of one per thousand

it doesn`t mean that we dilute  this bolus by one thousand

we don`t dilute it with water the  compay is already producing them

diluted by one thousand they are ready for use so this bolus is a one per thousand solution

… this is about its chemical composition ... we  said that it is a natural catecholamine and I told

you how it is manufactured and produced now let`s discuss the second

headline … pharmacokinetics When we say pharmacokinetics … kinetics

means the motion of the drug ..when you say  kinetic it means the motion of something

what does motion mean ? it means four topics  which are absorption how about its absorption

Distribution … how it spreads throughout  the body and to which tissues

Metabolism .. how it gets broken Excretion ? from where does it

exit ? and in what form ? Now about the absorption … I

told you adrenaline has catechol ring Could it be absorbed orally ? can I make

adrenaline pills ? the answer is  no because the catechol ring is

preventing its absorption not only this … it is not only prevented by the catechol

ring…but you also have in your  intestine MAO and COMT enzymes

so even if it didn`t contain catechol  ring ..MAO and COMT would destroy it

before it reach the circulation Then its oral absorption is not

available .. so what about the skin  … can I put adrenaline on my skin

I`ll tell you later it causes vasoconstriction  so its absorption is very minimal

Because when it makes vasoconstriction  this area won`t have sufficient blood so

its absorption is decreased But what about the eye ? can

we make it eyedrops We used to say that if adrenaline

is made into eyedrops and installed  in eyes it woldn`t be absorbed

Why ? they said because tears is  alkaline and it destroys adrenaline

Later it was found out this isn`t  scientifically accurate … because adrenaline

can be indeed absorped into the eyes Not only absorbed but it may also reach

the heart resulting in systemic effect But anyway its absorption into the eye is

little …. So it could be absorbed via conjunctival  sac in the eye but its absorption is little

They later made a better form of adrenaline  with better absorption called di pivalyl

adrenaline ..di pivalyl adrenaline This word di pivalyl refers to better

absorption into the eyes .. so it could be  available when we need it for the eyes

So there is no oral absorption ..skin  absorption is sluggish very little amount

is absorbed due to vasoconstriction …it could be absorbed into the eyes

but it is better to use the other  form called di pivalyl adrenaline

It can also be taken by breathing …. Breathing  means by inhalation …we take this bolus .. brake

it and dissolve it in water Then we add this solution to

a device called nebulizer … nebulizer is a  device that vapors the water by ultrasound

the patient can inhale the water vapor  containing adrenaline so it can be

absorbed by the lungs and acts locally there.. now about the second headline , distribution

when I gave you adrenaline it  spreads throughout your body

but could I ask you a question ? can it reach the CNS … can it cross the blood

brain barrier ? the answer is no …. why ? you know it can`t cross the blood brain

barrier because it has catechol  ring preventing it from this

thus it can spread anywhere but the brain … the  brain is forbidden from external adrenaline

but don`t allow anyone to trap you …. The  brain is filled with adrenaline however the

brain is locally synthesizing this adrenaline adrenaline is synthesized within the nerve body

….CNS synthesizes adrenaline and uses it  as a chemical transmitter but externally

admistered adrenaline doesn`t reach the brain does the brain contain adrenaline ? that’s certain

from where ? it is synthesized there okay … now the metabolism …. I told you that

adrenaline is broken down by something  called MAO and COMT within minutes

the bolus you take doesn`t last for  two or three minutes in your body

but in what form is it excreted ? I told you  in a previous video that adrenaline is broken

down and converted into two compounds a compound called metaniphrine if you

remember .. do you remember metaniphrine ? the other compound which is more well known

and present in your book .. it  is called valenyl mandelic acid

it is excreted in urine in this form … do you  remember when I told you that when we find high

level of epinephrine or its metabolites it means this patient may have a certain

tumor .. do you remember ? which  is called phenochromocytoma

this is about pharmacokinetics …. But  then a drug that is not absorbed orally

nor it is absorped from the skin then I have to use it in the form of

boluses … so it is administered by syringes  ….and when we use this adrenaline syringe

it is better to be administered subcutaneously  …subcutaneous means beneath the skin

then can it be given by IV route ? IV means in the  vein .. yes but it is dangerous …we fear this

it is extremely unfavorable unless it is highly  indicated in the case then you can give it by IV

there is a risk to cause a heart problem if given  by IV so it is better to give it subcutaneously

or sometimes by intramuscular route in the muscles … we fear this IV route

…because it could cause a heat problem and it  could lead to a type of dangerous arrhythmias

called ventricular fibrillation now we explained its pharmacokinetics

and how can it be administered the mechanism of action of the epinephrine

I told you that epinephrine is the natural  transmitter present in your body and responsible

for activation of the sympathetic nervous system Naturally it can activate all of these receptors

from alpha to beta all of  them by the same degree

It is not biased to any type of the receptors  ..it activates them all by the same degree

However its effect on alpha two is not  apparent … its effect can be apparent on

them all except for alpha two For some reasons

First of all is because this alpha two is  presynaptic …if you remember … presynaptic

means it is present in the nerve endings And in the central nervous system

thus adrenaline don`t reach it The dose of adrenaline we use can`t

be sufficient to stimulate alpha two receptors  which are presynaptic and somehow far away

Even if it reached them … the second reason  … even if it reached alpha two receptors

What is the function of this alpha two ? its  function in the first place is to decrease

the natural nor adrenaline release in your body So when we give external adrenaline then it should

decrease the internal norepinephrine But then external adrenailine

covers this effect That`s why we never discuss

its effect on alpha two receptor .. we always  explain its effect on alpha one and all of betas

But its effect on alpha two is not apparent and  not clinically significant nor it is important

Now when adrenaline stimulate these  receptors … do you remember when I

told you that when alpha one is activated It activates a second messenger .. do you

remember its name ? it is called G Q so  it increases a substance called IP3

Which increases calcium level … do you  remember this from the last video ?

