Seminar on..

Local anesthesia- definition, neurophysiology and mode of

Moderator
Dr. Arun Kumar K.V.

Dr. Neeraja Singhla

Contents.

Introduction
Historical
background
Definition
Desirable
characteristic
Anatomic
consideration
Physiologic
considerations
Mode and site of
action of local
anesthetic
Kinetics of L.A.

Pharmacology of
LA.
Potentiation of
action of local
anestheticsvasoconstrictors
Recent advances
and future trends in
pain control
Chronic paincurrent modes of
treatment
Conclusion
References

Introduction

Historical background

1951, Pravez -hypodermic syringe.

1853, Alexander Wood -hollow metal needle.

COCAINE -first local anesthetic agent-isolated by

Nieman -1860 -from the leaves of the coca tree.

Its anesthetic action was demonstrated by Karl

Koller in 1884.

First effective and widely used synthetic local

anesthetic -PROCAINE -produced by Einhorn in
1905 from benzoic acid and diethyl amino ethanol.

Historical background

It anesthetic properties were identified by Biberfield

and the agent was introduced into clinical practice by
Braun.

LIDOCAINE- Lofgren in 1948.

The discovery of its anesthetic properties was

followed in 1949 by its clinical use by T. Gordh.

Thereafter, series of potent anesthetic soon followed

with a wide spectrum of clinical properties.

Definition

Local anesthesia

Local anesthetic agent

Various methods of inducing

local anesthesia

Mechanical trauma
Low temperature
Anoxia
Chemical irritants
Neurolytic agents such as a
alcohol and phenols
Chemical agents such as local
anesthetics.

Desirable characteristics
of local anesthesia .

Non irritating

Not cause any permanent alteration of nerve

structure

Low systemic toxicity

Must be effective regardless of whether it is

injected into the tissue or applied locally to
mucous membranes.

Short onset of anesthesia

Desirable characteristics
of local anesthesia .

Duration of action must be long

Potency sufficient to give complete

anesthesia without the use of harmful
concentrated solutions.

Free from producing allergic reactions

stable in solution and readily undergo

bio-transformation in the body.

Sterile

Anatomic

Structure of nerve fibers

Neuron
considerations
Sensory

Motor

Histochemistry

Schwann cells and myelin

Anatomy of a mixed nerve

Physiologic
considerations

Impulse action potential

Electrophysiology & electrochemistry of

nerve conduction

STEP- 1

INTRACELLULAR AND EXTRACELLULAR IONIC

CONCENTRATIONS
Ion

Intracellular
(MEQ/L)

Extracellular
(MEQ/L)

Ratio

Potassium (K+)

110-170

3-5

27:1

Sodium (Na+)

5-10

140

1:14

Chloride (Cl-)

5-10

110

1:11

STEP- 2

STEP - 3

Membrane
channels

IMPULSE PROPAGATION

IMPULSE SPREAD

Unmyelinated nerves

Myelinated nerves

Mode of action of
local anesthetic
local anesthetic agents interfere with excitation process in

a nerve membrane in one or more of the following ways:

Altering basic resting potential

Altering the threshold potential

Decreasing the rate of depolarization

Prolonging the rate of repolarization

Site - nerve membrane

Mechanism of action
RNHOH + HCl RNHCL + H2O
Weak strong
acid
water
Base
acid
salt

RNHCI RNH+ + CI-

RNH+ displaces calcium ions for the sodium channel receptor site.
which causes
Binding of the local anesthetic molecules to this receptor site
which produce
Blockade of sodium channel
and
Decrease in sodium conduction
which leads to
Depression of the rate of electrical depolarization
and
Failure to achieve the threshold potential level

Lack of development of propagated action potentials

called
Conduction blockade

Effect of pH

Acidic environment (low pH)

RNH+ > RN + H+

Basic environment (higher pH)

