Introduction to

Local Anaesthesia

Dr. Rudraprasad Chakraborty

1st year PG Student
Department of Oral & Maxillofacial Surgery
Rama Dental college Hospital & Research Centre
Kanpur, UP

Inclusions..
Introduction
Pain Pathway
Nerve and Nerve conduction
Mode of Action of LA
Properties of LA
Composition of LA
The Vasoconstrictors mainly used
with LA

A Doctor who can control pain and

give the patient relief from it, is the
Best Doctor for the Patient

INTRODUCTION

The first LA, cocaine, was isolated in 1860.

Cocaine introduced into practice in 1884 as a

topical ophthalmic anesthetic.

Despite its addictive property, cocaine was

used for 30 years.

In 1905 procaine was synthesized, which

became the dominant LA for the next 50 years.

Lidocaine, which is still a widely used LA, was

synthesized in 1943

PAIN
An unpleasant emotional experience usually
initiated by a noxious stimulus and
transmitted over a specialized neural
network to the CNS where it is Interpreted as
such.
One of the most commonly experienced
symptoms .

PAIN PATHWAY

THE TRRIGEMINOTHALAMIC PATHWAY

Left
Thalamus

3rd Ventricle

Pituitary
Right
Thalamus

Medial
s
Nucleu

DL

Anterior Nucleus
VL
Lateral nucleus

SUB DIVISIONS OF LATERAL NUCLEUS OF

THALAMUS

V
P
M

D
L

V
P
L

V
I
L

V
A
L

THE TRIGEMINOTHALAMIC TRACT

DISCRIMINATIVE TOUCH PATHWAY FROM HEAD

CONTROL OF PAIN
1.Removal of the cause
2.Blocking the pathways of pain
impulses
3.Raising the pain threshold
4.Preventing pain reaction by cortical
depression
5.Using psychosomatic methods

ANALGESIA, ANASTHESIA
ANALGESIA : Condition in which pain can not be
appreciated but the patient is aware of what is
happening.
ANAESTHESIA : Complete loss of all sensation
including that of Pain.

LOCAL ANAESTHESIA : Temporary loss of all

modalities of sensation in a limited region of the
body.

LOCAL ANAESTHESIA
Defined
as
reversible
and
transient loss of sensation in a
circumscribed area of the body,
caused
by
depression
of
excitation
in nerve endings or
inhibition of the conduction
process in peripheral nerves
Loss of sensation without inducing loss
of consciousness

THE NERVE/ THE NEURON

The Sensory neuron : Transmitting the
sensation of Pain
Consist three major part
1. The Peripheral Process
2. The Axon
3. The Cell Body

THE AXON

THE NERVE CONDUCTION

SODIUM CHANNEL TRANSITION

STAGES

DIFFERENTIAL CONDUCTION
BLOCKADE
A and B fibers are Myelinated.. Tend to
be
blocked
First
C fibers are NonmyelinatedTend to
be
blocked
Last

Sodium Channel on Nerve

Membrane

In Unmyelinated Nerve :
35 per m
In Myelinated Nerve/ at nodes : 20000 per m

IMPULSE SPREAD

In Myelinated Nerve, two to three

Nodes of Ranvier needed for
ensuring proper nerve block
At 0.5 to 3mm distance, there are
constrictions
That means, 8 to 10mm of Length
area of nerve is to be in contact
with LA

ORDER OF BLOCKADE
Smaller Myelinated
B fibersSympathetic
A delta
fibers.Temperature
sharp
pain
Large Myelinated
A alfa and beta fibers..Motor
and

Structure Description
Nerve fiber.... Single nerve
cell
Endoneurium Covers each nerve
fiber
Fasciculi ...Bundles of 500 to 1000 nerve
fibers
Perineurium .. Covers fasciculi
Perilemma .Innermost layer of
perineurium

SITE OF ACTION OF LA

Obviously The Nerve

Membrane

THE PERINEURIUM AND PERILEMMA

CONSTITUTE THE GREATEST ANATOMIC
BARRIERS TO DIFFUSION IN A
PERIPHERAL NERVE.

M = MANTLE, M= MOLAR/ C=CORE, C = CANINE

LA diffuses from periphery to centre of

the nerve
Mantle fibers are anaesthetised first
Core fibers are anaesthetised last
Recovery occurs at Reverse Direction

MODE OF ACTION OF LA
1.Altering the basic resting membrane
potential of nerve membrane
2.Altering the threshold potential ( Firing
Level )
3.Decreasing the rate of Depolarization
4.Prolonging the rate of repolarization

MECHANISM THEORIES
The acetylcholine Theory
The Calcium Displacement Theory
The Surface Charge ( repulsion )
Theory
The Membrane Expansion Theory
The Specific Receptor Theory

ACETYL CHOLINE THEORYAcetylcholine was inolved in nerve membrane conduction & also it work

CALCIUM DISPLACEMENT
THEORYNerve block was produced by the displacement of ca
from membrane site that control permeability to
sodium

33

SURFACE CHARGE THEORY

Local anesthesia acted by binding to the

nerve membrane & changing the electrical
potential at the membrane surface.