And when it stimulates all of the betas it  increases a substance called cyclic AMP which

activates many protein kinases Resulting in diverse range of

effects according to the receptor This is according to the molecular

mechanism …so when I ask you about the  mechanism of action of adrenaline

Tell me it stimulates all of  the adrenergic receptors alpha

1 alpha 2 beta 1 beta 2 and beta 3 But if I ask you about the molecular

mechanism .. then you should tell me about these  effects on the level of alpha and beta receptors

However I may ask you about the effects  .. you told me that it activates

these receptors .. correct But what are the manifestations

of these effects o the patients ? Don`t tell me it activates the receptors

and stop ..you must tell what will happen to  the patient when we activate these receptors

I can easily summarize this and tell you when we  administer adrenaline subcutaneously it can make

all the effects you know from the past video … think about the sites and functions of alpha

and mention them Think about the sites

and functions of beta one and so on But we tend to care about the relevant

effects ..the very prominent ones When I give adrenaline bolus what

do I see Immediately ? So if we think about the

heart .. needless to say effects on the heart  are the most important effects we have

So if you hold the heart what would you see ? You can see that epniphrine immediately increases

the heart rate and increase  the force of contraction

Since it increases the heart rate then it is  termed psoitive chronotropic .. chronotropic

means it increases the heart rate Since it increases the force of contraction then

it is called positive inotropic … that’s okay ? So instead of explaining the heart rate and

contractility you can just say adrenaline is  positive inotropic and positive chronotropic

But what happens if it level  is slightly increased

This is bad it causes arrhythmia  th heart is confused .. and if

its level is increased further Arrhythmia turns into a dangerous

form of arrhythmia called ventricular fibrillation  the heart could stop and the patient could die

If this is an ECG .. cardiography of a normal  person … it continues like this .. for example

If you give epinephrine in a therapeutic dose  .. therapeutic dose means the exact required

quantity to induce the desired effect Which is like this bolus here …this

bolus is called therapeutic dose … this  milli is therapeutic or sometimes we

suffice with half of the bolus If you give this dose .. heart rate

becomes like this .. do you see this  … this is tacky cardia .. okay ?

and if its level is slightly increased … this  tacky cardia starts to be disordered .. it

becomes disordered tachycardia but if its level is increased even

further … this tackycardia turns into  something like this … this zigzag you

see is called ventriculat fibrillation and it means the patient could die

that is why I told you before that we fear to give  adrenaline by IV route ….because in the vein ..

it can reach the heart suddenly …  before it is broken down here or

there …all the quantity reach the heart now you can`t ensure its effect … sometimes

it suddenly causes ventricular fibrillation  specially if it is an IV overdose

that is why we fear it this is about the heart but what do you

think of adrenaline effect on blood pressure ? normal blood pressure is one hundred twenty for

systolic blood pressure and diastolic is eighty … it can be elevated up to one hundred forty and

up to ninety and still be normal allow me to draw your attention here

if this is the systole and this is  the diastole …. Systolic diastolic

if I may ask you what is the major determinant  of systolic blood pressure ? which force

controls systolic blood pressure ? if you are good in physiology then

you know the major force controlling  the systole is the cardiac output

but again what is the major  determinant of diastolic blood

pressure ? which force controls diastolic  blood pressure which is the low pressure

if you remember it then you will tell  me it is the peripheral resistance

what does peripheral resistance means ? It means  your veins …. still what does this mean ?

is it because of vasoconstriction  or vasodilatation … this is what

controls the peripheral resistance and I told you before that epinephrine

administration stimulates all of the  receptors in your body alpha and beta

and I told you that it increases  the cardiac output

thus it is reasonable to say systole will  grow up because it increases the cardiac

output which is the major determinant of  systolic blood pressure …not only this

but it also causes vasoconstriction in blood  vessels … most of the blood vessels except for

skeletal muscles blood vessels and  coronaries they contain beta two

now cardiac output plus this  vasoconstriction both increases the systole

but vasoconstriction is not the major force instead it is the cardiac output because it is the

major determinant of systolic blood pressure now there is a problem

because epinephrine is causing vasoconstriction  in some of the blood vessels while it causes

vasodilatation in other blood vessels which is skeletal muscles blood vessels

but does this mean the forces determining the  peripheral resistance are somehow equal ?

