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PROPERTIES
&
MECHANISM OF LOCAL ANESTHETICS
DR.SIDDHARTH DHANARAJ
ORAL & MAXILLOFACIAL SURGEON
DEFINITION
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 in
peripheral nerves.
An important feature of local anesthesia is
that it produces : loss of sensation without
producing loss of consciousness
Definition :
Drugs that cause reversible loss of sensory
perception specially of pain in a restricted
area of the body, when applied topically or
local injection.
LA if applied to a mixed nervesensory and
motor impulses are interruptedresulting in
muscular paralysis and loss of autonomic
control.
Action of local
anesthetic
The concept
They prevent both
the generation and
the conduction of a
nerve impulse.
It sets up a chemical
roadblock between
the source of impulse
(e.g. the scalpel
incision in soft
tissues) and the
Historicalbackground
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.
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PROPERTIESOFLOCAL
ANESTHESIA
I==It should not be irritating to tissue to which it
is applied
N==It should not cause any permanent alteration
of nerve structure
S==Its systemic toxicity should be low
T==Time of onset of anesthesia should be short
E== It should be effective regardless of whether
it is injected into the tissue or applied locally to
mucous membranes
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D==The duration of action
should be long
ELETROPHYSIOLOGYOF
NERVECONDUCTION
ActionPotentials
At rest: Na+& K+ channels closed. -70mV
Fibre stimulated: Na+channel opens, Na+ enters
cell. Potential rising
Cell depolarised, Na+ channel closes. +20mV
K+ channel opens, K+ exits cell, potential falling
Fibre repolarised, Na+& K+ channels closed. Na/K
pump restores balance. -70mV
Result is a voltage gradient along axon, causing a
current. This causes configurational change in Nachannels in the next segmentconduction
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SLOWDEPOLARIRIZATION
RAPIDDEPOLARIZATION:
TheinteriorofnerveisPOSITIVEinrelationtoexterior.
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REPOLARIZATION:
.
SODIUM PUMP
energy comes from the
oxidative metabolism of ATP
Depolarization takes 0.3 msec
Repolarization takes 0.7 msec
The
MYLINATEDNERVES:
Impulse conduction in myelinated nerves occurs
by means of current leaps from nodes to node
this process is called as SALTATORY
CONDUCTION.
It is more rapid in thicker nerves because of
increase in thickness of myelin sheath and
increase in distance between adjacent NODES
OF RANVIER.
If conduction of impulse is blocked at one node
the local current will skip over that node and
prove adequate to raise that membrane
potential at next node to its firing potential and
produce depolarization.
Conduction rate of myelinated fibers is 120m/sec.
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IMPULSEPROPOGATION
IMPULSE SPREAD
The propagated impulse travels along the nerve
membrane towards CNS. The spread of impulse
differs in myelinated and unmyelinated nerve fibers.
THEORIESMECHANISMOF
ACTIONOFLOCALANESTHETICS
Many theories have been promulgated
over the years to explain the mechanism
of action of local anesthetics.
ACETYLECHOLINE THEORY: Stated that
acetylcholine was involved in nerve
conduction in addition to its role as a
neurotransmitter at nerve synapses.
There is no evidence that acetylcholine is
involved in neural transmission.
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CALCIUMDISPLACEMENTTHEORY:
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SURFACECHARGE(REPULSION)THEORY:
Proposed that local anesthetic acted by binding to nerve
membrane and changing the electrical potential at the
membrane surface. Cationic drug molecule were aligned at
the membrane water interface, and since some of the local
anesthetic molecule carried a net positive charge, they
made the electrical potential at the membrane surface
more positive, thus decreasing the excitability of
nerve by increasing the threshold potential. Current
evidence indicate that resting potential of nerve
membrane is unaltered by local
anesthetic.
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MEMBRANEEXPANSIONTHEORY
MEMBRANEEXPANSIONTHEORY
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SPECIFICRECEPTORTHEORY:
CLASSIFICATIONOFLOCALANESTHETIC
SUBSTANCESACCORDINGTOBIOLOGICALSITE
ANDMODEOFACTION
CLASS A: Agents acting at receptor site on external
surface of nerve membrane
Chemical substance: Biotoxins (e.g., tetrodotoxin and
saxitoxin)
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SYNTHETIC
OTHERS
BASED ON MODE OF APPLICATION
INJECTABLE
TOPICAL
BASED ON DURATION OF ACTION
ULTRA SHORT
SHORT
INTERMEDIATE
LONG
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Local anesthetics
Esters
Esters of
benzoic
acid
Butacaine
Cocaine
Benzocaine
Hedylcaine
Piperocain
e
Tetracaine.
Esters of
paraaminobenzoic
acid
Chloroprocain
e
Procaine
propoxycaine
Amides
Articaine
Bupivacain
e
Dibucaine
Etidocaine
Lidocaine
Mepivacain
e
prilocaine
Quinoline
centbucridine
Differences
ESTERS
Short duration of action
Less intense analgesia
Higher risk of hypersensitivity
ESTER linked LA s are rarely
used.
