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 doesnt 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 didnt go the receptors
directly instead it went to the norepinephrine releasing it from the nerve ending
but is there another method ? thats 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 wont 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 dont 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 doesnt have a ring ?
if there are drugs stimulating sympathetic system and they dont 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 shouldnt 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 cant cross the blood brain barrier when we are asked why cant 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 desnt 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 doesnt 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 dont 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 dont 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 dont cause preoblems … what do you think is the safe drug safe drug is the drug which the patient hasnt taken yet
once the patient receives a drug from you or it enters his body then it has become unsafe
you cant 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 … lets
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
dont 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 … Ill 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 dont 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 doesnt mean that we dilute
this bolus by one thousand we dont 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 lets 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 didnt 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 Ill tell you later it causes vasoconstriction
so its absorption is very minimal Because when it makes vasoconstriction
this area wont 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 woldnt be absorbed Why ? they said because tears is
alkaline and it destroys adrenaline Later it was found out this isnt 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 cant 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 dont 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 doesnt 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 doesnt 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 dont reach it
The dose of adrenaline we use cant 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 Thats 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 ?
Dont 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 cant 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 Thats why you shouldnt rush to answer such questions
is you are asked about its effect on blood pressure dont 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 lets 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 dont 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 ! dont let them fool you
it doesnt go nor it reach nor it has anything to do with the brain it flows with the blood indeed but it doesnt 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 …youd tell me if the woman is pregnant then her uterus have mainly beta two which causes relaxation what about the hand ? youd 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 wont 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 Ive 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 .. thats 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 Im 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 didnt 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 dont 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 wont 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 … dont 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 dont 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 … thats 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
thats 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 dont 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 thats 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 dont 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 doesnt 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 …. Lets assume this is a tissue
Local anesthesia duration is short …it doesnt 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 ? Thats 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 doesnt 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 dont 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 doesnt 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 didnt help … this anesthesia only
lasts for ten or fifteen minutes Of course you are now supersized
exactly like the dentist … why didnt the anesthesia last for long .. Why didnt 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 cant produce vasoconstriction because this alpha receptor is already blocked by the alpha blocker And this Is the reason why the anesthesia didnt 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
Ive illustrated the uses of epinephrine for you … … … … So now lets revise a little … how do you administer adrenaline … dont 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
Thats okay Now when a patients receives adrenaline it increases hearts 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 cant get rid of it due to vasoconstriction thats why it leaks water The capillaries in alveoli dont 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 Dont give someone with high blood pressure adrenaline because it causes hypertension itself
Dont 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 dont Number three dont 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 woldnt 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 lets firstly draw the aorta This is the aorta going out of the left ventricle … here it is .. lets 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 doesnt 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 shouldnt 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
cant 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 .. thats 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 dont want to repeat it again this child during his childhood when he was nine or ten …… when he runs or plays football he doesnt stand the running as soon as he runs a little he feels
sweaty and slumps or collapse thats why his friends take advantage of him and place him as a goalkeeper because he cant 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 cant 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 cant 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
thats why .. youll 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 Ive 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 cant get out thats why adrenaline injection could kill this boy with hypertrophic obstructive cardio myopathy last one of the contra indications is thyroid patients .. patients with hyperthyroidism Ill 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
Thats 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 wont be easily metabolized Thats 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 dont use epinephrine in high
concentration during anesthesia so you dont cause tissue necrosis or fingers gangrene please dont 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