Decrease excitability of the nerve by

increase the threshold potential
Can not explain the activity
of uncharged anesthetic
molecule in blocking nerve
impulses ex-benzocaine

34

MEMBRANE EXPANSION THEORY

Preventing an increase permeability of sodium
LA are highly soluble to lipid & can easily penetrate
the lipid portion of cell membrane
Resulting decrease of sodium channel which lead to
an inhibition of both sodium conduction & neural
exicitation

35

SPECIFIC RECEPTOR THEORY

Most favored today.

Proposed that local anesthetics

act
by
binding
to
specific
receptors on the sodium channel.

36

THE SODIUM CHANNEL

composed of three subunits known as alpha,
beta1 and beta2
The pore through which sodium enters is
contained in the alpha subunit
The alpha subunit is made up of four similar
domains (IIV) each of which contains six
protein segments (S1S6).

THE ALPHA SUBUNIT OF THE SODIUM CHANNEL:

in the resting state with S4

segments in the body of the
channel;

In the firing configuration with

S4 segments in wall of the
channel;
Sliding helix

In the refractory
orientation with a protein
loop extended into the
channel

Exposure of binding site for

local anesthetics in segment
S6

Binding of LA maintaining
refractory orientation.

ACCORDING TO BIOLOGICAL SITE & MODE OF ACTION

CLASS(A)

OTHER METHODS OF CONTROLLING

PAIN
Acupuncure Analgesia
Hypnotism
Audio Analgesia
Electric Anaesthesia/
Anelectrotonus

HOW LA WORKS ?

Displacement of Ca++ from the sodium channel

receptor site. Which permits.

Binding of the local anesthetics molecules to this

receptor site. Which thus produces.

Blockade Of the sodium channel.

Decrease in sodium conductance which leads to

Depression of the rate of electrical depolarizatioN

Failure to achieve the threshold potential level along

with a.

Lack of development of propagated action potentials

which is called as ..

Conduction blockade

CONDUCTION
BOLCKADE

PROPERTIES OF LA
Non Irritating to the tissues
No Permanent Alteration in Nerve
Structures
Low Systemic Toxicity
Effective on tissue or mucous
membrane
Short Time of Onset

ADDITION OF BENETT
Potency without Harmful Concentrated
Solution
Free From Producing Allergy
Stable in Solution and Readily Undergo
Biotransformation
Should Be Sterile or capable of being
Sterilised without Deterioration

THE STRUCTURE OF LA

Ester: Procain
e

Amide: Lidocai
ne

PHYSICOCHEMICAL CHARACTERISTICS OF A
LOCAL ANAESTHETIC AFFECT ITS FUNCTION

The aromatic ring structure and hydrocarbon

chain length determine the lipid solubility of
the drug.

The more lipid soluble drug penetrates the cell

membrane more easily to exert its effect.

Thus bupivacaine which is highly lipid soluble

is approximately four times more potent than
lidocaine.

THE DURATION OF ACTION

Related to the length of the

intermediate chain joining the aromatic
and amine groups.

Protein binding , Procaine is only 6%

protein bound and has a very short
duration of action, wherease
bupivacaine is 95% protein bound.
bupivacaine have a longer duration of
action .

2/21/15

CLASSIFICATION OF LOCAL ANESTHESIA

Esters

BA Ester
Butacaine
Cocaine
Piperocaine
Tetracaine

PABA Ester
Procaine
Propoxycain

Amides
Bupivacaine
Etidocaine
Lidocaine
Mepivacane

Quinoline
Centbucridine

53

THE CHEMISTRY

LA Agents are weak base, unstable,

insoluble and UNIONIZED as FREE BASE
Mixing with Acid, Salt is produced
.Stable & soluble in water.

RN + H(+) RNH(+)+ RN

THE DISSOCIATION CONSTANT

The pKa : is the pH at which the Free
Base (RN) and Ionized cation ( RNH+)
are at equilibrium .
LA comes with pKa Value of 7.7 to 8.1
Normal Tissue pH : 7.4

LA UPON ALTERED TISSUE

ENVIRONMENT

pKa : 7.6

Tissue pH : 6.5
More Acidic
More H+ ions

More RNH(+). Less RN to enter

Axoplasm
LA will not work Properly

ESTERS

First group of LA to be developed

Short to Moderate duration of Action
( except
Tetracain)
Produces more vasodialation (Except
Cocain )

Pseudocholinesterase in blood metabolise it

End product PABA is highly allergic
Not used now a days

ATYPICAL PSEUDOCHOLINESTERASE

1:2800 ppl have this condition

Ester bond is not broken easily
Delayed metabolism
More Toxicity

AMIDES

Longer Duration of action

Causes less Vasodialation
Greater potency
Metabolised by Liver primarily
(prilocaine : Liver + Lung)
(Articaine: Liver + Blood )
Rarely Allergic

QUINOLINE

Centbucridine
4-N-butylamino-1,2,3,4-tetrahydro acridine
hydrochloride

Non Ester, Non Amide type L.A.

