Pharmacology - Local Anaesthetic

Summary

This video offers an insightful overview of local anesthetics, their use in minor surgeries, and their mechanism of action on nerve fibers. It explains how local anesthetics, like lidocaine and bupivacaine, penetrate the cell membrane to block sodium channels, preventing pain signals from reaching the brain. The video also touches on the history of anesthetics, mentioning cocaine as the first discovered, and discusses side effects and the unique properties of tetrodotoxin from pufferfish. It concludes with a look at different types of local anesthetics, their applications, and potential risks.

Takeaways

• 😲 Local anesthetics are used to numb a small part of the body during minor surgery.
• 🌿 Cocaine was one of the first local anesthetics discovered and is still used today.
• 💊 The effectiveness of local anesthetics depends on their form; in an ionized form, they cannot penetrate the cell membrane.
• 🔬 Local anesthetics work by penetrating the cell membrane in an un-ionized form and then ionizing inside the neuron to block sodium channels, preventing nerve impulse propagation.
• 🚫 Local anesthetics are more effective on smaller nerve fibers and particularly on myelinated fibers.
• 🐡 Tetrodotoxin (TTX), a natural toxin secreted by pufferfish, also blocks sodium channels but from the outside, unlike common local anesthetics.
• 💡 Lidocaine, also known as 'League no pain', is a commonly used local anesthetic with rapid induction and medium duration, often used in dentistry.
• 🚨 Side effects of local anesthetics can include headache, dizziness, confusion, and potentially fatal CNS depression.
• 💔 Local anesthetics can also affect the heart, causing myocardial depression and vasodilation.
• 🛑 Bupivacaine is used for long surgeries due to its long duration but requires caution due to high cardio toxicity.
• 👍 The video provides a brief but informative overview of local anesthetics, their mechanisms, and their clinical applications.

Q & A

What are local anesthetics used for in medical procedures?

Local anesthetics are used to numb a small part of the body during minor surgery, preventing the sensation of pain in the area where they are administered.

Who discovered cocaine as an anesthetic and what is its significance?

Cocaine was one of the first anesthetics discovered and was the first ester-type local anesthetic. It has historical significance as a milestone in the development of local anesthetics.

How does the form of a drug affect its ability to be absorbed by the body?

A drug in its unionized form can penetrate the cell membrane and be absorbed by the body, whereas a drug in its ionized, polar form cannot penetrate the cell membrane and is less effective.

What is the pKa of a typical local anesthetic and how does it relate to its effectiveness?

A typical local anesthetic has a pKa of about 8 and 9. In its unionized form, it can penetrate the cell membrane and is quite effective. However, at physiological pH, which is slightly acidic, it becomes ionized and less able to penetrate the cell membrane.

How do local anesthetics work to numb an area?

Local anesthetics work by penetrating the cell membrane of nerve cells, becoming ionized inside, and binding to sodium channels, thus preventing the influx of sodium ions and blocking the propagation of nerve impulses, which numbs the area.

Why are local anesthetics more effective on smaller nerve fibers?

Local anesthetics are more effective on smaller nerve fibers because they are more susceptible to the blocking action of the anesthetic compared to larger fibers.

What is the difference between tetrodotoxin (TTX) from pufferfish and local anesthetics used in hospitals?

Tetrodotoxin (TTX) blocks the sodium channel from the outside, preventing sodium ions from entering the neuron and stopping the action potential. In contrast, local anesthetics used in hospitals typically block the sodium channel from the inside of the neuron.

What are some common side effects of using local anesthetics?

Side effects of using local anesthetics can include headache, dizziness, confusion, and CNS depression, which can be fatal if it leads to respiratory depression.

How does cocaine differ from other local anesthetics in terms of side effects on the heart?

Unlike other local anesthetics, cocaine does not cause myocardial depression but instead increases heart activity, which can lead to different cardiovascular effects.

What are some popular types of local anesthetics mentioned in the script?