no they are not equal it is said that this therapeutic dose …this

one bolus or the half bolus that you administer affects beta two that is present in skeletal

muscles more than alpha so in the therapeutic dose

regarding your arteries ….the effect of a  therapeutic dose on beta two is more prominent

than it is on alpha …this leads to more increase  in vasodilatation than vasoconstriction

resulting in decreased peripheral resistance  with the therapeutic dose consequently

diastolic pressures goes down like this so after you administer a bolus or half bolus

of adrenaline …you will see this figure systole goes up and diastole goes down

..so you may find blood pressure has now  become one hundred seventy over sixty

do you see what happened … this  went up and this went down

however if you give a very large  dose .. two or three boluses which

is more than a therapeutic dose then beta refuses to play along

arguing that it only responds to  the therapeutic dose and no more

so once you go over the therapeutic dose alpha  one starts to dominate all over the body

and beta two disappears … not  disappears but hides ….alpha covers it

and now the majority of the peripheral  resistance is under the control of

vasoconstriction …with the high dose this means with high doses periphral

resistance goes up so with a high dose

the graph becomes more like this systole is increased and also diastole

is increased .. this occurs with high doses  of epinephrine like two or three boluses

this is its effect on the blood  pressure …. And That`s why you

shouldn`t rush to answer such questions is you are asked about its effect on blood

pressure don`t say increase nor decrease instead be organized like this

tell him it is according to the given  dose …..therapeutic dose which is a

bolus or half a bolus increases systole and

decrease diastole then illustrate large dose more than a therapeutic dose

increases both systole and diastole together why ? because in this situation alpha one

predominates in high doses leading  to generalized vasoconstriction

increasing the peripheral resistance  and the diastolic blood pressure

okay ? this is about its  effect on the blood pressure

so lets see its effects on the other systems now I can be very brief … why ? because all

effects present on the table in your book  can occur … all effects you know can occur

so let`s remember the most common what do you think of the bronchi ?

you will tell me I remember it  has beta two… correct … but what

is the function of this beta two ? it causes Broncho dilatation …it widens

the bronchi …if the airway is narrow beta  two widens it through Broncho dilatation

still there is something important …. If  this is a cross section in the bronchi …I

told you beta two causes broncho dilatation here are bronchial glands ..these bronchial

glands secrete fluid … this is the fluid  irritating you and it is called sputum

bronchial asthma patients always cough  excreting sputum from their mouths

these glands have neighboring  blood vessels feeding the gland

which group do these blood vessels  belong to ? are they considered

skeletal muscles or visceral blood vessels ? as long as it is not a skeletal muscle then it

contains alpha which causes vasoconstriction so epinephrine cause broncho dilatation on the

bronchi by beta two receptors while  it suffocates these blood vessels

and when these blood vessels are  suffocated by vasoconstriction

these glands don`t have enough blood supply thus they stop secreting the fluid decreasing

sputum production and this is  very good for asthma patients

or patients with acute bronchial  episode … the patient who is

coughing a lot and is about to have asthma this effect is very good for them and this

effect is called bronchial decongestion .. the word congestion means blockage and

decongestion means to removes this blockage this is on the level of the bronchi

what about its effect on the CNS ? what happens  when this adrenaline reaches the brain ?

watch out ! watch out ! don`t let them fool you it doesn`t go nor it reach nor it has anything

to do with the brain it flows with the blood

indeed but it doesn`t cross the blood  brain barrier nor enters brain tissue

it has nothing to do with the brain okay … what about its effect on the

eye ? how does adrenaline affect the eye ? lets draw the eye and see its effect their

This is the iris.. Naturally This is a coronal  section This is the pupil here is the lens..

this is the suspensory ligament of  the lens and this is the cilliary

body on both sides.. It turns like this. This part is called cilliary body which

holds the lens of the eye It is covered with  columnar epithelium called cilliary epithelium

That's ok?.. This cilliary epithelium  contains beta two Do you remember when

I told you that it is responsible for  aqous humor secretion during running

Its function is to secrete the aqous humor  the eye fluid which fills the spaces in the

eyes And if this beta is increased and  secretes large quantities of fluid.

. The pressure inside the eye is increased and  this pressure is called intra ocular pressure..

If it is increased behind certain limits  it causes a disease called glaucoma

.. Okay.? If the intra ocular pressure  is increased more than 22 mmhg it is

called glaucoma or blue water What  is that has to do with adrenaline?

First of all how are you planning  to administer adrenaline into the

eye I told you there is an eye drops Back then I told you They thought it

couldn't be absorbed into the eye but  they later found it could be absorbed

Now when you apply these  adrenaline drops into the eye

This is the cornea and this is the whitish part  called sclera Here by the cilliary body we have

blood vessels called cilliary blood vessels These are the ones responsible foe supplying

the cilliary epithelium with blood That's okay? Adrenaline drops once they enter the eye.. They

enter from here and from here They  cause cilliary vasoconstriction

Because cilliary vessels  contain alpha Don't it have

beta? No because it is not a skeletal muscle T hey contain alpha one causing vasoconstriction

And when these blood vessels are suffocated  Epithelial blood supply is decreased

So it doesn't secrete fluid thus ocular  pressure is decreased This effect is

very useful if the patient has glaucoma Glaucoma patients with high intra ocular

pressure can use adrenaline eye drops causing  vasoconstriction in the cilliary blood vessels

depriving the cilliary epithelium from  blood so this beta two does not secrete

fluid and ocular pressure is decreased That's why we invented the eye drops I

told you about called di pevalyl adrenaline Why di  pevalyl.. To enhace its absorption into the eyes

Anyway we have more specialized drugs treating  glaucoma nowdays It could be used... It is

not wrong However when we discuss glaucoma we will mention more recent and more effective

drugs Better than this one But anyway adrenaline  still have a benefit when it comes to red eyes

If someone complains of constantly red  eye and he doesn't like its appearance

because it is always congested Then we can give him adrenaline for a

better look as it causes vasoconstriction  in these vessels Sclera becomes clear..

