Autonomic Pharmacology (Ar) - Lec 01 Part 1 - Review of physiology

Summary

This video provides a concise review of the principles of physiology of the autonomic nervous system (ANS), essential for understanding pharmacology. The ANS regulates involuntary functions and consists of the sympathetic and parasympathetic systems. The video covers the roles of higher centers, nerves, chemical transmitters, and receptors in both systems. It explains how autonomic nerves transmit signals, the significance of ganglia, the fate of neurotransmitters like acetylcholine, and the impact of various receptors on internal organs. The importance of drug selectivity and the implications of enzyme deficiencies are also discussed to aid in comprehending autonomic malfunction treatments.

Takeaways

• 😀 The autonomic nervous system (ANS) regulates involuntary functions such as those of the intestines, lungs, and heart.
• 😀 The ANS is divided into the sympathetic and parasympathetic systems, each with higher centers, nerves, chemical transmitters, and receptors.
• 😀 Higher centers in the brain and spinal cord control autonomic functions, sending signals via nerves to internal organs.
• 😀 Autonomic nerves rely on ganglia, which act as relay stations; sympathetic ganglia are near the spinal cord, while parasympathetic ganglia are near organs.
• 😀 Most internal organs have dual nerve supply from both sympathetic and parasympathetic systems, but the ratio of nerve supply can vary.
• 😀 Nerve signals in the ANS are transmitted by chemical neurotransmitters; acetylcholine is released in both systems at ganglia, while norepinephrine is released at sympathetic nerve endings.
• 😀 Receptors for neurotransmitters include nicotinic acetylcholine receptors in ganglia and muscarinic or adrenergic receptors at nerve terminals on organs.
• 😀 Drugs can target different levels of the ANS: higher centers, ganglia, nerve endings, and receptors, with receptor-level targeting being the most selective.
• 😀 Acetylcholine is broken down by cholinesterase enzymes; true cholinesterase is specific to acetylcholine, while pseudocholinesterase (butyrylcholinesterase) breaks down multiple substances.
• 😀 Deficiencies in pseudocholinesterase can lead to severe reactions to drugs like succinylcholine, used as a muscle relaxant during surgeries, resulting in prolonged muscle paralysis.

Q & A

What is the primary focus of the video series on pharmacology?

The primary focus of the video series is a quick revision on the principles of physiology of the autonomic nervous system, which is necessary for understanding the mechanism of action of drugs in this chapter.

What are the two divisions of the autonomic nervous system?

The two divisions of the autonomic nervous system are the sympathetic and parasympathetic systems.

What are the four elements discussed in relation to each system in the autonomic nervous system?

The four elements discussed are higher centers, nerves, chemical transmitters, and receptors.

What role do higher centers play in the autonomic nervous system?

Higher centers control all autonomic or visceral functions of the body and can be targeted by drugs to control the autonomic nervous system.

How do autonomic nerves differ from motor nerves in terms of their travel distance?

Autonomic nerves do not travel the whole distance as one segment. They first rely on a station called a ganglion, which regulates the strength of signals before reaching internal organs.

What is the main difference between the ganglia of the parasympathetic and sympathetic systems?

Parasympathetic ganglia are situated near the organs, while sympathetic ganglia are found very far from the organs and close to the spinal cord.

What neurotransmitter is released in both parasympathetic and sympathetic ganglia?

Acetylcholine is the neurotransmitter released in both parasympathetic and sympathetic ganglia.

What type of receptors does acetylcholine act on in ganglia?

Acetylcholine acts on nicotinic acetylcholine receptors in ganglia.

What are the main adrenergic receptors in the sympathetic system?

The main adrenergic receptors in the sympathetic system are alpha-1, alpha-2, beta-1, beta-2, and beta-3 receptors.

Why are ganglion blockers no longer used in controlling the autonomic nervous system?

Ganglion blockers are no longer used because they are non-selective and affect both sympathetic and parasympathetic ganglia, leading to depression of all autonomic functions throughout the body.

How can we selectively control the autonomic nervous system at the level of receptors?

We can selectively control the autonomic nervous system at the level of receptors by using drugs that target specific receptor subtypes, such as beta-1 blockers or alpha-1 blockers.