Some popular types of local anesthetics mentioned are lidocaine (known as 'League no pain' in some regions), which is used for its rapid induction and medium duration, and bupivacaine, which has a slow onset, long duration, and medium tissue penetration but is associated with high cardio toxicity.

Why is care needed when using bupivacaine as a local anesthetic?

Care must be taken when using bupivacaine because it has high cardio toxicity, making it necessary to monitor patients, especially those with heart conditions, to avoid complications.

Outlines

00:00

🩺 Overview of Local Anesthetics

In this video, we explore the basics of local anesthetics, which are used in minor surgeries to numb specific body parts. We discuss the importance of the drug's ionization state for effectiveness, the use of cocaine as the first anesthetic, and how local anesthetics work by blocking nerve signals to the brain. The video covers the concept of local anesthetics being weak bases with a pKa of about 8-9, which penetrate cell membranes in their un-ionized form but become ineffective in acidic environments.

05:00

⚖️ How Local Anesthetics Work

This section explains the mechanism of local anesthetics, detailing how they numb specific body parts by targeting nerve fibers, particularly pain fibers. Local anesthetics block sodium channels inside neurons, preventing the transmission of pain signals to the brain. The video also highlights the susceptibility of different nerve fibers to local anesthetics, noting that smaller, myelinated fibers are more affected than larger ones. The segment concludes with a brief mention of tetrodotoxin (TTX) from pufferfish, which blocks sodium channels from the outside.

Keywords

💡Local Anesthetics

Local anesthetics are drugs that cause a reversible loss of sensation in a specific area of the body. They are used in minor surgeries to numb a small part of the body, allowing procedures to be performed without the patient feeling pain. In the script, the use of local anesthetics is exemplified by a doctor injecting the substance to numb an area before a procedure.

💡Cocaine

Cocaine is mentioned as one of the first anesthetics discovered and is historically significant in the development of local anesthetics. It is used in the script to illustrate the evolution of anesthetics and to contrast with modern anesthetics in terms of safety and side effects.

💡pKa

pKa stands for the acid dissociation constant and is a measure of the acidity or basicity of a substance. In the context of local anesthetics, a weak base with a pKa of about 8 and 9 can penetrate the cell membrane in its un-ionized form, which is crucial for its effectiveness. The script explains how the physiological pH can affect the ionization state of local anesthetics, impacting their ability to numb an area.

💡Cell Membrane

The cell membrane is a selectively permeable barrier that controls the movement of substances in and out of cells. The script discusses how local anesthetics, being weak bases, can penetrate the cell membrane in their un-ionized form but become ionized and ineffective when they encounter the slightly acidic physiological pH inside the cell.

💡Nerves

Nerves are essential for transmitting signals between different parts of the body. Local anesthetics work by blocking the transmission of pain signals along nerve fibers, particularly the afferent pain fibers, as explained in the script. This prevents the brain from receiving the pain signals, resulting in numbness.

💡Action Potential

An action potential is an electrical signal that travels along nerve cells, allowing for communication between the body's parts. The script describes how local anesthetics prevent the generation and conduction of nerve action potentials by blocking sodium channels, which is key to their numbing effect.

💡Sodium Channels

Sodium channels are protein structures in the cell membrane that allow the passage of sodium ions, which is crucial for the generation of action potentials. The script explains that local anesthetics block these channels from the inside, preventing the influx of sodium ions and thus stopping the propagation of action potentials.

💡Tetrodotoxin (TTX)

Tetrodotoxin, or TTX, is a naturally occurring toxin found in pufferfish that is lethal to humans. Unlike local anesthetics used in medicine, TTX blocks sodium channels from the outside, preventing the action potential from passing through. The script uses TTX as an example to contrast with medical local anesthetics.

💡Lidocaine

Lidocaine, also known as lignocaine, is a popular local anesthetic known for its rapid onset and medium duration. It is commonly used in dentistry due to its good tissue penetration. The script mentions it as an example of a widely used local anesthetic and also notes its secondary use as an anti-arrhythmic drug.