RNH+ < RN + H+

Henderson Hasselbalch equation

Log Base
Acid

pH pKa

Theories of mechanism
of action of L.A

Acetyl choline theory

Calcium displacement theory

Surface charge (repulsion) theory

Membrane expansion theory

Specific receptor theory

Acetyl choline theory

Calcium displacement theory

Surface charge (repulsion) theory

Membrane expansion theory

Specific receptor theory

Diffusion local
anesthetics

Reinjection of local anesthetic

Recurrence of immediate
propound anesthesia

Difficultly in re-achieving
profound anesthesia

Tachyphylaxis

Pharmacology of local
anesthetics

Differ from other drugs

Classification
Based on chemical structure
AMIDE

ESTER

benzoic acid

PABA

QUINOLINE

Based on biological site and mode of action

Class AClass BClass C Class D

Based on the source

Natural

Synthetic

Others

Based on mode of application

Topical

Injectable

Based on duration of action

Ultra short

Short

Medium

Long

Based on onset of action

Short

Intermediate

Long

Pharmacokinetics of
local anesthetics

Uptake

Oral route

Topical route

Injection

Metabolism

Esters

Amides

Excretion

Individual local
anesthetic agents
Drug

potency toxicity

pKa

Procaine

9.1

Propoxyc
aine

7-8

7-8

pH

Conc onset
used

life

5-6.5 2-4% 6-10

3.5min
5.5

hr

0.4% 2-3
min

Drug

potency toxicity

pKa

pH

Conc onset
used

life

Lidocaine

7.9

6.5
5-5.5

2%

2-3
min

1.6
hr

Mepivaca
ine

1.5-2

7.6

4.5
3-3.5

3%
2%

1.5-2
min

1.9
hr

Prilocaine

7.9

4.5
3-4

4%

2-4
min

1.6
hr

Drug

pKa

pH

Conc
used

7.8

4.45.2

4%

2-3
min

1.25
hrs

Bupivacai
4
<4
ne
(lidoc.) (lidoc.)

8.1

4.5-6 0.5% 6-10

3-4.5
min

2.7
hr

Etidocain
4
2
e
(lidoc.) (lidoc.)

7.7

4.5 1.5% 1.5 3

3-3.5
min

2.6
hr

Articaine

potency toxicity

onset life

Potentiation of action

ofVasoconstrictors
local anesthesia
pH alterations

Alkalinization

Carbonation

Potassium potentiation

Dextran prolongation

Oil solutions

Hyaluronidase

Miscellaneous

Dyes, acetylsalicylic acid, proteins etc.

Vasoconstrictors

Decrease blood flow

Lower anesthetic blood levels

Decrease the risk of toxicity

Increases duration of action

Decrease bleeding

Sympathomimetic drugs

Chemical structure
HO

C-C

HO

Classification
Catecholamines
Non catecholamines

Catecholamines

Non catecholamines

Epinephrine

Amphetamine

Nor-

Methamphetamine

epinephrine

Hydroxy-amphetamine

Ephedrine

Mephetermine

Dopamine
Levonordefrin
Isoproterenol

Adrenergic receptors

Ahlquist in 1948

Two types

Alpha () vasoconstriction

1 excitatory post synaptic

2 inhibitory post synaptic.

Beta () - vasodilation and bronchodilation + cardiac

stimulation

1 Found in heart & small intestines & responsible

for cardiac stimulation & lipolysis

2 found in bronchi, vascular beds, & uterus &

produces bronchodilation and vasodilation

Epinephrine

Most potent and widely used vasoconstrictor in

dentistry

Source: 80% of medullary secretion, also available as a

synthetic

Moa- both and , with being predominate

Systemic Effects of Epinephrine

Myocardium - heart rate & cardiac output

Pacemaker - risk of dysrhythmias

Coronary Artery-Dilation of coronary artery

B P- systolic pressure, effect on diastolic pressure is

dose related

Cardiovascular -Decrease cardiac efficiency

Vasculature
Vasoconstriction

in skin, mucous membrane

& kidneys
Vasodilation

in skeletal muscle in small

doses

Respiratory - Bronchodilator

CNS - Not a potent CNS stimulant

Metabolism
Increase

oxygen consumption

Glycogenolysis-

blood sugar

Termination of Epinephrine

Reuptake

COMT and MAO

Excreted unchanged in urine (1%)