What happens to acetylcholine after it performs its function on the receptor?

After performing its function on the receptor, acetylcholine must be broken down immediately by choline esterase enzymes to prevent continuous stimulation.

What are the two types of choline esterase enzymes, and what are their roles?

The two types of choline esterase enzymes are true choline esterase (acetylcholine esterase), which specifically breaks down acetylcholine, and pseudocholine esterase (butyrylcholinesterase), which is non-specific and breaks down various choline esters, including some drugs.

What potential problem can arise in patients with pseudocholine esterase deficiency during surgery?

Patients with pseudocholine esterase deficiency can experience prolonged muscle paralysis and respiratory inhibition if given succinylcholine, a muscle relaxant, because the enzyme responsible for breaking down the drug is deficient.

Outlines

00:00

🧠 Introduction to the Autonomic Nervous System

This video introduces the principles of the autonomic nervous system (ANS) essential for understanding drug mechanisms in pharmacology. The ANS regulates visceral functions such as those of the heart and intestines, operating subconsciously. The ANS comprises the sympathetic and parasympathetic systems, each with four key elements: higher centers, nerves, chemical transmitters, and receptors. The video focuses on higher centers, nerves, and chemical transmitters, illustrating the brain, spinal cord, and control centers for autonomic functions.

05:02

❤️ Dual Nerve Supply to Organs

The heart is used as an example to explain the dual nerve supply from the sympathetic and parasympathetic systems. Most internal organs receive dual nerve supplies, although not always equally. Nerve signals from higher centers pass through the spinal cord to reach organs via nerve terminals. The video discusses ganglia as relay stations for autonomic nerves, situated near organs for the parasympathetic system and close to the spinal cord for the sympathetic system. These differences can be important in clinical scenarios.

10:04

⚡ Mechanisms of Neurotransmitter Release

The process of neurotransmission in the autonomic nervous system is described, highlighting how acetylcholine is released at ganglia and nerve terminals to activate receptors. The sympathetic system primarily releases norepinephrine, while the parasympathetic system releases acetylcholine at nerve endings. Receptor types are specified: muscarinic receptors (M1, M2, M3) for parasympathetic actions and adrenergic receptors (alpha-1, alpha-2, beta-1, beta-2, beta-3) for sympathetic actions. Each organ predominantly expresses certain receptor subtypes.

15:06

⚖️ Treating Autonomic Dysfunction

The video explains how to treat autonomic dysfunctions like tachycardia and bradycardia by targeting specific receptors. For example, beta-blockers can manage overactive sympathetic responses causing tachycardia, while drugs affecting M2 receptors can address bradycardia. This section summarizes the control of the autonomic nervous system at higher centers, ganglia, nerve endings, and receptors, with a preference for targeting receptors due to their selectivity.

20:06

🔬 Fate of Neurotransmitters

This section discusses the breakdown of neurotransmitters like acetylcholine by enzymes after their release and action. Two types of cholinesterase enzymes are described: true acetylcholinesterase, which specifically breaks down acetylcholine, and pseudocholinesterase, which also breaks down other substances like succinylcholine. The video highlights the significance of these enzymes in maintaining neurotransmitter balance and the implications of their inhibition or genetic deficiencies.

25:08

💉 Clinical Implications of Enzyme Deficiencies

The importance of cholinesterase enzymes is illustrated through the example of succinylcholine metabolism. A genetic deficiency in pseudocholinesterase can lead to prolonged muscle paralysis and respiratory issues during surgery. The video explains how anesthesiologists account for this enzyme's activity when dosing succinylcholine. This section emphasizes understanding enzyme functions and genetic variability for safe pharmacological interventions.

Keywords

💡Autonomic Nervous System

The autonomic nervous system (ANS) is a division of the nervous system that regulates involuntary functions such as heart rate, digestion, respiratory rate, and reflexes. It is divided into the sympathetic and parasympathetic systems. In the video, the ANS is described as controlling visceral functions and is fundamental for understanding pharmacology related to these systems.

