brief description about LA,its mechanism of action,nerve physiology,dose calculation

1. DEPARTMENT OF ORAL AND MAXILLOFACIAL
SURGERY
Seminar on
LOCAL
ANESTHESIA :
INTRODUCTION
COMPOSITION
MECHANISM OF ACTION
DOSE CALCULATION
Submitted by
Josna Thankachan
Final year part I
Al-Azhar Dental College

2. CONTENTS
• INTRODUCTION TO LOCAL ANESTHESIA
• PHYSIOLOGY OF THE PERIPHERAL NERVES
• ELECTROPHYSIOLOGY OF NERVE CONDUCTION
• ELECTROCHEMISTRY OF NERVE CONDUCTION
• IMPULSE PROPAGATION
• IMPULSE SPREAD
• MODE AND SITE OF ACTION OF LA
• WHERE DO LA WORK?
• HOW DOES LA WORKS?
• COMPOSITION OF LA
• PAIN
• METHODS OF PAIN CONTROL
• DOSE CALCULATION
• REFERENCES

3. INTRODUCTION TO LOCAL
ANESTHESIA
• DEFINITION
Local anesthesia is defined as the transient
and completely reversible 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.

4. Most desirable properties for a local anesthetic:
1. It should not be irritating to the tissue to which it is
applied.
2. It should not cause any permanent alteration of
nerve structure.
3. Its systemic toxicity should be low.
4. It must be effective regardless of whether it is
injected into the tissue or is applied locally to
mucous membranes.
5. The time of onset of anesthesia should be as short
as possible.
6. The duration of action must be long enough to
permit completion of the procedure yet not so long
as to require an extended recovery.

5. In addition to these qualities ,Bennat listed
other desirable properties of an ideal local
anesthetic:
7. It should have potency sufficient to give
complete anesthesia without the use of harmful
concentrated solutions.
8. It should be relatively free from producing allergic
reactions .
9. It should be stable in solution and should readily
undergo biotransformation in the body.
10. It should be sterile or capable of being sterilized
by heat without deterioration.

6. PHYSIOLOGY OF PERIPHERAL NERVES
The function of a nerve is to carry messages from one
part of the body to another . These messages in the
form of electrical action potentials, are called
impulses action potentials are transient
depolarizations of the membrane that result from a
brief increase in the permeability of the membrane
to the sodium, and usually also from a delayed
increase in its permeability to potassium. Impulses
are initiated by chemical, thermal,mechanical or
electrical stimuli.

7. Once an impulse is initiated by a stimulus in any
particular nerve fiber, the amplitude and shape of
that impulse remain constant without loosing
strength as it passes along the nerve because the
energy used for its propagation is derived from
energy that is released by the nerve fiber along its
length and not solely from the initial stimulus . And
thus is the impuse propagation along a nerve.

8. ELECTROPHYSIOLOGY OF NERVE
CONDUCTION
A nerve possesses a resting potential. This is a
negative electrical potential of -7O mV that
exists across the nerve membrane, produced
by differing concentrations of ions on either
side of the membrane.
The interior of the nerve is negative relative to
exterior.

9. • STEP 1: a stimulus excites the nerve leading to
the following sequence of events:-
– An initial phase of slow depolarization. The
electrical potential within the nerve becomes
slightly less negative.
– When the falling electrical potential reaches a
critical level, an extremely rapid phase of
depolarization results. This is termed as threshold
potential or firing threshold.

10. • This phase of rapid depolarization results in a
reversal of the electrical potential across the nerve
membrane . The interior of the nerve is now
electrically positive in relation to the exterior. An
electrical potential of +4O mV exists on the interior
of the nerve cell.

11. STEP 2:
After these steps of depolarization,
repolarization occurs. The electrical potential
gradually becomes more negative inside the
nerve cell relative to outside until the original
resting potential of -7Om V is again achieved .
The entire process requires 1 milli second;
depolarization takes O.3 msec; repolarization
takes O.7 msec.

12. Na+ ++++ ECF normal
k+ _ _ _ _ axoplasm -7OmV
resting potential
A Na+ ++++ B Firing
Step1,A&B K+ _ _ _ _ K+ -5O to -6OmV
slow depolarization
C Na+ _ _ _ _ to threshold potential
Step 1C ++++ potential +4OmV
rapid depolarization
++++
k+ ---- Repolarization
-6O to -9O mV

13. ELECTROCHEMISTRY OF NERVE
CONDUCTION
• Depends on :
• Concentration of electrolytes in the axoplasm and ECF
• The permeability of the nerve membrane to the sodium
and potasium ions
• Resting state:
In resting state ,the nerve membrane is
- Slightly permeable to sodium ions
- Freely permeable to pottasium ions
- Freely permeable to chloride ions

14. k⁺ remains within the axoplasm,despite the
ability to diffuse freely through the nerve
membrane and its concentration gradient.
Cl⁻ remains outside the nerve membrane
instead of moving along its concentration
gradient into the nerve cell.
Na⁺ migrates inwardly because both the
concentration and the electrostatic gradient
favours such migration.
The resting nerve membrane is relatively
impermeable to sodium prevents a massive
influx of this ion.