Hydrolyzed by Plasma
Cholinesterase in blood.
Rarely used for Infiltration
anesthesia
But useful for topical ana on
mucous membranes.
AM IDE S
Produce more intense and
longer lasting ana.
Bind to alpha1 acid
glycoprotein in plasma
Not hydrolyzed by Plasma
Cholinesterase, but in liver
DISSOCIATIONOFLOCALANESTHETICS
Local anesthetics are available as salts (usually
hydrochlorides) for clinical use.
The salts, both water soluble and stable, is
dissolved in either sterile water or saline.
In this solution it exists simultaneously as
unchanged molecule (RN), also called base and
positively charged molecules (RNH+) called cations.
RNH+ <34 RN + H+
base/acid = pH - pKa
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36
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MODEANDSITEOFACTIONOF
LOCALANESTHETICS
Local anesthetic agent interferes with excitation
process in a nerve membrane in one of the
following ways:
MECHANISMOFACTIONOFLOCAL
ANESTHETICS
The following sequence is proposed mechanism of
action of LA:
Conduction blockade
40
Na + Na +
Na + Na +
THE
CARTRIDGE
Components of the
Cartridge
Syringe
Components
1.) Needle adapter
2.) Piston with
harpoon
3.) Syringe barrel
4.) Finger grip
5.) Thumb ring
49
50
Needle
The Needle Gauge: the larger the gauge the
smaller the internal diameter of the needle
Usual dental needle gauges are 25,27, & 30
Length:
1-Long(approximately 40 mm "32-40 mm"), for
NB.
2-Short(20-25 mm).
3-Extra-short(approximately 15 mm), for PDL.
51
Componentsofneedle
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COMERCIALLYPREPAREDLOCALANESTHESIA
CONSISTSOF:
53
REDUCINGAGENT
Vasoconstrictors are unstable in solution and
may oxidize especially on prolong exposure to
sunlight this results in turning of the solution
brown and this discoloration is an indication
that such a solution must be discarded.
To overcome this problem a small quantity of
sodium metabisulphite is added - competes
for the available oxygen.
SHELF LIFE INCREASES
54
PRESERVATIVE
Modern local anesthetic solution are very
stable and often have a shelf of two years
or more. Their sterility is maintained by the
inclusion of small amount of a preservative
such as capryl hydrocuprienotoxin.
Some preservative such as methylparaben
have been shown to allergic reaction in
sensitized subjects.
55
FUNGICIDE
In the past some solutions tended to
become cloudy due to the proliferation of
minute fungi.
56
VEHICLE
The anesthetic agent and the additives
referred to above are dissolved in distilled
water & sodium chloride.
This isotonic solution minimizes discomfort
during injection.
57
Cartridge Contents
Example:
2% lidocaine in a cartridge
(1.7ml)
2% = 20mg/ml
and we have 1.7ml so
20 mg/ml
X 1.7 ml= 34 mg
this means we have 34mg of lidocaine in a cartridge
ans: 51mg
Dilution of
Vasoconstrictors
Questions:
1:100,000 dilution.... whats the concentration in (mg/ml)
Again, 1 here mean 1000mg
PHARMACOKINETICSOFLOCAL
UPTAKE:
ANESTHETICS
61
METABOLISM(BIOTRANSFORMATION)
ESTER LOCAL ANESTHETICS:
Ester local anesthetics are hydrolyzed in the plasma by the enzyme pseudocholinesterase.
Chloroprocaine the most rapidly hydrolyzed, is the least toxic.
Tertracaine hydrolyzed 16 times more slowly than Chloroprocaine ,hence it has the greatest potential
toxicity
.
62
AMIDELOCALANESTHETICS
63
EXCRETION
Kidneys are the primary excretory organs for both the local
anesthetic and its metabolites
A percentage of given dose of local anesthetic drug is
excreted unchanged in the urine.
Esters appear in only very small concentration as the parent
compound in urine.
Procaine appears in the urine as PABA (90%) and 2%
unchanged.
10% of cocaine dose is found in the urine unchanged.
Amides are present in the urine as a parent compound in a
greater percentage then are esters.
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Mepivacaine
on a patient.
Mepivacaine
Indication:
When vasoconstrictor is NOT indicated
Most often used in pediatric / geriatric patient
Types
3% without vasoconstrictor (MCG: Carbocaine)
2% with vasoconstrictor ( Levonodefrin )
Types of
Vasoconstrictors
Natural catecholamines
Epinephrine
Norepinephrine
Dopamine
Synthetic catecholamines
Isoproterenol
Levonordefrin
Non-catecholamines
Amphetamine,
Ephedrine,Methamphetamine
REFERENCES
HANDBOOK OF LOCAL ANESTHESIABY STANLEY F.MALAMED. 6TH EDTN.
LOCAL ANESTHESIA IN DENTISTRY
J.A.BAART & H.S.BRAND.