💡Sympathetic Nervous System

The sympathetic nervous system is one division of the autonomic nervous system responsible for the 'fight or flight' response, increasing heart rate, and other functions that prepare the body for rapid action. The video discusses how sympathetic nerves originate from higher centers and transmit signals through ganglia to various organs, affecting functions like heart rate.

💡Parasympathetic Nervous System

The parasympathetic nervous system is the division of the autonomic nervous system responsible for 'rest and digest' activities, such as slowing the heart rate and promoting digestion. The video explains its role in involuntary control and its dual nerve supply to organs along with the sympathetic system.

💡Higher Centers

Higher centers refer to brain regions such as the medulla, hypothalamus, and cortex that regulate autonomic functions by sending signals through the spinal cord. The video highlights their role in controlling both sympathetic and parasympathetic systems and mentions that drugs can act on these centers to affect autonomic functions.

💡Ganglia

Ganglia are clusters of neuron cell bodies in the autonomic nervous system that act as relay stations, regulating signal strength before it reaches internal organs. The video differentiates between the ganglia locations in sympathetic (near the spinal cord) and parasympathetic (near the organs) systems, emphasizing their importance in signal transmission.

💡Acetylcholine

Acetylcholine is a neurotransmitter released by nerve endings in both the sympathetic and parasympathetic systems, responsible for transmitting signals across synapses. The video discusses its release and action on nicotinic acetylcholine receptors in ganglia, highlighting its crucial role in autonomic signaling.

💡Nicotinic Acetylcholine Receptor

Nicotinic acetylcholine receptors are ion channel receptors that respond to acetylcholine, causing depolarization and signal transmission in the autonomic nervous system. The video explains their fast response and importance in ganglionic signal relay, differentiating them from muscarinic receptors.

💡Norepinephrine

Norepinephrine, also known as noradrenaline, is a neurotransmitter released by sympathetic nerve endings, influencing functions such as heart rate and blood pressure. The video describes its release and action on adrenergic receptors, differentiating sympathetic responses from parasympathetic ones that use acetylcholine.

💡Adrenergic Receptors

Adrenergic receptors are receptors in the sympathetic nervous system that respond to norepinephrine and epinephrine, influencing various physiological responses. The video identifies different subtypes (alpha and beta receptors) and their roles in organs like the heart, emphasizing their significance in sympathetic signaling.

💡Cholinesterase Enzyme

Cholinesterase enzymes, including true (acetylcholinesterase) and pseudo (butyrylcholinesterase), break down acetylcholine after it performs its function. The video explains the critical role of these enzymes in terminating neurotransmitter activity and their significance in drug metabolism, highlighting differences in their specificity and locations.

Highlights

The autonomic nervous system (ANS) regulates all visceral functions without conscious control, including those of the intestines, lungs, and heart.

The ANS is divided into two systems: the sympathetic and the parasympathetic systems, each controlling different aspects of bodily functions.

Higher centers control autonomic functions through the brain, spinal cord, and nerve networks, which then regulate internal organs.

Sympathetic nerves (depicted in red) and parasympathetic nerves (depicted in black) originate from higher centers and control organ functions.

Most internal organs have a dual nerve supply from both sympathetic and parasympathetic systems, providing a balanced control mechanism.

Autonomic nerves rely on ganglia, which act as power stations to regulate signal strength before reaching internal organs.

Parasympathetic ganglia are located near organs, while sympathetic ganglia are situated close to the spinal cord, known as paravertebral ganglia.

Acetylcholine is a key neurotransmitter in the ANS, released at nerve terminals to activate receptors.

Parasympathetic nerve endings release acetylcholine, which acts on muscarinic receptors (M1, M2, M3) to regulate organ functions.

Sympathetic nerve endings release norepinephrine (noradrenaline), which acts on adrenergic receptors (alpha-1, alpha-2, beta-1, beta-2, beta-3).

Organs do not have all receptor types; instead, specific receptor subtypes predominate, such as M2 receptors in the heart for parasympathetic control.

The antagonistic function of sympathetic and parasympathetic systems ensures balanced control of organ functions, such as heart rate.

Autonomic dysfunctions, like tachycardia or bradycardia, can be treated by targeting specific receptors with drugs.

Drugs can control the ANS at higher centers, nerve endings, or receptors, with receptor-level control being the most selective and effective.

