LOCAL aNESTHESIA&

neurophysiology

Presented By,

N.SHEHLA AMINAFinal yr BDS

Local anesthesia has been defined as a loss of

sensation in a circumscribed area of the body caused

by a depression of excitation in nerve endings or an

inhibition of the conduction process in peripheral

nerves.

METHODS OF INDUCING LOCAL ANESTHESIA

Mechanical trauma

Low temperature

Anoxia

Chemical irritants

Neurolytic agents

Chemical agents - LA

DESIRABLE PROPERTIES OF LOCAL ANESTHESIA

Non irritating

Completely reversible

Low systemic toxicity

Effective topically & if injected

Time of onset – short

Adequate duration of action

Should give complete anesthesia w/o use of

harmful conc. solutions

Should not produce allergic reactions

Should be stable & readily undergo

biotransformation

Should be sterile or capable of being sterilized

FUNDAMENTALS OF IMPULSE GENERATION & TRANSMISSION

NERVE ANATOMY :

Neuron – structural unit of the nervous system.

Transmits messages b/w CNS & all parts of the

body.

Sensory and motor neuron

PARTS OF NEURON :

Dendritic zone

Axon

Cell body

AXOPLASMAXOLEMMA

EXTRACELLULAR FLUID

NERVE PHYSIOLOGY :

Stimuli

Impulse

Amplitude & shape -constant

Resting potential

Slow depolarization

Rapid depolarization

ELECTROPHYSIOLOGY :

Repolarization

RESTING POTENTIAL :Negative electric potential of -70 mV

Na+ + + + + ECF

K+

STEP 1 : ( 0.3 msec )•Slow depolarization•Threshold potential or firing threshold – 50 to – 60 mV•Rapid depolarization + 40 mV

+ + + +

STEP 2 : ( 0.7 msec )•Repolarization•Reaches – 70 mV

ELECTROCHEMISTRY :Depends onConc. Of electrolytes in the axoplasm & ECFPermeability to Na+ & K+

RESTING STATE :Slightly permeable to Na+Freely permeable to K+ & Cl-MEMBRANE EXCITATION :Depolarization : ExcitationIncreased permeability to Na+Transient widening – passage of Na+Decrease of 15 mV necessary to reach firing threshold - initiate impulse ( - 50 to -60 mV )Na+ permeability increases.Electrical potential reversed

DEPOLARIZATION :Absolute refractory period - lasts for duration of axnpotentialRelative refractory period – new impulse initiated ( stronger stimuli )

REPOLARIZATION :Action potential terminatedInactivation / extinction of permeability of Na+Permeability to K+ increases – efflux of K+Rapid membrane repolarization ( - 70 mV )

AFTER REACHING RESTING STATE :Excess Na+ in axoplasmExcess K+ ECFEnergy provided by oxidative metabolism of ATP.

Where do local anesthetics work ?Nerve membrane is the site at which local anesthesia exert their

pharmacological actions

THEORIES TO EXPLAIN THE MECHANISM OF AXN :Acetyl choline theory ACh – a neurotransmitter ,was involved in nerve

conduction at nerve synapse.

No evidence that Ach is involved in neural transmission

along the body of neuron.

Calcium displacement theory Displacement of calcium from some membrane site that

controlled permeability to Na.

Varying the conc. of Ca does not affect the potency of LA

– hence credibility of this theory diminished

Surface charge (repulsion) theory

LA binds to nerve membrane & changes the electrical

potential at membrane surface.

Cationic drug molecules – LA molecules net positive

charge – EP positive

Increases threshold potential

Decreases excitability of nerve

Resting potential – unaltered & LA act within the

membrane.

Cannot explain activity of uncharged molecules

Membrane expansion theory LA diffuse – hydrophobic regions – general disturbance of

membrane structure – prevents inc. in permeability to Na+

LA –highly lipid soluble – penetrates – lipid portion.

Change in configuration – decreased diameter of Na

channel

Inhibition of Na conduction & neural excitation

No direc evidence tat nerve conduction is entirely blocked

Specific receptor theory Specific receptor site for LA exist in Na channel ( either

on externel or internal surface )

LA binds to these specific receptor

Permeability of Na decreases

Interruption in nerve conduction

Calcium – bound form within nerve membrane –

regulating role for movement of sodium

Release of bound calcium – primary factor – increased Na

permeability.

LA molecule act by competitive antagonism with calcium

Nerve membrane – polarized state

Ionic movements fail to develop

Membrane’s electrical potential – unchanged

Local currents do not develop.

Impulse arriving at blocked nerve segment – stopped

Unable to release energy for continued propagation

Nerve block produced by LA - NONDEPOLARIZING

NERVE BLOCK

How do local anesthetics work

Displacement of Ca+ from sodium channel receptor site

Binding of LA to this receptor site

Blockade of sodium channel

Decrease in sodium conductance

Depression of rate of electrical depolarization

Failure to achieve threshold potential

Lack of development of propagated axn potential

CONDUCTION BLOCKADE

SPECIAL NOTE

Why LA does not work in an area of

inflammation & infection ?

RNH+ RN + H+

At lower pH,concentration of H+ increases

At higher pH , concentration of H+ decreases

RNH+ > RN + H+

RNH+ < RN + H+

Proportion of ionic forms depend on pKa.pKa = pH ,then 50 % - 50 %% of drug calculated by Henderson- Hasselbalch eqn.

Log Base/Acid = pH - pKa

RNH+ RN + H+

RNH+RN

Na channel

INFECTION / INFLAMMATION : pH = 6Dec. pH ,RNH+ inc.

Inc. vascularity causes inc. absorption into blood vessels.Adeqate blockade not possible because only a small amt of base form cross the nerve sheath and increased absorption into dilated blood vessels.

DOSE CALCULATION

Maximum permissible dose of lignocaine = 4.4 mg/kg body wt

Maximum permissible dose of lignocaine = 7 mg/kg body wt

with adrenaline

Concentration of lignocaine = 2 % = 20 mg/ml

1 ml = 1/20 mg

Example : for 70 kg patient

Maximum permissible dose of lignocaine = 4.4 * 70 = 308 mg

= 15.4 ml

Maximum permissible dose of lignocaine = 7 * 70 = 490 mg

with adrenaline = 24.5ml

Maximum permissible dose of adrenaline = 0.2/0.0125

= 16 ml

Maximum permissible dose of adrenaline = 0.04 /0.0125

in cardiovascular patients = 3.2 ml

1 : 80,000 dilution of adrenaline = 1 gm of adrenaline

in 80,000 ml of

solvent1000 mg/ml = 0.0125 mg/ml 80000

1 ml = 1/0.0125 mg

Maximum permissible dose of adrenaline = 0.2 mg/appt.

Maximum permissible dose of adrenaline = 0.04 mg/appt.

in cardiovascular patients