. so among the advantages of adrenaline is  its use in the red eye.. So gluacoma and

red eye as it decrease ocular tension  and makes the sclera more whitish

this is about its effects on the eye …  and you can always predict what happens

in the other systems without much effort for example if I ask about the uterus …you`d

tell me if the woman is pregnant then her uterus  have mainly beta two which causes relaxation

what about the hand ? you`d tell me that  my skeletal muscles present in my hand

contain beta two which is responsible for  tremors so it can cause some tremors …

.. however all of these effects are somewhat  temporary as I told you it is broken down

within minutes by MAO and COMT how does it affect blood sugar ?

blood sugar means we are talking about the liver  ….the liver has something called glycogen

and here is beta two which is  responsible for liquefying this

glycogen so it increases blood sugar what about blood potassium ? it

activates beta two and beta two moves  potassium from blood into tissue

causing hypokalemia ….but again all of these  effects are temporary ….they won`t last long

enough to harm he patient because injection effects

don’t last for minutes as I told you now we have discussed it effects …all the major

effects that happens when we use epinephrine after this illustration can you tell me in what

situations do we need this epinephrine ? we always begin with pharmacological effects

in order to prepare your mind for  the following concept which is uses

now I`ve prepared your mind for some  of its uses ..based on its effects on

the body and how it can be administered number one … let me ask you first ..before

we dwell into details ….how long does this  bolus last ? it is broken down after minutes

then could we use it for treating chronic  diseases ? long lasting disease ? or

can we use it only I emergency ? since it is broken down within minutes

then it is reasonable to use it in emergencies among the emergencies which we need adrenaline

for … something called acute anaphylactic shock what does anaphylactic shock mean ?

you will hear about it very often in pathology  and in micro biology and many others

this is a type of hypersensitivity  called immediate hyper sensitivity

very dangerous type of hypersensitivity  called immediate type

for example some people have penicillin allergy ..  or bee bite allergy … and many other allergies

this circle is something called mast cell …  mast cells in your body are storing such a

cursed compound called histamine in some allergic patients ..when

they receive a penicillin injection …  penciling go an pop this mast cell

through a certain mechanism that  you will study later in detail

it is not our rule now to discuss the  mechanism of anaphylactic shock …I

only need you to know that penicillin pops  this mast cell if you are allergic to it

so histamine is released …this cursed histamine  kills you …because it cases severe brocho

constriction and sever vasodilatation that is why allergic patients receiving

a penicillin injection …their  faces immediately change

before you finish your injection ..during the  injection .. that`s if he is allergic to it

and by the way this allergy is not very  common it is only three per ten thousand

which means among each ten thousand humans there  are only three who have penicillin allergy

so it is not very common as you may think if this patient is allergic his face starts

to turn red ..his voice change ..and  if you continue he would collapse

he would have a syncope from the sever  vaso dilatation caused by histamine

in this situation …the only one quick and  emergent savior is an epinephrine injection

why do we use epinephrine in this situation ? because it performs two effects that oppose the

effects caused by histamine first of all its effect is very

rapid .. it immediately saves the patient  from this immediate hypersensitivity

epinephrine causes bronchodilatation and  vasoconstriction in most of the blood vessels

it reverses the two effects cause  by histamine that is why it is

called physiological antagonist antagonist means the opposite … the

physiological opposite of histamine this situation may have only one treatment

which is a bolus of epinephrine in this situation you are in rush

…so can you give it intravenous ? No I`m still insisting on how dangerous it

is to give epinephrine through the IV route So should we give it subcutaneously ? this

is possible however subcutaneous injection  might be a bit slow while you are in rush

That is why the best route for  epinephrine administration in this

situation is the intramuscular route Intramuscular in the muscles ? where exactly ? in

the lateral thigh muscle Thus we meet halfway

You didn`t give epinephrine through  IV route exposing the patient to

the danger of ventricular fibrillation Nor you gave it subcutaneously which is slow

So you chose a midway route … so we meet halfway You may then have an MCQ stating the best route

of administration of adrenaline  in cases of anaphylactic shock

immediately Pick the Intramuscular  route in the lateral thigh muscle

okay ? so that some companies are now producing

adrenaline in the form of auto injectors auto injector means it is already loaded

in a covered sterile syringe so it can be  readily available in schools or other places

at which people may experience this form of  allergy due to some food or bites or whatever

we don`t have time to call an ambulance  which may come after three hours

another ten hours to deliver  the boy to a hospital who may

not survive for another quarter or half an hour so they are now producing preloaded epinephrine

thus it can be readily availabe for use if a problem occurs you can use this epinephrine

immediately in the lateral thigh muscle saving the life of the patient as

if something never happened okay … this is its first use

the second use of epinephrine …people howe  experience something called acute bronchospasm

from it name you can predict its nature  … a young child with a common cold

if this is the larynx.. like this ….our  larynx has a relatively wide lumen

so when you cough a lot …even if some inflammation  and edema occurs and the wall becomes swollen

the airways is still sufficient ..  it is not dangerously narrowed

however in children the larynx or the airways is  naturally narrow …so when the child have a common

cold and remain coughing for the whole night this continuous cough could lead to inflammation

in the wall of the broncho pulmonary  tree ..specially in the larynx

which is already narrow … its  lumen is already very narrow

once edema occurs … do you know  what does edema mean ? It means

vasodilatation as a result of this inflammation and this vasodilatation starts to leak water …this

widened blood vessels start to leak water this water causes edema so the airway swells

and this swelling results in even narrower  airways the child can no longer breath

so he is brought to your clinic with a bluish face  from a respiratory distress that can kill him

this is emergency … the immediate  management is to give an adrenaline

bolus subcutaneous or intra muscular sometimes it is given by inhalation

in this situation we sometimes empty the  bolus on half cup of water in the device

