Introduction to Local Anaesthesia

Dr. Rudraprasad Chakraborty1st year PG Student

Department of Oral & Maxillofacial SurgeryRama Dental college Hospital & Research Centre

Kanpur, UP

Inclusions…..

IntroductionPain PathwayNerve and Nerve conductionMode of Action of LAProperties of LAComposition of LAThe 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

One of the most commonly experienced symptoms .

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.

PAIN PATHWAY

…THE TRRIGEMINOTHALAMIC PATHWAY

3rd Ventricle

Left Thalamus

Right Thalamus

Pituitary

Anterior Nucleus

Medial

Nucleus

VLDL

Lateral nucleus

SUB DIVISIONS OF LATERAL NUCLEUS OF THALAMUS

VAL

VIL

VPL

VPM

DL

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 part1. The Peripheral Process2. The Axon3. 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 Nonmyelinated…………Tend to be blocked Last

In Unmyelinated Nerve : 35 per μmIn Myelinated Nerve/ at nodes : 20000 per μm

Sodium Channel on Nerve Membrane

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 fibers…………………Sympathetic A delta fibers………….Temperature sharp pain

Large Myelinated A alfa and beta fibers…..Motor and Proprioception

Small Unmyelinated C fibers……. ……………..Dull Pain

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 perineuriumEpineurium ….............Connective tissue supporting fasciculi and carrying nutrient vesselsEpineural sheath….…Outer layer of epineurium

Structure Description

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

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Acetylcholine was inolved in nerve membrane conduction & also it work as a neurotransmitter at nerve synapes.

ACETYL CHOLINE THEORY-

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

CALCIUM DISPLACEMENT THEORY-

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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

SURFACE CHARGE THEORY

Can not explain the activity of uncharged anesthetic

molecule in blocking nerve impulses ex-benzocaine

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MEMBRANE EXPANSION THEORYPreventing 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

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Most favored today.

Proposed that local anesthetics act by binding to specific receptors on the sodium channel.

SPECIFIC RECEPTOR THEORY

THE SODIUM CHANNELcomposed 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 (I–IV) each of which contains six protein segments (S1–S6).

THE ALPHA SUBUNIT OF THE SODIUM CHANNEL:

Sliding helix

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;

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) •Agent acting at receptor site on external surface of nerve membrane•Ex-Biotoxin

CLASS(B) •Agent acting at receptor site on internal surface of nerve membrane•Ex-quaternary ammonium analogues of lidocaine

CLASS(C) •Agent acting by a receptor-independent physicochemical mechanism•Ex-benzocaine

Class(D) •Combination of recepter&receptor independent mechanism•Ex-articaine,lidocaine, mepivacaine

OTHER METHODS OF CONTROLLING PAIN

Acupuncure Analgesia

Hypnotism

Audio Analgesia

Electric Anaesthesia/ Anelectrotonus

Anaesthesia by Cold Air

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.

HOW LA WORKS ?

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 blockadeCONDUCTION

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

Long Duration of Action

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:

Amide:

Procaine

Lidocaine

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 .

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Esters BA Ester

Butacaine Cocaine Piperocaine Tetracaine

PABA Ester Procaine Propoxycain

CLASSIFICATION OF LOCAL ANESTHESIA

Amides Bupivacaine Etidocaine Lidocaine Mepivacane

Quinoline Centbucridine

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 8.1Normal 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, Platelets and some parts of

GIT 2

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

Exposedshaftof hair

Sebaceousgland

Arrectorpilimuscle

Connectivetissue sheath

Root hairplexus

The Arrector Pili Muscle has Alpha 1 Stimulatory receptors

If Constricts

Goose Bump

Pupil : Dialator pupilae ( radial Muscle ) have Alpha 1 Stimulatory

Constriction makes Pupil to dialate

Respiratory System :

Needs more Air More Resp Rate

Dialation of Broncheoles needed

Broncheal Smooth Muscle Inhibition needed

(Beta 2 receptors)

BUT…. No Vasodialation Needed . Alpha 1 receptors stimulated in Blood

Vessels

Mast Cell

Histamine

Broncho constriction

Mast Cell has to be inhibited to keep potent airway

Beta 2 Receptors work over there

Respiratory System Cont..

Renal System : Alpha1 Stimulatory in Blood vessels

Decrease Blood Flow Decrease

Filtration

Less Urinary Output

• Beta 1 in Juxta Glomerular apparatus

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 ( Alpha 1)

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

Due to improper signaling to CNS, propermuscle tone is not maintained.

When Epinephrin goes up…

we feel TREMOR

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 1 1 2

Epinephrine 1 = 1 = 2

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

1 : 100000 1 : 200000

Norepinephrine : Normal patient : 0.34mg per

appointment i.e 34 ml of 1:100000 i.e 18 inj of 1.8ml

CVS patient : 0.14mg per appointment

i.e 14 ml of 1: 100000 i.e 7.7 injections of

1.8ml

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

Thanks