DR.SID-LA YR3.pptx

7/21/2019 DR.SID-LA YR3.pptx

http://slidepdf.com/reader/full/drsid-la-yr3pptx 1/68

COMPOSITION

PROPERTIES&MECHANISM OF LOCAL ANESTHETICS

DR.SIDDHARTH DHANARAJORAL & MAXILLOFACIAL SURGEON



DEFINITION

Local anesthesia has beendefned as a loss o sensation ina circumscribed area o the bodycaused by a depression oexcitation in nerve endings in peripheral nerves.

An important feature of local anesthesia isthat it produces : loss of sensation withoutproducing 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 nerve—sensory and

motor impulses are interrupted—resulting in

muscular paralysis and loss of autonomiccontrol.



Action of local

anet!etic

T!e conce"t

T!e# "$e%ent ot!t!e 'ene$ation an(t!e con()ction of a

ne$%e i*")le.

It et )" a c!e*ical

$oa(loc+ et,eent!e o)$ce of i*")le

-e.'. t!e cal"elinciion in oft

ti)e an( t!e









Historical background

COCAINE -rst local anesthetic agent-isolated

by Nieman -!"# -from the lea$es of the coca

tree.

Its anesthetic action was demonstrated by

%arl %oller in !!&.

'irst e(ecti$e and widely used synthetic local

anesthetic -)*OCAINE -produced by Einhorn in

+#, from benoic acid and diethyl amino

ethanol.

8



9

•It anesthetic properties were identied by ibereld

and the agent was introduced into clinical practice by

raun.

•/I0OCAINE- /ofgren in +&!.

• 1he disco$ery of its anesthetic properties was followed

in +&+ by its clinical use by 1. 2ordh



PROPERTIES OF LOCAL

ANESTHESIA

I33It should not be i$$itatin' to tissue to which itis applied

N33It should not cause any permanent alteration

of ne$%e structure

433Its #te*ic to5icity should be low

133Ti*e of onet of anesthesia should be short

E33 It should be e/ecti%e regardless of whetherit is in6ected into the tissue or applied locally tomucous membranes

0331he ()$ation of action should be long10



00

It should ha$e the potency su7cient to gi$e complete

anesthesia with out the use of harmful concentrationsolutions

It should be free from producing allergic reactions

It should be free in solution and relati$ely undergo

biotransformation in the body

It should be either sterile or be capable of being

sterilied by heat with out deterioration.



ELETROPHYSIOLOGY OF

NERVE CONDUCTION 1here is an electrical charge across the membrane.

1his is the membrane potential.

1he resting potential 8when the cell is not ring9 is anegati$e electrical potential of -#m$ that e5ists

across the ner$e membrane; produced by di(erent

concentrations of either side of the membrane.

1he interior of ner$e is NE2A1I<E in relation to e5terior.

12



Action Potentials

At rest: Na=> %= channels closed. -#m<

'ibre stimulated: Na=channel opens; Na= enterscell. )otential rising

Cell depolarised; Na= channel closes. =?#m<

%= channel opens; %= e5its cell; potential falling

'ibre repolarised; Na=> %= channels closed. Na@%

pump restores balance. -#m< *esult is a $oltage gradient along a5on; causing a

current. 1his causes congurational change in Na-channels in the ne5t segmentconduction

01



SLOW DEPOLARIRIZATION

02

RAPID DEPOLARIZATION:

The interior of nerve is POSITIVE in relation to exterior.



REPOLARIZATION:

.

15

• 0epolariation taes #.B msec

• *epolariation taes #. msec

4O0ID )D)energy comes from theo5idati$e metabolism of A1)

• 1he entire process reuire msec



MYLINATED NERVES:

Impulse conduction in myelinated ner$es occurs

by means of current leaps from nodes to nodethis process is called as SALTATOR3CONDUCTION.

It is more rapid in thicer ner$es because ofincrease in thicness of myelin sheath and

increase in distance between ad6acent NODESOF RAN4IER.

If conduction of impulse is bloced at one nodethe local current will sip o$er that node and

pro$e adeuate to raise that membranepotential at ne5t node to its ring potential andproduce depolariation.