I told you about called nebulizer and through a mask the child inhales

the vapor containing epinephrine and what does the epinephrine do ?

the epinephrine immediately dilates his bronchi  .. not only this but it also suffocates these

blood vessels responsible for the edema when they are suffocated edema is decreased

and when edema is decreased  the wall returns to normal

the air pass effortlessly …  and the episode goes away

of course we won`t allow this boy to  leave like this instead we prescribe

him some regular medications to prevent  this episode from occurring again

and instruct the mother on the  management of this episode

we tell her about more specialized  medications ..like those

specifically acting on beta two an inhaler for example … this

inhaler acts on beta two it is not reasonable to let

her come from time to time the hospital  for saving her child by adrenaline

so we tell her this inhaler is a  beta two agonist or stimulant

if this episode occurs once again you  can use this beta two inhaler hoping for

some bronchodilation improving the condition however the epinephrine is still more efficient

… don`t forget epinephrine doesn’t  only cause bronchodilatation

it also causes vasoconstriction in the blood  vessels responsible for edema and swollen

walls which is the origin of the problem this is the second case … the third case

third case is the cardiac arrest  …cardiac arrest comes in various types

a fresh medical student thinks of cardiac  arrest as a general word …. But in reality

cardiac arrest has so many types at least you know that cardiac

arrest means ineffective pulsation if you try to feel the pulse you don`t feel it

either the heart stops completely … flat line  like this nothing too see … just a flat line

or this cardiac arrest can be  ventricular fibrillation … zigzag

lines like this on the cardiograph sometimes you might see actual cardiograph

like this .. it means there is electricity electricity is present but no pulsation an so on

so for now cardiac arrest means  ineffective pulsations for many

reasons but they are not our concern generally when the heart had a problem

and we couldn’t feel the pulse we used to  give the adrenaline injection intracardiac

we used to load one two or  three boluses of epinephrine

then we replace this needle with a  longer one like that of a cannula

or cannula trocar and we give it intra  cardiac hoping for stimulating the heart

as you already know the heart has beta  one so you can wake the heart up

this is called resuscitation  …waking up … waking the heart up

but then they said this is not right … this  process is not correct … the process of injecting

adrenaline intra cardiac in cardiac arrest cases hoping for waking the heart up … is not right

why not right ? they said cardiac arrest  cases when the heart stop beating and

the circulation becomes stagnant there is an immediate release of

vasodilator mediators …thus you can find  out that the circulation of the collapsed

patient with a stopped heart is dilated … that`s why if this person dies … the forensic

pathologist writes down a well known  phrase you all know from the news

… when they say that the cause of the death  is extreme drop in the blood circulation

and a sudden stop of the heart muscle sudden stop of heart .. ok the heart stopped

and blood circulation means there was a vaso  dilatation leading to circulatory failure

because there was a release of vaso  dilators metabolites which caused a

state of generalized vaso dilatation that`s why they see no benefit of

waking the heart up by adrenaline .. giving  adrenaline injection to wake the heart up

but then when the heart  wakes up and start bumping

if there is a generalized vasodilatation  then all of this process is useless

or as they say … you went  on a wild goose chase

because the heart start pumping and very  weekly while the circulation is still dilated

so the purpose is not to give adrenaline  intracardiac we don`t aim to wake up the

heart instead we have a higher purpose more important one .. which is to cause

vasoconstriction firstly in  this collapsed circulation

give a drug causing vasoconstriction in this  collapsed circulation … fix it first …. Then

you can later perform something called CPR cardio pulmonary resuscitation … compressing the

chest wall in a regular pattern and so on when you do this compression with your

hands … this this compression  that you do with your hands

if there is vasoconstriction in the circulation  … if you gave a drug causing vasoconstriction

in the circulation then by this hand compression the ventricle

bumps a little amount of blood to the brain  because you closed the prephral circulation

however if the circulation is patent  under effect of vasodilatation … then

as long as you perform a CPR all the blood that`s being bumped

will be swallowed by this patent circulation this is why new recommendations says that if

you want to use epinephrine … no problem  .. but give it by IV not intracardiac

why ? because IV means it runs in the  circulation causing vasoconstriction

this is what I aim for … and naturally it  will reach the heart ultimately stimulating

beta one however this is not the purpose the first aim is this vasoconstriction this

is why some people say since our purpose  is to perform vasoconstriction and CPR

then can we replace this epinephrine with  another vasoconstrictor drug …indeed we can

yes you can give another vasoconstrictor  drug while you perform CPR manually and

don`t be afraid it will work so the purpose in this situation

is not only to stimulate beta one .. no the purpose is to cause vasoconstriction

we sometimes ask students during oral  exams … why are we using adrenaline or

epinephrine in cases of cardiac arrest they immediately answer it is to stimulate

beta one .. this is not wrong to stimulate  beta one however this is not the purpose

our purpose is to cause vasoconstriction in this  collapsed circulation so when we perform CPR the

heart doesn`t confront all of the circulation thus these little contractions can deliver the

blood directly to the brain without  being lost in the circulation

I hope I made this clear for you The forth use of adrenaline ..do you

notice that these are all emergencies ? Do you notice that all of its uses are

for emergencies ? all of these are emergent  situations when we need to at very rapidly

However This fourth use is not an emergency Our colleague dentists know very well that dental

anesthesia contain vasoconstrictor compounds But why ? sometimes they add epinephrine to

dental anesthesia ..dental anesthesia requires  a from of anesthesia called local Anastasia

If local anesthetic is used alone ….