Acetylcholine must be rapidly broken down by enzymes (acetylcholinesterase or butyrylcholinesterase) after performing its function to prevent prolonged activation.

Butyrylcholinesterase, produced by the liver, is a non-specific enzyme that metabolizes various substances, including some drugs used in anesthesia.

Deficiency in butyrylcholinesterase can lead to prolonged effects of certain drugs, causing conditions like succinylcholine apnea during surgery.

Transcripts

hello everyone welcome to pharmacology

illustration series

we will specify this video and the next

one for a quick revision on principles

of physiology of the autonomic nervous

system

this is the background we need to be

able to understand the mechanism of

action of all drugs in this chapter

of course we don't need to explain all

principles of physiology however certain

points must be clarified to be able to

comprehend principles of pharmacology in

this chapter

first of all you should know that

autonomic nervous system is the division

of nervous system concerned with

regulation of autonomic function which

means all of visceral functions we have

as those of intestine lung heart or

whatever are not controlled of the

conscious level but are under control of

the autonomic nervous system which has

two divisions the sympathetic and the

parasympathetic systems and in each

system we need to discuss four elements

which are higher centers

nerves

chemical transmitters

and receptors

in this video we will explain the higher

centers nerves and chemical transmitters

seven receptors for discussion on the

next video now let's concentrate on this

drawing here

this is the brain the spinal cord and

here we have the higher centers

we will cover the sympathetic system

with red and the parasympathetic system

with black

these are the higher centers that

control all autonomic or visceral

function of the whole body when we say

higher centers we are talking about them

collectively to be more specific we have

centers here Omid Allah and centers

above and the hypothalamus above which

are centers in the articular information

and then we have centers in the cortex

centers in these levels are called

higher centers and now we can control

the autonomic function by drugs that act

on these centers

in this chapter we will have many drugs

which control the autonomic nervous

system by acting on these centers these

higher centers will send nerves passing

through spinal cord redkara is for

sympathetic nerves while black one has

four parasympathetic nerves

this autonomic nerve Supply will reach

any organ

so let's take the heart as an example of

the involuntary control of the autonomic

nervous system on such organs here you

see a dual nerve Supply composed of

sympathetic and parasympathetic nerve

fibers

and many but not all internal organs

have dual nerve supply of sympathetic

system and parasympathetic system nerve

fibers

to summarize

nerves is coming from higher centers

passing through the spinal cord until it

reach the internal organ and end with

what is known as nerve terminal and

those nerve terminals of sympathetic

system are different from those of the

parasympathetic system before discussing

how they are different from one another

you should know that autonomic nerves

don't travel the whole distance as one

segment like motor nerves do however

autonomic nerves must firstly rely on a

station

called ganglion which is composed of

collection of neurons

this ganglia act as a power station

regulating the strength of signals

before reaching the internal organs any

autonomic nerve must relay on ganglia

and in case of parasympathetic system

ganglia are situated near the organs but

in case of sympathetic system ganglia

are found very far from organs and close

to the spinal cord that's why it's

called

paravertebral gangly and this difference

is a rich source for questions an

examiner may put you through the

following scenario imagine if you were

in a lab and then we isolated a rabbit

heart and gave it to you and told you to

apply a certain medication on it now

tell me how can the drug affect the

isolated organ your answer as a student

will be like thus

the drug can act upon nerve terminals

either sympathetic or parasympathetic

and it can also act on a receptor and

that is reasonable because the Earth

terminals act by releasing transmitters

that activate receptors so the drug can

indeed act in a receptor

but if you say the drug can act on

ganglia here the examiner would ask you

to be more specific

and if you say sympathetic ganglia then

you have fallen into the examiner's

track when we isolate an organ it comes

with its parasympathetic ganglia only as

it is always situated close to the organ

side so when a drug is applied to an

isolated organ

it can act on a receptor nerve terminals

or parasympathetic ganglia specifically

now you may wonder if all internal

organs have dual Supply both systems the

answer is most but not all have dual

Supply however nerve supply of both

systems to an organ is rarely equal