Conduction rate of myelinated bers is ?#m@sec.

16





What about Myelinated Nerve Fibers ?

A-α and A-deltaup to 120

m/sec

!iber is 1"2 m/sec

onduction rate comparison



IMPULSE PROPOGATION

IMPULSE SPREAD

1he propagated impulse tra$els along the ner$emembrane towards CN4. 1he spread of impulsedi(ers in myelinated and unmyelinated ner$e bers.

UNM3ELINATED NER4ES5 1he high resistance cellmembrane and e5tra cellular media produce a rapiddecrease in density of current with in a shortdistance of depolaried segment.

1he spread of the impulse is characteried as a lo,

fo$,a$(6c$ee"in' "$oce.



THEORIES MECHANISM OF

ACTION OF LOCAL ANESTHETICS

Dany theories ha$e been promulgatedo$er the years to e5plain the mechanismof action of local anesthetics.

ACET3LECHOLINE THEOR3 : 4tated thatacetylcholine was in$ol$ed in ner$econduction in addition to its role as aneurotransmitter at ner$e synapses.

1here is no e$idence that acetylcholine isin$ol$ed in neural transmission.

20



CALCIUM DISPLACEMENT THEORY:

4tates that local anesthetic ner$e bloc was produced

by displacement of calcium from some membrane sitethat controlled permeability of sodium.

21



SURFACE CHARGE (REPULSION) THEORY:

)roposed that local anesthetic acted by binding to ner$e

membrane and c!an'in' t!e elect$ical "otential 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 positi$e charge; they

made the electrical potential at the membrane surface

more positi$e; thus (ec$eain' t!e e7citailit# ofne$%e # inc$eain' t!e t!$e!ol( "otential. Current

e$idence indicate that resting potential of ner$e

membrane is unaltered by local anesthetic.22



MEMBRANE EXPANSION THEORY It states that local anesthetic molecule di(use to

!#($o"!oic $e'ion of e7citale *e*$ane;

producing a general disturbance of bul membrane

structure; e5panding membrane; and thus pre$enting

an increase in permeability to sodium ions. /ipid

soluble /A can easily penetrate the lipid portion of cell

membrane changing the conguration of lipoprotein

matri5 of ner$e membrane. 1his results in decreased

diameter of sodium channel; which leads to inhibition

of sodium conduction and neural e5citation.

23



MEMBRANE EXPANSION THEORY

82



SPECIFIC RECEPTOR THEORY: 1he most fa$ored today; proposed that local

anesthetics act by binding to specic receptors on

sodium channel the action of the drug is direct; not

mediated by some change in general properties of

cell membrane. iochemical and electrophysiological

studies ha$e indicated that specic receptor sites for

local anesthetic agents e5ists in sodium channel

either on its e5ternal surface or on internal

a5oplasmic surface. Once the /A has gained access to

receptors; permeability to sodium ion is decreased or

eliminated and ner$e conduction is interrupted.25



CLASSIFICATION OF LOCAL ANESTHETIC

SUBSTANCES ACCORDING TO BIOLOGICAL SITE

AND MODE OF ACTION

CLASS A: Agents acting at receptor site on e5ternal

surface of ner$e membrane

Chemical substance: ioto5ins 8e.g.; tetrodoto5in andsa5ito5in9

CLASS B: Agents acting on receptor sites on internal

surface of ner$e membrane

Chemical substance: Fuaternary ammonium analogues

of lidocaine; scorpion $enom26



CLASS C: Agents acting by receptor independent ofphysiochemical mechanism

Chemical substance: enocaine

CLASS D: Agents acting by combination of receptorsand receptor independent mechanisms

Chemical substance: most clinically useful anestheticagents 8e.g.; lidocaine; mepi$acaine; prilocaine9

27



A4E0 ON 1GE 4O*CE NA1A/

4HN1GE1IC

O1GE*4

A4E0 ON DO0E O' A))/ICA1ION

• INEC1A/E

• 1O)ICA/

• A4E0 ON 0*A1ION O' AC1ION

• /1*A 4GO*1

• 4GO*1

• IN1E*DE0IA1E

• /ON2 28



Local anet!etic

Ete$

Ete$ ofen9oic

aci(

:)tacaine

Cocaine

:en9ocaineHe(#lcaine

Pi"e$ocaine

Tet$acaine.