💡Bupivacaine

Bupivacaine is a local anesthetic with a slow onset, long duration, and medium tissue penetration, making it suitable for long surgeries. However, the script warns of its high cardiotoxicity, indicating that caution is needed when using it, especially in patients with heart conditions.

💡Side Effects

Side effects are unintended consequences of using a drug. The script discusses common side effects of local anesthetics, such as headache, dizziness, confusion, and CNS depression, which can be severe or even fatal. It also contrasts these with the stimulating effects of cocaine, which does not cause CNS depression but can increase heart activity.

Highlights

Local anesthetics are used to numb a small part of the body for minor surgery.

Cocaine was one of the first local anesthetics discovered.

Local anesthetics can be administered through various methods including intra-dermal, subcutaneous, or in the spine.

The effectiveness of a drug depends on its form; non-ionized forms can penetrate the cell membrane.

Local anesthetics are weak bases with a pKa of about 8 and 9, becoming ionized in physiological pH.

Local anesthetics work by blocking sodium channels, preventing the generation and conduction of nerve action potential.

Tetrodotoxin (TTX), a natural local anesthetic from pufferfish, blocks sodium channels from the outside.

Side effects of local anesthetics include headache, dizziness, confusion, and CNS depression.

Cocaine does not cause CNS depression but instead causes excitement.

Local anesthetics can also affect the heart, leading to myocardial depression and vasodilation.

Lidocaine, also known as 'League no pain', is commonly used in dentistry and has anti-arrhythmic properties.

Propofol, another local anesthetic, has many side effects and is not very useful.

Bupivacaine has a slow onset, long duration, and medium tissue penetration, making it suitable for long surgeries.

Bupivacaine has high cardio toxicity and requires caution in patients with heart conditions.

Local anesthetics generally work more on smaller nerve fibers due to their susceptibility.

Local anesthetics are more effective on myelinated nerve fibers than unmyelinated ones.

The video provides a brief but comprehensive overview of local anesthetics and their applications.

Transcripts

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here you can also shoot on to questions