sometimes the ratio of nerve Supply is

50 50 sometimes one system is given 80

percent of the autonomic nerves applied

to an organ while the other is only

contributing by 20 percent down to some

organ which have single supply of only

one system for example single

sympathetic nerve Supply is found in

superiorenal glands which is considered

as modified sympathetic ganglia sweat

gland also have only sympathetic nerve

Supply and most importantly the blood

vessels which are mostly supplied only

by sympathetic nervous system now you

know that most organs have dual nerve

Supply except accepting some organs

which have single Supply as mentioned

before

here we have talked about higher centers

which send fibers through spinal cord

given rise to nerves that Supply our

internal organs

and most of them have dual nerve Supply

but some has single Supply as those

mentioned before

now we need to look at the signal which

is generated in the higher centers then

it passes through the nerve till it

reached the ganglia where the signal in

the form of electrical depolarization

causes release of chemical transmitter

called acetylcholine

in this state

acetylcholine is termed neurotransmitter

then acetylcholine opens a gate inside

the ganglia this gate is considered as

receptor termed nicotinic acetylcholine

receptor

this type of receptor is Ion channel

receptor that will be discussed in the

next chapter of General pharmacology

you will know that this type of receptor

is the fastest one that can respond to

acetylcholine among all other types of

receptors

so now after the style cooling is

released inside the ganglia it opens a

gate named nicotinic acetylcholine

receptor causing sodium ion influx

causing depolarization that's because

during nerve transmission we need a fast

responding receptor type which has

nicotenica style choline receptor which

will generate another signal in the

post-ganglionic fibers in the form of

depolarization wave till it reach the

nerve endings again signals coming from

higher centers as depolarization wave

pulsing through nerves to reaching the

ganglia where it transforms from

electrical into chemical form

so the polarization wave releases

acetylcholine

acetylcholine opens a gate termed

nicotinic acetylcholine receptor when

this gate opens post ganglionic membrane

becomes depolarized and signals come in

this direction

so when pulsed ganglionic fibers are

depolarized the polarization wave

reaches nerve terminals then same

scenario will happen again as this

vesicles filled with acetylcholine where

rupture causing release of acetylcholine

which acts on its receptors present on

this organ now termed cholinergic

receptors and what are these cholinergic

receptors that are found in many organs

called it's called muscarinic receptors

and we have three well-known types of

muscarinic receptors termed in one M2

and M3 m is short for muscarinic and the

number is for the subtype so we have M1

M2 M3 and we also have M4 and M5 but

those two are of little significance

these are the mascarenic receptors which

will be discussed in detail but not

right now this whole system is called

parasympathetic system but what happens

in the sympathetic system

it is nearly the same as parasympathetic

system

higher centers send signals however

pre-ganglionic fibers and sympathetic

system are short as ganglia or situated

close to the spinal cord yet same

process occurs again as depolarization

wave reaches ganglia causing the release

of chemical transmitter which is also

the acetylcholine then acetylcholine

opens a gate called nicotinic

acetylcholine receptor

and when the gate opens it causes sodium

ion influx causing the polarization in

the post-synaptic membrane

then signal continue as depolarization

wave till it reach sympathetic nerve

endings however this time nerve endings

doesn't release

acetylcholine and instead it release

another transmitter termed

norepinephrine or noradrenaline and Tiny

amount of fibers release epinephrine but

most of them release norepinephrine

when vesicles rupture and release nor

adrenaline nor adrenaline acts on a

receptor so what do we call this

receptor

do we call it mascarenic cholinergic no

this time receptors are termed

adrenergic receptors

and what are adrenergic receptors we

have

we have five adrenergic receptors termed

alpha-1 Alpha 2 beta1 beta2 beta3

now I ask you do all internal organs

have all of these receptors

or that the heart has M1 M2 M3 alpha-1

Alpha 2 and so on of course not fans

tend to choose one or two receptors at

Max

for example chooses M2 when it

works under parasympathetic rule so that

we call M2 cardiac M2 receptors

that's because the heart doesn't have

much of M1 nor M3 but mainly M2

receptors

and same goes for sympathetic as most of

sympathetic receptors on the heart or of

beta1 subtype which predominates all the

other types others may be present like

alpha 1 Alpha 2 but they are of no

significance

beta1 receptor pre-dominates them all so

that we call it cardiac beta-1 receptor

to summarize all internal organs have