Let`s assume this is a tissue Local anesthesia duration is short

…it doesn`t last long in the tissue because  it is washed by the local blood vessels

When you inject this local anesthesia  alone it is washed by the blood vessels

For example how can your dentist perform a  lengthy procedure say for one hour while the local

anesthesia lasts only about fifteen minutes ? That`s why companies are now adding adrenaline

to the local anesthetic so it produces  vasoconstriction in the blood vessels

And when these vessels become  suffocated we acquire two merits

the first one is decresed bleeding So the dentist can have a better working

field while he is extracting a tooth  or whatever the bleeding is decresed

Number two local anesthetic can act now for longer  duration instead of lasting for fifteen minutes it

could now last for half or two hours accoding to the used concentration

So that some people thought about replacing this  epinephrine with another vasoconstrictor drugs

And that is okay as long as  it produces vasoconstriction

For example here we have an anesthetic cartridge

..this is the anesthesia you receive  when you are at the dentist

He put this one in the  injector and gives it to you

This cartridge comes in two types … one with red  writings over it like this one if you can see it

This red means this is anesthia  witout a vasoconstrictor

It doesn`t contain adrenaline …if you use this  one it can last for maximum of thrity minutes

However there is another one that looks exactly  the same I don`t have it now .. it Is the same

as this one except for green writing over it So the green cartridge contains adrenaline to

produce vasoconstriction or  something like adrenaline

So if you want to get a local anesthetic  from the pharmacy .. he would ask you

wether you want it red or green Red one means it doesn`t contain

adrenaline nor any vasoconstrictor The green one contains a vasoconstrictor

Now you know the difference between both samples  incase you see them during the clinical exam

Now if someone asks you why do we add  epinephrine to local anesthesia tell

him we do this for two reasons The first one is to decrease the

bleeding the second reason is to prolong  the duration of the local anesthetic

Sometimes … patients go to the dentists ..an  elder man about sixty or sixty five went

to his dentist for some procedure So The dentist gave him the local anesthesia

containing adrenaline , he was expecting  this anesthetic to last for an hour or two

Instead he was supersized when the patient told  him he feels immense pain after only fifteen

minutes and he asks for another anesthesia …the dentist gave him another one but it

didn`t help … this anesthesia only  lasts for ten or fifteen minutes

Of course you are now supersized  exactly like the dentist … why

didn`t the anesthesia last for long .. Why didn`t adrenaline produce vasoconstriction

lengthening the duration of this anesthesia ? You would keep wondering about this asking

the patient for his medical history and  you may then find out this patient has

enlarged prostate .. for example This will be explained soon

And this prostate now called benign  prostatic hyperplasia .. a common

disorder among older men about  fifty or fifty five years old

And its treatment is alpha blocker … in  order to avoid urine retention we treat

this condition with alpha blocker … .I gave you an idea about this

concept during the introduction Now look what happened … this patient

is a male aged fifty five years old and  it happens that he has benign prostatic

hyperplasia and receiving alpha blocker The urologist gave him alpha blocker in

order to avoid urine retention When he went to the dentist and

received the anesthetic containing adrenaline Now adrenaline can`t produce vasoconstriction

because this alpha receptor is  already blocked by the alpha blocker

And this Is the reason why the  anesthesia didn`t last for long

Thus if you have a smart clever dentist , he  will always be prepared for this scenario

Elder men above the age of fifty or fifty  five years before they make any procedures

They are asked by their dentists weather  they have any prostatic problem and

taking any drugs for the prostate If he confess to have an enlarged

prostate and receiving pills for this condition The phrase receiving pills for thi8s condition

means they are most probably alpha blockers accordingly the dentist should be pepared for

this situation and he may then ask him to  skip these tablets on the days he is coming

to the clinic and so on I`ve illustrated the uses

of epinephrine for you … … … … So now lets revise a little … how do you

administer adrenaline … don`t ever say oral .. it comes in boluses these boluses are given either

by subcutaneous or intramuscular injection … and by intravenous only in one

situation … do you remember it ? The only situation you are allowed

to give IV adrenaline is the cardiac arrest  except for this one we are afraid that it

causes ventricular fibrillation and kills the patient itself

Now can you expect the problems  caused by this adrenaline ?