Ete$ of"a$a6

a*inoen9oicaci(

C!lo$o"$ocain

eP$ocaine

"$o"o7#caine

A*i(e

A$ticaine

:)"i%acaine

Di)caine

Eti(ocaine

Li(ocaine

Me"i%acaine

"$ilocaine

;)inoline

cent)c$i(ine



If the local anesthetic has two JiKs

in its nameL itMs an amide

/idocaine)rilocaine

upi$acaineArticaine

Depi$acaine



Dierences

E S T E R S Short duration of action

Less intense analgesia

Higher risk of hypersensitivity ESTER linked LA s are rarely

used.

Hydrolyzed by Plasa

!holinesterase in blood. Rarely used for "nfiltration

anesthesia

#ut useful for topical ana on

ucous ebranes.

A ! D " #

$roduce more intense and

longer lasting ana.

%ind to alpha& acid glycoprotein in plasma

'ot hydroly(ed by $lasma

)holinesterase, but in liver

*arely cause hypersensitivity

reactions+ no cross reactivity

with "#"* L A s.



$rug should reach %erve through tissue

$rug should enter %euron & %erve ' Hydrophilic

Lipophilic



DISSOCIATION OF LOCAL ANESTHETICS

/ocal anesthetics are a$ailable as salts 8usuallyhydrochlorides9 for clinical use.

1he salts; both water soluble and stable; is

dissol$ed in either sterile water or saline. In this solution it e5ists simultaneously as

unchanged molecule 8*N9; also called base andpositi$ely charged molecules 8*NG=9 called cations.

RNH< ==== RN< H<

33



1he relati$e concentration of each ionic form in thesolution $aries in the pG of the solution or surroundingtissue.

In the presence of high concentration of hydrogen ion8low pG9 the euilibrium shifts to left and most of theanesthetic solution e5ists in cationic form.

RNH< > RN< < H<

As hydrogen ion concentration decreases 8higher pG9the euilibrium shifts towards the free base form.

RNH< ? RN < H<34



1he relati$e proportion of ionic form also depends on p%a or0I44OCIA1ION CON41AN1; of the specic local anesthetic.

1he p%a is a measure of molecules a7nity for G= ions.

hen the pG of the solution has the same $alue as p%a of the localanesthetic; e5actly half the drug will e5ists in the *NG= form ande5actly half in *N form.

1he percentage of drug e5isting in either form can be determined byGenderson Gasselbalch euation

Lo' ae@aci( = "H 6 "a

35



Hen(e$on !aelac! eB)ation 0etermineshow much of a local anesthetic will be in a non-ionied $s ionied form . ased on tissue pG andanesthetic )a .

In6ectable local anesthetics are wea bases8pa3.,-+.,9 hen a local anesthetic isin6ected into tissue it is neutralied and part ofthe ionied form is con$erted to non-ionied 1he

non-ionied base is what di(uses into the ner$e.

1



Gence if the tissue is infected; the pG is lower8more acidic9 and according to the GG euationLthere will be less of the non-ionied form of thedrug to cross into the ner$e 8rendering the /A

less e(ecti$e9

Once some of the drug does crossL the pG in thener$e will be normal and therefore the /A re-euilibrates to both the ionied and nonionied

formsL but there are fewer cations which maycause incomplete anesthesia.

1



MODE AND SITE OF ACTION OF

LOCAL ANESTHETICS

/ocal anesthetic agent interferes with e5citationprocess in a ner$e membrane in one of thefollowing ways:

Altering the basic resting potential of ner$emembrane

Altering the threshold potential

0ecreasing the rate of depolariation

)rolonging the rate of repolariation

38



MECHANISM OF ACTION OF LOCAL

ANESTHETICS

1he following seuence is proposed mechanism ofaction of /A:

0isplacement of calcium ions from the sodiumchannel receptor site

inding of local anesthetic molecule to this

receptor site

locade of sodium channel

39



0ecrease in sodium conductance

0epression of rate of electrical depolariation

'ailure to achie$e the threshold potential le$el

/ac of de$elopment of propagated actionpotential

Con()ction loc+a(e40



Na +Na +



THECARTRIDGE



Components of the



Components of the

Cartridge 1he .! ml dental cartridge consists of four parts:

9 Cylindrical glass tube

?9 4topper 8)lunger; ung9

B9 Aluminum Cap

&9 0iaphragm

Carpule 3 registered trade name for the dentalcartridge introduced by Cooe-aite laboratories

in +?#



ubble In 1he Cartridge: -? mm bubble can befound in the cartridge which is nitrogen gas thatis inserted into the cartridge when it is sealed toeep o5ygen outL a$oids o5ygen o5idiing the

$asopressor

E5truded 4topper: liuid was froen at somepoint leading to e5trusion sterile en$ironment ofthe solution can no longer be guaranteedL itonly taes one day for alcohol to di(use through

the diaphragmL alcohol is neurolytic and can









S#$in'eCo*"onent

.9 Needle adapter

?.9 )iston withharpoon

B.9 4yringe barrel

&.9 'inger grip

,.9 1humb ring

2

A*e$ican Dental Aociation -ADA c$ite$ia fo$



acce"tance of LA #$in'e5

-0urable and re-sterilable or pacaged in a sterile

container 8if disposable9.

?-Accept a wide $ariety of cartridges and needles of

di(erent manufactures 8uni$ersal use9

B-Ine5pensi$e; light weight; and simple to use with one

hand.

&-)ro$ide e(ecti$e aspiration and the blood be easily

obser$ed in the cartridge. 1he incidence of positi$e

aspiration may be as high as #-, in some in6ection

techniues.



Needle

1he Needle 2auge: the larger the gauge thesmaller the internal diameter of the needlesual dental needle gauges are ?,;?; > B#

/ength:-/ong8appro5imately &# mm PB?-&# mmP9; for

N.

?-4hort8?#-?, mm9.B-E5tra-short8appro5imately , mm9; for )0/.

0



Components of needle

8

COMERCIALLY PREPARED LOCAL ANESTHESIA



53

COMERCIALLY PREPARED LOCAL ANESTHESIACONSISTS OF:

/ocal anesthetic agent 85ylocaine;lignocaine ?9

<asoconstrictor 8adrenaline : !#;###9

*educing agent 8sodium metabisulphite9

)reser$ati$e 8methylparaben;capryl

hydrocuprienoto5in9

'ungicide 8thymol9



REDUCING AGENT

<asoconstrictors are unstable in solution and

may o5idie especially on prolong e5posure to

sunlight this results in turning of the solution

brown and this discoloration is an indicationthat such a solution must be discarded.

1o o$ercome this problem a small uantity of

sodium metabisulphite is added - competesfor the a$ailable o5ygen.

4GE/' /I'E INC*EA4E4

54



PRESERVATIVE

Dodern local anesthetic solution are $ery

stable and often ha$e a shelf of two years

or more. 1heir sterility is maintained by the

inclusion of small amount of a preser$ati$esuch as capryl hydrocuprienoto5in.

4ome preser$ati$e such as methylparaben

ha$e been shown to allergic reaction insensitied sub6ects.

55



FUNGICIDE

In the past some solutions tended tobecome cloudy due to the proliferation ofminute fungi.

In se$eral modern solutions a small uantityof thymol is added to ser$e as fungicide andpre$ent this occurrence.

56



VEHICLE

1he anesthetic agent and the additi$es

referred to abo$e are dissol$ed in distilled

water > sodium chloride.

1his isotonic solution minimies discomfort

during in6ection.

57

C t i( C t t



Ca$t$i('e Content Local anesthetic drug is the main player !!