15. • Membrane excitation:-
Depolarization :- excitation of a nerve segment
leads to an increase in permeability of the cell
membrane to sodium ions. The rapid influx of
sodium ions to the interior of the nerve cell causes
depolarization of the nerve membrane from its
resting level to its firing threshold.

16. • Exposure of the nerve to a local anesthetic
raises its firing threshold.when the firing
threshold is reached,membrane permeability
to sodium ions increases dramatically and
sodium ions rapidly enter the axoplasm.
• At the end of depolarization,the electrical
potential of the nerve is actually reversed. The
entire depolarization process requires
approximately O.3 sec.

17. • Repolarization:-
The action potential is terminated when
the membrane repolarizes. This is caused by
the extinction of increased permeability to
sodium.
In many cells, permeability to pottasium
also increases, resulting in the efflux of
pottasium ions and leading to more rapid
membrane repolarization and return to its
resting potential.
The process of repolarization requires O.7
sec.

18. • Membrane channels:-

19. Discrete aqueous pores through the excitable
nerve membrane called sodium channels are
molecular structures that mediate its sodium
permeability.
The channel appears to be a lipoglycoprotein
firmly situated in the membrane. It consists of
an aqueous pore through which the ions
passes.

20. • The sodium ions pass through 12 times more
easily than pottasium ions. The channel
includes a portion that changes configuration
in response to changes in membrane
potential,thereby gating the passage of ions
through the pores.

21. • The presence of these channels helps to explain
membrane permeability or impermeability to
certain ions. Sodium channels have an internal
diameter of approximately O.3 ×O.5 nm.

22. • A sodium ion is thinner than a K⁺ or Cl⁻ ion
and therefore should diffuse freely down its
concentration gradient through membrane
channels into the nerve cell. However ,this
doesnot occur ,because all these ions attract
water molecules and thus become hydrated.

23. • Hydrated sodium ions have a radius have a
radius of 3.4 Å ,which is approximately 50%
greater than the 2.2 Å radius of pottasium and
chloride ions. Sodium ions therefore are too
large to pass through narrow channels when a
nerve is at rest. Pottasium and chloride ions
can pass through these channels.

24. • During depolarization ,sodium ions readily
pass through the nerve membrane because
configurational changes that develop within
the membrane produce transient widening of
these transmembrane channels to a size
adequate to allow the unhindered passage of
sodium ions down their concentration
gradient into the axoplasm.

25. Impulse propagation:-
After the initiation of action potential by a
stimulus,the impulse must move along the
surface of the axon.
The stimulus disrupts the resting equilibrium of
the nerve membrane; the transmembrane
potential is reversed momentarily with the
interior of the cell changing from negative to
positive,and the exterior changing from
positive to negative.

26. • This new electrical equilibrium in this segment
of nerve produces local currents that begin to
flow between the depolarized segment and
the adjacent resting area.

27. These local currents flow from positive to
negative,extending for several millileters along the
nerve membrane.
As a result of this current flow, the interior of the
adjacent area becomes less negative and its exterior
less positive. Transmembrane potential decreases,
approaching firing threshold for depolarization.
When transmembrane potential is decreased by 15mV
from resting potential a firing threshold is reached and
rapid depolarization occurs.
The newly depolarized segment sets up local currents in
adjacent resting membrane,and the entire process
starts new.

28. • Impulse spread:
the propagated nerve impulse travels along
the nerve membrane toward the CNS. The
spread of this impulse differs depending on
whether or not a nerve is myelinated.
Unmyelinated nerves:-
An unmyelinated nerve fiber has a high
electrical resistance cell membrane
surrounding a low resistance conducting core
of axoplasm ,all of which is bathed in low
resistance ECF.

29. The spread of an impulse in an unmyelinated
nerve fiber therefore is characterized by a
relatively slow forward creeping process. The
conduction rate in unmyelinated C fibers is 1.2
m/sec compared with14.8 to 120m/sec in
myelinated A- alpha and A- delta fibers.

30. Myelinated Nerves:
In myelinated nerves a layer of insulating material
separating the intracellular and extracellular
charges. The farther apart are the charges, the
smaller is the current needed to charge the
membrane.
Local currents thus can travel much farther in a
myelinated nerve than in an unmyelinated nerve
before becoming in capable of depolarizing the
nerve membrane ahead of it.