The problems we expect which is known as adverse  effects … adverse effects are the side effects

Number one … when a patient  receive subcutaneous epinephrine

his blood pressure may be markedly increased This may be unexpected and it may turns into

cerebral hemorrhage … bleeding in the brain Number two … adrenaline can cause some

tremors … but this is not a significant effect  …after all these tremors subsides soon

Number three … adrenaline could sometimes  stimulate the heart excessively through its

beta effect causing tachycardia which may turns  into arrhythmia or even ventricular fibrillation

Cardiograph would be messed up like this … good  bye , he was kind …. May he rest in peace

Number four epinephrine could stimulate the  heart excessively while the heart is already

weakened by a cardiovascular disease like heart failure or whatever which

leads to acute heart failure acute drop  in heart functions the patient collapses

can no longer breathe and ends in the ICU five Epinephrine can lead to a condition known

as acute pulmonary edema .. pulmonary  edema means water within the lungs

Form where does this water come ? x2 You know this is the heart and this is

the lung and you know the lung receives the  pulmonary artery from the right ventricle

Then the lung sends the blood to the left  atrium then the left ventricle and then it

goes to the aorta That`s okay

Now when a patients receives adrenaline it  increases heart`s contractility so blood

is flowing in a high pressure  though the pulmonary artery

it arrives to the lung in high  pressure … thus the intra pulmonary

hydrostatic pressure is increased Then the lung tires to get rid of

this blood from the other side but it  meets a systemic vasoconstriction

as it causes vasoconstriction in the systemic  circulation which means that it increases the

contractility while it blocks the way Who is the one trapped in the middle ? it

is the lung It receives high

pressure flow and can`t get rid of it due to  vasoconstriction that`s why it leaks water

The capillaries in alveoli don`t stand this  elevated pressure and starts to ooze a fluid

The alveoli are filled with fluid and the  patient suffers now from acute pulmonary

edema or water in the lung What do you think is the

most dangerous among these ? Not only these there is still one more

You can give too much adrenaline .. for  example a plastic surgeon working on the little

finger … when he chose the type of anesthesia .. he picked a local anesthetic with epinephrine

which causes vasoconstriction  .. but he gave too much

And he repeated the injections … injection after

injection the procedure is taking  time and he is still giving these

injections containing a vasoconstrictor … this vasoconstrictors could suffocate the

blood vessels especially those on the tip Because they are very sensitive so that

this suffocation could kill the tissue  causing something known as gangrene

Gangrene of fingers … the fingers would turn very  cold their color is changed the next day they lose

its sense and now they must be amputated … they are not viable

What do you think is most dangerous  among these? They are all dangerous

As epinephrine is life saving  drug during emergencies and it

does save lives of many patients however This drug can cause major

problems itself …. And I think that the most  dangerous one among all of these effects

Is this one .. ventricular fibrillation …  because this is a dead patient ..fibrillation

means unless there is an emergent  ICU admission the patient dies

On the other hand .. cerebral  hemorrhage is indeed very dangerous

.none can deny brain bleeding is dangerous However cerebral hemorrhage could be localized

and the patient could still live He may live with a deformity

but at least he lives The others are very debatable

For example tremors .. it is nothing …  acute heart failure , he woul still live

Some water in the lungs ..  he would also still live

Fingers gangrene .. they would be amputated ,  of course it is disaster but he still lives

On the contrary this one with  ventricular fibrillation he dies

So when you have an MCQ stating  : the most dangerous side effect

of epinephrine injection is Pick this one arrhythmia and

ventricular fibrillation … arrhythmia  alone is not sufficient

Now lets shift to the next headline  ….. …. …. Which is contra indications

Contraindications means when not to use Of course you are smart enough to know

that the term contraindications  contra means the opposite of

and indications means when to use so  contra indications is when not to use

You know that adrenaline causes all of the  previous misfortunes .. so it is reasonable

not to use it in cases of hypertension Don`t give someone with high blood pressure

adrenaline because it causes hypertension itself Don`t ever give adrenaline to someone complaining

of cardiovascular problem someone with  angina … ischemic heart disease or so on

as it increases the cardiac work  which increases the anginal pain

His chest could become painful and he may  encounter an acute attack .. so don`t

Number three don`t give adrenaline in  large dose with local anesthetics

I always tell my dentist to be careful with  the amount of local anesthesia …because I

may need another during the procedure  so he woldn`t give me five cartridges

one after the other and they contain epinephrine Because this prolonged vasoconstriction

could lead to tissue necrosis So it is contraindicated to give an over dose

of the local anesthetic containing epinephrine Among the most important cases is a group of

cases called cardiac outflow obstruction What is the cardiac outflow obstruction ? they

are a group of cases which are collectively  known as cardiac out flow obstruction

Look here … this is the heart .. … …. And  this is the pulmonary artery going to the lung

..and this is the aorta for systemic circulation Any disease that hinders the flow of blood in the

pulmonary artery or the flow in the aorta Is called cardiac outflow obstruction …

this case is considered one of this large topic For example .. but let`s firstly draw the aorta

This is the aorta going out of  the left ventricle … here it

is .. let`s even draw him with a red pen This s the aorta and this is the arch … here

is the aortic valve if there was an aortic  stenosis the aortic valve was narrowed

This would be classified as cardiac  outflow obstruction ….or imagine if

this was the pulmonary artery going to the lung  and here was an embolus in the pulmonary artery

..something obstructing the flow … it is also  classified as cardiac outflow obstruction

There is a very well known cases , you  will hear about it very often during this

curriculum …. three or four times A case known as hypertrophic

obstructive cardiomyopathy hypertrophic obstructive

cardiomyopathy .. it was previously called  idiopathic hypertrophic subaortic stenosis

it is the same condition …  what is this condition ?