dual supply of sympathetic and

parasympathetic these two release

chemical transmitter that activates

receptors however organs don't have all

types of receptors and instead one of

each type predominates the other and

they always have antagonistic function

so if one is increasing the function

then the other one is decreasing it

now you may ask what is the benefit of

such antagonism this antagonism prevents

the organ from being controlled by only

one force

for example when one is activated

causing tachycardia the other one can

antagonize it and causes bradycardia but

where does the problem come from

a patient may come to you complaining of

tachycardia or rapid pulse now you

understand that this problem tachycardia

is caused by overactivity of sympathetic

system and this beta receptor is

overactive causing increased heart rate

so how can we treat this patient we can

give him a drug that either blocks this

beta receptor or activates the

antagonistic M2 which is able to

counteract the effect of beta receptor

on the contrary a patient may come to

you complaining of bradycardia so tell

me what's causing this problem yes it's

a parasympathetic system and we can give

him a drug either blocks M2 receptor or

activates beta receptors

so they can reach equilibrium

this background you now have enables you

to understand any autonomic malfunction

and how can you treat it

so can you tell me now what are the

methods of controlling the autonomic

nervous system first of all we can

control the autonomic nervous system at

the level of higher centers secondly we

can control the autonomic nervous system

at the level of ganglia either

sympathetic or parasympathetic ganglia

right we can control it by manipulating

the function of those ganglia

of autonomic nervous system can we

no we can't control the autonomic

nervous system at the level of ganglia

but why can't we control it at the level

of ganglia

it's because you already know that they

have the same chemical composition both

of them either sympathetic or

parasympathetic have the same chemical

transmitter acetylcholine and the same

receptor called nicotinic acetylcholine

receptor so a drug blocks acetylcholine

release is a non-specific drug as it

blocks both sympathetic and

parasympathetic ganglia

which leads to depression of all

autonomic function throughout the body

and this drug lacks a very important

quality which is not being selective

you can't Target acetylcholine or its

nicotenic receptor because in either way

you would be blocking both divisions of

the autonomic nervous system previously

there were drugs known as ganglion

blockers and others called ganglion

stimulants however these drugs are no

longer used due to lack of cell activity

so if an examiner asks you why ganglion

blockers are no longer used you can

simply answer because they are

non-selective and they act on Old

ganglia and thus we can't control their

effects

as such ganglion blockers would cause

depression of all autonomic ganglia

either sympathetic or parasympathetic

and this is a complex effect we do not

desire amidst now back to the original

question can we control autonomic

nervous system on the level of nerve

endings yes we can why because nerve

endings and parasympathetic system

release acetylcholine

button-sympathetic system they release a

different transmitter called nor

epinephrine here we can select one

Division and Target it with a drug acts

either on parasympathetic nerve endings

which release acetylcholine or

sympathetic nerve endings which release

norepinephrine so the second level we

can control autonomic function at as the

level of nerve endings thirdly and this

is the best option which is controlling

it at the level of receptors because

here I can choose even a subtype of

receptor from either divisions in this

chapter we will discuss a group of drugs

called beta-1 blockers that can block

beta1 receptors only orbital one and two

blockers or alpha-1 blockers and so on

and this is the best route being highly

selective so to summarize can we act on

higher centers

yes can we act on ganglia no

can we act on nerve endings yes

can we act on receptors yes and this is

the best route being highly selective

the next step after having understood

the function of nerve endings is the

fate of transmitters transmitters

released from ganglia as acetylcholine

or any other transmitter

we have to understand the fate of

transmitters to decide if it can be of

any value in the signs of pharmacology

now let's focus on this concept after

acetylcholine is released inside ganglia

either by sympathetic or parasympathetic

stimulation and perform a dysfunction on

the receptor

what happens to acetylcholine what is

the feet of acetylcholine you should

know that acetylcholine after performing

its function on the receptor must be

broken down immediately in a matter of

milliseconds

whether this acetylcholine is in the

ganglia or the nerve endings it's broken

down by the action of enzyme called

choline stress enzyme