31. Impulse conduction in myelinated nerves occur
by means of curren leaps from one node to
node,a process termed as saltatory nerve
conduction . This form of impulse conduction
proves to be much faster and more energy
efficient than that employed in unmyelinated
nerves.

32. MECHANISM OF ACTION
• 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

33. WHERE DOES LA WORK??
Many theories have been promulgated to
explain the mechanism of action of LA…
• ACETYL CHOLINE THEORY
• CALCIUM DISPLACEMENT THEORY
• SURFACE CHARGE (REPULSION THEORY)
• MEMBRANE EXPANSION THEORY
• SPECIFIC RECEPTOR THEORY

34. ACETYL CHOLINE THEORY:
• This theory was proposed by Dett barn in the
year 1967.
• He stated that Acetyl choline was involved in
nerve conduction in addition to its role as
neurotransmitter at nerve synapses
• but there is no evidence that acetyl choline is
involved in neural transmission along the body
of the neuron

35. CALCIUMDISPLACEMENT THEORY:
• This theory was proposed by goldman in the
year 1966.
• He stated that local anesthetic nerve block is
produced by the displacement of calcium from
some membrane side that controlled
permeability to sodium
• But there is evidence that varying the
concentration of calcium ions bathing a nerve
does not affect local anesthetic potency.

36. SURFACE CHARGE REPULSION THEORY:
• This theory was proposed by Wei in the year
1969.
• He stated that local anesthetics bind to the nerve
membrane RNH+ (cationic) drug molecules were
aligned at the membrane–water interface and
because some of the LA molecules, carried a net
positive charge, they made the electric potential
at the membrane surface more positive, thus
decreasing the excitability of the nerve by
increasing the threshold potential.

37. • Evidence indicates the resting potential is
unaltered by LA, conveniently LA act within
the membrane channels rather than at the
membrane surface
• this theory cannot explain the activity of
uncharged anesthetic molecules
e.g.:Benzocaine

38. MEMBRANE EXPANSION theory…
• This theory was proposed by Lee in the year
1976.
• He stated that Local Anesthetic molecules
diffuse to hydrophilic regions of excitable
membranes, producing a general disturbance
of the bulk membrane structure, expanding
some critical region in the membrane and
preventing an increase in permeability to
sodium ions.

39. • Local anesthetic that is highly lipid soluble can
easily penetrate the lipid portion of the cell
membrane, producing a change in
configuration of the lipoprotein matrix of the
nerve membrane. This theory explains the
action of benzocaine which does not exist in
cationic form, yet still exhibit potent topical
anesthetic activity.

40. SPECIFIC RECEPTOR THEORY:
• This theory was proposed by Strichartz in the year
1987.
• He stated that local anesthetic acts by binding to
specific receptors on the sodium channel either on its
external surface or on the internal axoplasmic surface.
• Once access is gained to these receptors, permeability
to sodium ions is decreased or eliminated and nerve
conduction is interrupted.
• There are at least four sites within the sodium channel
at which drugs can alter nerve conduction

41. HOW LOCAL ANESTHETIC WORKS...
• Displacement of Ca ions from the sodium channel site,
which permits...
• Binding the LA molecule to this receptor site, which thus
produces...
• Blockade of the sodium channel, and a...
• Decrease in Na conductance, which leads to...
• Depression of the rate of electrical depolarization, and a ...
• Failure to achieve the threshold potential level, along with
a...
• Lack of development of propagated action potentials, which
is called...
• Conduction blockade.

42. All LA are available as acid salt of weak bases.
Weak base(BNHOH) combined with acid (HCL) to give acid
salt(BNHCL)& water.
In mucosa BNHCL dissociates into BNH and CL . Normal tissue
PH 7.4 is necessary for conversion of acid salt to free base.
BNH which is hydrophilic further dissociates to BN and H. BN
is now lipophilic.

43. – Lipophilic BN diffuses through nerve membrane (lipid).
Inside the nerve it combines with intrinsic H. (H in nerve
formed by buffering action.)
– Newly formed ionised BNH displaces calcium from the
sodium channel receptor site to cause conduction
blockade.