Study showes long action of Local
anaesthesia on human trial

ELEMINATION HALF LIFE

Rate of which LA is removed from blood

Time needed for 50% reduction = 1st

half life
for 75% reduction = 2nd
half life

COMPOSITION OF LA

LA itself
The Acid to Make it Stable
The Vasoconstrictor
The Antioxidant to make VC stable
The Preservatives
The Vehicle in the form of Normal
Saline
Nitrogen Bubbles to prevent O2
entrapement

Preservative: Stability of modern L.A is

maintained by adding Capryl hydro-

cuprienotoxin which includes

Xylotox and Methyl Paraben.

Reducing agent:
Act as preservatives for the vasoconstictor agents.
Vasoconstrictors are unstable in solution and may
oxidize,especially on exposure to prolonged sunlight.
Sodium metabisulphite which competes for the
available oxygen is added in the concentration
between 0.05% and 0.1%

Vehicle:The isotonic vehicle reduces discomfort

during injection.

VASOCONSTRICTOR

Sympathomimetic drugs
Acts on receptors which take
sympathetic mediators
and receptors
1 and 1 are stimulatory
2 and 2 are inhibitory

EPINEPHRIN AND NOR EPINEPHRIN

Stimulatory Receptors Maximum

1

Except : Heart 1
J.G. Apparatus 1
Lipocyte/
Adipocyte 3

Inhibitory Receptors Maximum 2

Except : Presynaptic Nerve Endings,

Coronary and Cerebral vasculature

have equal number of Alfa 1 and Beta
2, so not so much significant on
circulation of these two area

ACTION OF VC UPON DIFFERENT

AREA

Heart : Beta 1 ( Stimulatory) Present in

S.A. Node : +ve Chronotropic action
A.V. Node : +ve Dromotropic action
Purkinze Fibers : +ve Bathmotropic action
Ventricular Muscles : +ve Ionotropic action
.Resulting in Rise in Systolic BP

Skin : alpha 1 ( stimulatory) present in

Peripheral blood vessels smooth
muscles
Vasoconstriction
Increase in peripheral resistance
Rise in Diastolic BP

The Arrector Pili Muscle has Alpha 1

Stimulatory receptors

Exposed
shaft
of hair

Sebaceous
gland

Arrector
pili
muscle

Connective
tissue sheath

If Constricts
Goose
Bump

Root hair
plexus

Pupil :

Dialator pupilae ( radial

Muscle ) have Alpha 1 Stimulatory
Constriction makes Pupil to dialate

Respiratory System :
Needs more Air
Rate

More Resp

Dialation of Broncheoles needed

Broncheal Smooth Muscle Inhibition
needed
(Beta 2 receptors)
BUT. No Vasodialation Needed .

Respiratory System Cont..

Mast Cell

Histamine

Broncho constriction

Mast Cell has to be

inhibited to keep
potent airway
Beta 2 Receptors
work over there

Renal System :

Alpha1 Stimulatory in Blood

vessels

Decrease Blood Flow

Filtration

Decrease

Less Urinary
Beta
1 in Juxta Glomerular apparatus
Output

Stimulation of which increases fluid

retention in body
Rise in Blood Pressure

GIT :
Absorption and Secretory activity should
be decreased
Depends upon Mesenteric Blood Flow,
should have vasoconstriction ( Alpha 1)
Peristalsis should be
Inhibited
( Beta
2)
Pyloric and cecal
sphincture constricts

Effect on Na-K movement

Na-K ATPase takes back exhailed K+ ion

in.
Sensitive to Epinephrin by Alpha 1
Receptors
Hyperkaelimia does not occur

Effect on skeletal
muscle
When
Epinephrin
goes up
we feel
TREMOR

Due to improper signaling to CNS, proper

muscle tone is not maintained.

Effect on Endocrine system

More glucose is needed
Insuline should be less secreted
Pancreatic Beta Cells are Inhibited

Effect on Endocrine system

More glucose is needed
Insuline should be less secreted
Pancreatic Beta Cells are Inhibited
Alpha 2

Norepinephrine

Epinephrine

1 = 1 =

TERMINATION OF CATECHOLAMINES

C.O.M.T enzyme and M.A.O enzyme

act on both epinephrine and
norepinephrine.

COMT removes 3 and 4 hydroxyl

group
MAO removes carbon Hydroxyl group

End products are reuptaken by the

system

DOSE CALCULATION

Example 1: 100000 Adrenaline

1gram adrenaline in 100000ml of
solution
i.e 1000mg in 100000ml
i.e 0.01mg per ml solution
Preparation comes with 1 : 50000
1 : 80000

Norepinephrine :
Normal patient : 0.34mg per
appointment
i.e 34 ml of 1:100000
i.e 18 inj of 1.8ml
CVS patient :
appointment

0.14mg per
i.e 14 ml of 1: 100000

Epinephrine :
Maximum 0.2 mg , i.e 20ml of 1:
100000
Around 11 inj of 1.8 lakhs can be given

TO BE CONTINUED WITH

EMLA
Doses of LA
Techniques of LA
Complications of LA

Thank