this is the fate of acetylcholine after

performing its function on the receptor

we have two types of choline stress

enzyme

the fact is true and sudo are pretty old

now true is called

acetylcholine Strays and

pseudoculinistrace is called butyril

choline stress and the differences

between those two enzymes are of utmost

importance now we know that

acetylcholine after performing its

function it must be broken down by

either of two enzymes this through

choline stress is specific which means

it only breaks acetylcholine however

pseudo or butyril enzyme is non-specific

which means it doesn't break down only

acetylcholine but also other chemicals

are destroyed by this pseudo enzyme such

a as her win a well-known drug

it also breaks down procaine and

succinylcholine which will be discussed

later and is used as pre-anesthetic

medication used before surgical

operations as skeletal muscle relaxant

for induction of skeletal muscle

relaxation before surgical operations

this drug is used by anesthesiologists

in certain doses taken into

consideration that it is destroyed by

this enzyme called

sudokoline stress this is about

specificity but what about the site

since it's named true and it is specific

for acetylcholine then you can find it

in all vital areas such as ganglia

CNS and even red blood cells

but why does truecalline Strays present

in red blood cells do we actually have

acetylcholine in our red blood cells

this question will be answered later

however pseudo stress is produced by the

liver and thus you can find it in the

liver and is also present in plasma

again why the pseudoculinous trays

present in plasma do we have circulating

acetylcholine

this is the same question as the first

one however this question will be

answered now

do we have circulating a style choline

in our plasma no we don't have

acetylcholine circulating our bodies so

why do we have pseudoculinous trays in

plasma

the answer is because it is not specific

for acetylcholine so it's present in

plasma to break down many other

compounds such as heroin procaine

succinyl Cooling

even sometimes you may eat food that

contain choline Esters substance similar

to acetylcholine

and Zeus cooling Esters can enter our

blood-causing problems

that's why we need such enzyme in our

plasma and that's why it's sometimes

called biological scavenger

which means it can remove any cooling

Esters weather ingested or injected

now regarding the importance of both

enzymes

if I give you a drug blocks this choline

is Trace enzyme you die because it is

essential for life however this one is

not so much because it is not so

important in breaking down a style

cooling but for metabolism of other

drugs and regarding inhibition of both

enzymes two Strays required three months

to be regenerated again however sudo's

trees only need two weeks to be

regenerated again

okay here we need to lock on the

pseudoculines trace now you know that it

is needed for metabolism of other drugs

than acetyl cooling among these drugs

are succinylcholine a muscle relaxant

drug used before operation to induce

muscle relaxation but do you know some

people have genetic disease with the

gene responsible for pseudoculine stress

synthesis is not present

a child may be born and live his whole

life without knowing that he doesn't

have the gene responsible for cooling

stressed synthesis or the liver

synthesize abnormal form of the enzyme

I have told you this enzyme is not

essential for life

but when does the problem occur

this person can live without any problem

but if he have an operation where

succinylcholine is used the

anesthesiologists consider that 90

percent of this drug is metabolized in

circulation

so he must calculate the dose of

succinyl choline equals 90 percent of

this drug is metabolized before reaching

skeletal muscle so before obtaining the

desired effect on skeletal muscle 90

percent of the drug is eliminated by

pseudoculin stress enzyme so the amount

of drug that escapes the action of the

enzyme and reaches skeletal muscle to

produce its desired effect or only 10

percent of the given do's

now imagine if this child who inherited

a defective Gene from his parents and

didn't know this picture fact

went through an operation where the full

dose of succinyl cooling was

administered those 90 percent of the

Jews won't be metabolized and 100

percent of the those would reach the

muscles

causing not relaxation but muscle

paralysis

and this patient on operation Table

after administering sexy night cooling

to him would start to realize he can't

even breathe

and now he needs a ventilator in order

to survive until the tiny amount of

pseudoculin stress in his plasma can

metabolize and eliminate this drug this

is a fatal case of pseudoculine Strays

enzyme deficiency and because it leads

to respiratory inhibition it is

sometimes called sexy Nile cooling apnea

now I hope you understand the importance

of this background in order to be able

to understand the function of the

autonomic nervous system and how can we

interact with this function