Clinical Manifestations of Epinephrine Overdose

CNS stimulation - fear, anxiety, tremor, pallor, dizziness

Cardiac dysrhythmia

Ventricular fibrillation

Drastic increase in BP - can cause cerebral hemorrhage

Angina in patients with coronary insufficiency

Maximum Dose for Dental Appointment

Normal healthy patient

0.2 mg. per appointment

Significant cardiovascular impairment

0.04 mg per appointment

Clinical Applications for Epinephrine

Acute allergic reaction

Bronchospasm

Cardiac arrest

Hemostasis

Produce mydriasis

Vasoconstrictor

Norepinephrine

Dilutions of vasoconstrictors:
Dilution

Mg/ml

Therapeutic use

1:1,000

1.0

Emergency
medicine
(Im/Sc anaphylaxis)

1:2,500

0.4

Phenylephrine

1:10,000

0.1

Emergency medicine (IV

cardiac arrest)

1:20,000

0.05

Levonordefrin

1:30,000

0.033

Norepinephrine

1:50,000

0.02

Local anesthesia

1:80,000

0.0125

Local anesthesia

1:100,000

0.01

Local anesthesia

1:2000,000

0.005

Local anesthesia

Recent advances and future

trends in pain control

Centbucridine

quinalone derivative

five to eight times the potency of

lidocaine

Significantly is does not effect CNS

& CVS

Ropivacaine

long- acting amide anesthetic

prepared as a isomer

greater margin of safety

decreased cardio-toxicity

EMLA

pH alterations

Alkalinization - RN

Carbonation

Hyaluronidase

Ultra long acting local anesthetics

Tetradotoxin -puffer fish

saxitoxin -dinoflagelates.

Felypressin

Electronic dental anesthesia

TENS- 2Hz- tryptophan, serotonin & endorphins

Residual analgesic effect

Used in management of:

Causalgia
Phantom limb pain
Post herpetic neuralgia
Intractable cancer pain
Lower back pain
Ileus
Peripheral nerve injury
Bursitis
Parturition
Polycythemia vera
Cervical back pain
Post operative pain
Diabetic ulceration

EDA- 120 Hz or more- pain modulation

serotonin & endorphins- secondary role

Indications

TMJ/MPD (chronic pain)

Administration of local anesthesia

Acute pain

Nonsurgical periodontal procedure

Fixed prosthodontic procedures

Restorative dentistry

 Contraindications

Cardiac pacemakers
Neurological disorders
Status post cerebrovascular accident
History of transient ischemic attacks
History of epilepsy
Pregnancy
Immaturity (in ability to understand) the concept
of patient control of pain)
Very young pediatric patient
Older patients with senile dementia
Language communication difficulties

Advantages

No need for needle

No need for injection of drug
Patient is in control of the anesthesia
No residual anesthetic effect at the end of
procedure
Residual analgesic effect remain for several
hours

Disadvantages

Cost of the unit

Training
Learning curve initial success may
be low but will increase with
experience.
Intra oral electrodes weak link in the
entire system.

Chronic pain current

modes of treatment

Drug therapy

Anti-inflammatory and analgesic

Weak opioids

Strong opioids

Repeated local analgesic and

neurolytic blocks

Blocks of ANS

Cryoanalgesia

Radiofrequency heat lesion

Chemical hypophysectomy

Percutaneous cordotomy

Electro stimulation and

electrical non-invasive therapy

Acupuncture

Psychotherapy

Hypnosis

References

Principles of anesthesiology, 3rd edition, vol- 2, Vincent J.

Collins

Local anesthesia- mechanism of action and clinical useBenjamin G Cohino

Handbook of local anesthesia, 5th edition, Stanley F.

Malamed

Monehims local anesthesia and pain control, Benett

Current trends in pain research and therapy, Vol 4,

chronic pain reactions, mechanism and modes of
therapy

Local anesthesia- M. L. Kuzin

DCNA- Local anesthetics reviewed,46 (4), 2002

Internet references:

Google.com

Alta vista.com

Alltheweb.com

Canadian Journal of anesthesiology.org

Medvizion.net

Emedicine.net.

Thank you