you already know the thickness of  the ventricular septum in normal

individuals doesn`t cross twelve millimeter or one point two centimeter this is the ordinary …

when you perform a cardiac echo  .. ultrasonic waves on the heart

the septum thickness shouldn`t cross this limit there are one per one thousand … one from each

one thousand individuals is  born with a genetic problem

thickness of this septum is increasing with  time and even cross one point seven centimeter

or seventeen millies it could cross these numbers

now when the septum hypertrophies like this  and its thickness is increased … note that

the heart hypertrophies more on the left side or the left ventricle ….while the aorta opens

in the left ventricle like this thus the thicker the septum is the

narrower this opening becomes … and blood  can`t flow smoothly from the aorta

that is why it is called hypertrophic  which means enlargement … obstructive

which means hindering the flow … cardiomyopathy refers to the

enlargement .. that`s correct ? okay now as this child keeps growing

up his problem also keeps increasing allow me to draw your attention to this

part … I like to give this case all the possible  attention because you will see it very often

so I don`t want to repeat it again this child during his childhood when he

was nine or ten …… when he runs or plays  football he doesn`t stand the running

as soon as he runs a little he feels  sweaty and slumps or collapse

that`s why his friends take advantage of him and  place him as a goalkeeper because he can`t run

he later goes to his mom and cries complaining  of not being able to match his friends

later when his mom takes him to the doctor  complaining her child can`t exert normal

efforts and becomes bluish as he tries the cardiologists asks her to perform a sonic

waves on the heart or what is known as echo when the cardiologist receives the report of

cardiac echography he observes the child  has a thickened intraventricular septum

more than one point five centimeter or  fifteen millies ..this causes narrowing

in the outlet of blood flow …thus when  this child runs or plays football

and experiences tachycardia .. blood can`t get  out because the flow is hindered by this septum

and this is the reason why  this child feels drowsy

this enlargement is increased with age … as long  as he grows up … until he his eighteen or twenty

when it reaches its maximum value that`s why .. you`ll very

often hear about some people , youth aged twenty or twenty two dying

while they are playing football despite  of having a good general health

you would even be astonished how could such  a healthy guy dies while playing football

indeed … do you know what is the  most common cause of sudden death in

young athletes healthy young athletes ? it is this condition called hypertrophic

obstructive cardiomyopathy he had this condition and it

was not diagnosed before …. The septum kept  increasing untill it reached a critical level

that blood could no longer flow to the aorta and this condition becomes prominent when he

plays football or exercises because the  heart is not able to bump all the blood out

after I`ve explained this condition for  you … do you know why I told you all of

this large intro ? so you know why this

one should never receives adrenaline why is that ? what would adrenaline do ?

it causes tachycardia .. correct ? and  increases the force of contraction

and since the septum is thickened suffocating  the aorta then how can the blood get out

especially with this tachycardia then blood can`t get out that`s why

adrenaline injection could kill this boy with  hypertrophic obstructive cardio myopathy

last one of the contra indications is thyroid  patients .. patients with hyperthyroidism

I`ll be brief while explaining this  one because it makes much sense

Thyroid patients who have hyperthyroidism they have lots of t4 and lots of t 3

When thyroxin is increased it  makes some changes to your body

Number one .. thyroxin increases  the number of beta receptors

The number of beta receptors in your body and  also their sensitivity are increased by thyroxin

Thyroxin is considered as adrenaline cousin The have the same origin in chemistry

They both originates from single  amino acid called tyrosine

Thyroxin goes to your beta receptors in  your body strengthening them increasing

both their numbers and sensitivity That`s why hyperthyroidism patients

always complains of symptoms  related to the beta receptors

They come to you complaining of shaky hands  ? why is it shaky ? due to tremors ? why

tremors ? because beta two They may complain of irregular

heart beats insomnia dizziness  irregular plus and tachycardia

Why ? because beta one in the heart  are confused by this thyroxin which

increases their number and sensitivity This is what we call sympathetic over activity

So patients with hyper thyrodism  have sympathetic over activity

due to upregulation caused by thyroxin Upregulation means it increases both the number

and the sensitivity of beta receptors Thus it is very reasonable not to

give him adrenaline … his beta  receptors are already on fire

Thyroxin is already whipping them So when you give him adrenaline you are

aggravating all of his symptoms Add to this the second reason

You already know about an enzyme  called COMT I told you once about it

Patients with hyperthyroidism have  low levels of COMT … by nature

Their COMT is inhibited …so when you use this  adrenaline bolus it won`t be easily metabolized

That`s why his level is  increased causing problems

now the five contraindications of epinephrine …  I told you about the five contra indications

not for cardiac patients not for hypertensive patients

please don`t use epinephrine in high  concentration during anesthesia so you

don`t cause tissue necrosis or fingers gangrene please don`t give adrenaline to this child who has

idiopathic hypertrophic subaortic stenosis  as he has cardiac out flow obstruction

and please please don`t give adrenaline  to patients with hyperthyroidism

for your information those five patients I  mentioned during explaining the contraindication

can you imagine how are we going to treat them ? their treatment is to block these receptors not

to stimulate them with epinephrine most of these patients I mentioned are

treated with something called beta blocker you will see that beta blocker are used for

hypertension , used for many  types of heart diseases

and used for this child .. this child with  hypertrophic obstructive cardiomyopathy

cardiologists give him beta blocker  so he wouldn’t develop tachycardia

and you will see that beta blockers are also  used as a treatment for hyperthyroidism

disease in which adrenaline  is contraindicated are always

treated with a blocker not an agonist I hope to see you in the next video

After we explained adrenaline in  detail we are going to discuss rest

of the drugs but not in detail like this  one