Calculation of mg of drug in the cartridge

○ Example: 2% lidocaine in a cartridge

"#ml$2% 2&mg'ml and (e ha)e "#ml so

2& mg'ml * "# ml , mg

this means (e ha)e ,mg of lidocaine in a cartridge

○ -o( a.out % /epi)acaine in a cartridge% &mg'ml and (e ha)e "#ml so

ans: 51mg

Dil)tion of



Dil)tion of4aocont$icto$

0ilution is commonly referred to as ratio Example1 to &&& :&&&3

Concentration of :&&& means gram &&&mg$ of solute drug$ in &&&ml solution

4o &&&mg ' &&&ml "&mg'ml of solution

5uestions: :&&1&&& dilution"""" (hat6s the concentration in mg'ml$

○ 7gain1 here mean &&&mg

○ &&&mg ' &&1&&& &"& mg'ml or & mcgm'ml

:2&&1&&& dilution"""" (hat6s the ans(er in mg'ml8 7ns(er is 9 mcgm'ml or &"&&9mg'ml you got it1 ight;

4ince you did it so good"" <f you ha)e "#ml solution of the

:&&1&&&

dilution of epi"" -o( much epi is there;8



PHARMACOKINETICS OF LOCAL

ANESTHETICSUPTAE5

hen in6ected into soft tissue most local anesthetics

produce dilation of $ascular bed.

Cocaine is the only local anesthetic that produces

$asoconstriction; initially it produces $asodilation

which is followed by prolonged $asoconstriction.

<asodilation is due to increase in the rate of

absorption of the local anesthetic into the blood; thus

decreasing the duration of pain control while

increasing the anesthetic blood le$el and potential for60

1he blood le$el is inQuenced by the following



factors:

*ate of absorption into the blood stream.

*ate of distribution of the agent from the

$ascular compartment to the tissues.

Elimination of drug through metabolic and@or

e5cretory pathways.

All local anesthetic agents readily cross the

blood-brain barrier; they also readily cross the

placenta.61

)



METABOLISM (BIOTRANSFORMATION)

E41E* /OCA/ ANE41GE1IC4:

Ester local anesthetics are hydrolyed in the plasma by the enyme pseudocholinesterase.

Chloroprocaine the most rapidly hydrolyed; is the least to5ic. 1ertracaine hydrolyed " times more slowly than Chloroprocaine ;hence it has the greatest potential

to5icity.

62



AMIDE LOCAL ANESTHETICS 1he metabolism of amide local anesthetics is more

complicated then esters. 1he primary site ofbiotransformation of amide drugs is li$er.

Entire metabolic process occurs in the li$er for

lidocaine; articaine; etidocaine; and bupi$acaine.

)rilocaine undergoes more rapid biotransformation

then the other amides.

63

EXCRETION



EXCRETION%idneys are the primary e5cretory organs for both the local

anesthetic and its metabolites

A percentage of gi$en dose of local anesthetic drug is

e5creted unchanged in the urine.

Esters appear in only $ery small concentration as the parent

compound in urine.

)rocaine appears in the urine as )AA 8+#9 and ?

unchanged.

# 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.

64

M i i



Me"i%acaine )otency: similar to lidocaine

Detabolism: /i$er Onset of action: *apid 8., to ?

mins9

Anesthetic t R : .+ hours Da5imum *ecommended 0ose

8D*09: ,",mg'=g

7.solute maximum &&mg

9"9 cartridges (ill .e maximum > used

on a patient.



Me"i%acaine

/ild )asodilating properties

Longer duration )s other agent ('o )asoconstrictor

% /epi)acaine plain pro)ides 2&8,& mins pulpal anesthesia 28 hours soft tissue anesthesia

<ndication:

?hen )asoconstrictor is N@A indicated /ost often used in pediatric ' geriatric patient

Aypes % (ithout )asoconstrictor /CB: Car.ocaine$

2% (ith )asoconstrictor Le)onodefrin $

T f



T#"e of

4aocont$icto$ Natural catecholamines Epinephrine

Norepinephrine

0opamine 4ynthetic catecholamines

<soproterenol

Le)onordefrin Non-catecholamines

7mphetamine1

Ephedrine1Dethamphetamine



REFERENCES

GAN0OO% O' /OCA/ ANE41GE4IA-

H 41AN/EH '.DA/ADE0. " 1G E01N.

/OCA/ ANE41GE4IA IN 0EN1I41*H S .A.AA*1 > G.4.*AN0.

Date post:	04-Mar-2016
Category:	Documents
Upload:	siddharth-dhanaraj
View:	215 times
Download:	0 times

DR.SID-LA YR3.pptx

Documents