or some interesting things including

ours you can also change the Chloe

settings to the highest one for better

graphics in this video we're going to

look at local and aesthetics and this is

sort of an overview on local

anaesthetics to do with pharmacology now

local anesthetics are used in minor

surgery to numb a small part of the body

so here you can see some doctor in

injecting some local anesthetics into

the body to numb the area so we can't

feel anything

interestingly cocaine was one of the

first anesthetics actually it was the

first itis type to be discovered we can

administer at aesthetics through intra

dermal subcutaneous or in tropical in

the spine before we continue on please

remember the basics of pharmacology if a

drug is an onion eyes form it can

penetrate the cell membrane it is

effective for example it can be absorbed

by the body however if a drug is in an

ionized form if it's polar it cannot

penetrate the cell membrane it's not

very effective and for example it cannot

be absorbed by the body now a local

anesthetic is a weak base with a pKa of

about 8 and 9 and in an unannounced form

it can penetrate the cell membrane it is

quite effective however if when it

enters a physiological pH which is

slightly acidic below 7 it will become

ionized and so it cannot penetrate the

cell membrane so for example if we were

to administer a local anesthetic to a

person suffering from high levels of

acids in their body the local anesthetic

will be ionized very quickly and so is

not

very effective so this is an important

concept to know and will I will learn

more about it during this video so how

do local anesthetic works will they numb

a small part of the body by particularly

working on the nerves especially the

African air fibers the pain fibers by

preventing the pain fibers to send pain

signals to the brain let's have a closer

look here is the cell membrane of the

neuron with channels here is the outside

of the neuron and here is the inside the

insides not going to be here it's meant

to be in the inside I hope you

understand that in the inside of the

neuron it's more negatively charged in

respect to the outside in the inside we

have more potassium ions and in the

outside we have more sodium ions when an

action potential or impulse travels

through along the neuron the inside will

become more positive like so because of

the influx of sodium ions from the

outside to the inside what happens when

a local anesthetic comes along a local

anesthetic will come along in an onion

eyes form meaning that it can penetrate

the cell membrane so here the local

anesthetic will penetrate the cell

membrane and come inside the neuron the

inside of the neuron is slightly acidic

in the physiological pH and so when this

local anesthetic goes inside the neuron

it will become ionized and so will not

leave this the neuron and this is what

we want because then the local

anesthetic in an onion and I announced

form can bind on the sodium channels

here and essentially prevent the sodium

ions from coming inside the neuron and

so prevent the impulse or action

potential from propagating down along

the neuron so in summary a local

anesthetic

essentially prevents both the generation

and conduction of the nerve action

potential it blocks the sodium channels

by physically plugging the transmembrane

port from the inside and so when we

prevent the conduction of this action

potential from this pain fiber that

means that the brain will not receive

this pain signal and so we would we

would feel no pain when we use local

anesthetics however local anesthetics

actually work on every type of nerve not

only these afferent nerve fibers the

pain fibers but as a general rule they

work more on smaller fibers because

small fibers are more susceptible than

large fibers and local anesthetics also

work particularly on myelinated more

than unmyelinated nerve fibers so if we

draw this up from the most susceptible

to the least susceptible is that

nociceptors the pain fibers are more

susceptible to local anesthetics and

then we have the sympathetic fibers the

temprature fibers and and so on and so

on

until finally on motor fibers but we

would need a massive dose of local

anesthetic to paralyze a person as a

side note let's look at another type of

local anesthetic a natural one which is

secreted by pufferfish and it's a toxin

so here again I'm drawing a membrane of

a neuron and with the channel the inside

is more negative and respect to the

outside but when an action potential

comes along the inside will become more

positive the pufferfish as we know is

pretty toxic for humans and that is why

we stay away from it the pufferfish this

is because the pufferfish secretes a

toxin known as tetrodotoxin or TTX TTX

unlike our local anesthetic that we use

in hospital TTX blocked the sodium

channel from the outside like so and so

this will not allow sodium ions to come

inside and so will not allow the

action potential to pass through the

side effects of using local anesthetic

include headache dizziness confusion and

CNS depression which may be fatal if it

leads to respiratory depression

however cocaine actually doesn't cause

CNS depression but causes excitement

instead so that's cocaine

side effects of local anesthetic also

affect the heart it can lead to

myocardial depression vasodilation as

well and so care must be taken we have

to check the blood pressure before

giving local anesthetic cocaine again on

the other hand doesn't cause myocardial

depression but increases like the

activity now let's look at some types of

local anesthetics some popular ones

League no pain also called lidocaine in

America is as a rapid induction has a

medium duration so you won't feel pain

for medium duration has good tissue

penetration and it's very commonly used

especially in dentistry I think but

lignin can also works as an

anti-arrhythmic drug a class 1 B so this

league no pain can be a local anesthetic

as well as anti-arrhythmic drug as an

anti-arrhythmic drug it tries to are fix

not fixed but tries to help in

arrhythmias so it works on the

depolarization phase rapid

depolarization phase of the ventricles

so if this was the normal action

potential of a ventricle myocyte where

we in the zero phase we have a rapid

depolarization caused by an increase in

sodium influx lignum cane will cause

this type of shift which will

essentially deep slow down the

depolarization phase but we don't really

need to know that leg McCain is a

antiarrhythmic drug because this is a

local anesthetic video but that's just a

good concept

to understand another type of local

anesthetic is propane which is I wrote

here crap because it has many side

effects and it's not very useful and the

last look like I said I will talk about

is bupivacaine it has a slow onset a

long duration and medium tissue

penetration so it's pretty good and that

is why it is commonly used in long

surgeries because of this long duration

however it has high cardio toxicity so

care must be taken when using this with

people suffering from my heart failure

or something like that I hope you

enjoyed this video on local anaesthetic

it was very brief but please like share

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