44. 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

47. • Nerve block produced by local anesthetics is
called as “non depolarizing nerve block”.
• The mechanism whereby sodium ions gain
entry to the axoplasm of the nerve ,thereby
initiating an action potential , is altered by
local anesthetics

48. COMPOSITION OF LA
COMPONENT
LIDOCAINE 2%
SODIUM CHLORIDE
STERILE WATER
VASOPRESSER( 1:1,OO,000 / 1:80,000)
Eg:- epinephrine,levonordefrin)
SODIUM METABISULFITE
METHYL PARABEN
FUNCION
LOCAL ANESTHETIC DRUG;BLOCKADE
OF NERVE CONDUCION
ISOTONICITY OF THE SOLUTION
VOLUME
↑ DEPTH AND ↑ DURATION OF
ANESTHESIA ; ↓ ABSORPTION OF LA
ANTIOXIDANT
BACTERIOSTATIC AGENT

49. LIGNOCAINE HYDROCHLORIDE
• Local anaesthetic agent
• pH of plain solution : 6.5
• pH of vasoconstrictor containing solution : 3.5
• Onset of action : rapid ( 3-5 minutes )
• Effective dental concentration : 2%

50. EPINEPHRINE (1:80,000 to 1:1,00,000)
• Added – to counteract vasodilation effect of
injectable L.A
– Decreases rate of absorption
– Decreases the risk of local anesthetic toxicity
– Increases duration of action
– Reduces bleeding at the site

51. SODIUM META BISULFITE
• Act as an antioxidant
• It prevent the oxidation of vasopressor by oxygen
• That is, sodium meta bisulphite react with oxygen
before the oxygen is able to destroy the
vasopressor
• When oxidised it becomes sodium bisulfate

52. METHYL PARABEN
• Commonly used in .1% concentration
• It is used as a preservative
•Possess bacteriostatic , fungistatic ,and antioxidant
properties .
•Repeated exposure to paraben has led to reports of
reports of increased allergic reaction

53. Sodium chloride
• Added to make the solution isotonic with the
tissues of the body

54. THYMOL
• It act as an antifungal agent
DISTILLED WATER
• It is used as the dilutant to provide the volume
of solution

55. PAIN
• Pain is defined as an unpleasant emotional
experience usually initiated by a noxious
stimulus and transmitted over a specialized
neural network to the central nervous system
where it is interpreted as such.

56. METHODS OF PAIN CONTROL
• Removing the cause
• Blocking the pathway of painful impulses
• Raising the pain threshold
• Preventing pain reaction by cortical depression
• Using psychosomatic methods

57. • Pain is divided into pain perception and pain
reaction.
• Any method of pain control will affect either
or both divisions.

58. Removing the cause:-
• Desirable method of controlling pain
• Environmental change in tissue should be
eliminated
• Consequently,free nerve endings would not be
excited and no impulses would be initiated.
• Affects pain perception

59. Blocking the pathway of painful
impulses:-
• Most widely used method in dentistry
• A suitable drug, possessing local anesthetic
properties ,is injected into the tissues in
proximity to the nerve or nerves involved.
• Interfere with pain perception

60. Raising the pain threshold:-
• Depends on pharmacological action of drugs
possessing analgesic properties.
• The drugs raise he pain threshold centrally
and therefore interfere with pain reaction.
• Pain perception is unaffected
• Pain reaction is decreased and thus pain
reaction threshold is raised.

61. Preventing pain reaction by cortical
depression:-
• Increasing depression of CNS by an anesthetic
agent prevents any conscious reaction to a
painful stimulus.

62. Using psychosomatic methods:-
• Neglected in dental practice
• Most important factor is honesty and sincerity
towards the patient.
• Inform the patient about the procedure and
what might be expected
• Reassure the patient
• Pain reaction is depressed and pain threshold
is inversely raised.

63. Dose calculation
• 2% lignocaine implies
2g/100 ml =2000mg/100ml = 20mg/ml
• 1:1000 soln of lignocaine with epinephrine means
1g/1000ml= 1000mg/ml =1mg/ml
• 1:100000= 1000mg/100000= 0.01mg/ml
• 1:80000= 1000mg/80000= 0.0125 mg/ml

64. • Maximum dose of LA without vasoconstrictor
=
4.4 mg/kg body weight
• Maximum dose of LA with vasoconstrictor =
6.6 mg/kg body weight

65. In a person with 70 kg body weight
• Maximum dose of LA without vasoconstrictor
=
300 mg
• Maximum dose of LA with vasoconstrictor =
500 mg

66. • As 1 ml of solution contains 20 mg of lidocaine
The amount of solution which contains maximum
dose of LA of 300mg without vasoconstrictor
=15 ml/solution
The amount of solution which contains maximum
dose of LA of 500mg with vasoconstrictor
=25 ml/solution

67. CARTRIDGE
• 1 cartridge =1.8 ml
• As 1ml contains 20 mg of lidocaine
• 1 cartridge contains =1.8 x 20
=36 mg of lidocaine

68. • No. of cartridge of maximum dose of LA
with
vasoconstrictor =500/36 = 13 cartridge
• No. of cartridge of maximum dose of LA
without
vasoconstrictor =300/36 = 9 cartridge

69. REFERENCE
• Handbook of LOCAL ANESTHESIA( 6th edition)
-Stanley F.Malamed
Monheim’s local anesthesia and pain control in
Dental practice(7th edition)
- Richard Bennett