Local Anesthesia - Material Indian

8/16/2019 Local Anesthesia - Material Indian

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DEPARTMENT OF ORAL MAXILLOFACIAL AND

RECONSTRUCTIVE SURGERY

LOCAL ANESTHESIA

DEFINITION NEUROPHYSIOLOGY

MODE OF ACTION

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CONTENTS

1) Introduction

2) Historic! "c#$round

%) D&'inition

() Id&! ro&rti&s o' L*A*+) P,r-co!o$. o' LA*

/ C!ssi'iction

/ P,r-co#in&tics 0 ut#& distri"ution -&t"o!is- &cr&tion

/ Indi3idu! dru$s

4) Rtin$ o' dru$s

/ S'&t.

5) Anto-ic consid&rtion

/ Structur& o' n&r3& 'i"&rs

/ Sc,6nn c&!!s nd -.&!in s,&t,

/ M.&!int&d n&r3& 'i"&rs

/ Anto-. o' -i&d n&r3&*

7) P,.sio!o$ic consid&rtions

/ E!&ctro,.sio!o$. o' n&r3& conducti3&

/ E!&ctroc,&-istr. o' n&r3& conducti3&

/ I-u!s& ro$tion

/ I-u!s& sr&d

8) Mod& nd sit& o' ction o' !oc! n&st,&tic

/ M&c,nis- o' ction

/ E''&ct o' H

/ T,&ori&s o' L*A*

19) :in&tics o' L*A*

/ Di''usion "sortion r&distri"ution &!i-intion

/ R&in;&ction11) Pot&ntition o' ction o' !oc! n&st,&tics/ 3soconstrictors

12) Sur$ic! consid&rtion

/ Pr& "!oc# &3!ution

/ As&sis

/ S#in r&rtion

1%) R&c&nt d3nc&s nd 'utur& tr&nds in in contro!

1() R&'&r&nc&s

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INTRODUCTIONLoc! n&st,&si is 6id&!. us&d nd cc&t&d -&t,od o' in contro! durin$ o&rti3& d&nt! roc&dur&* T,&

d&3&!o-&nt nd cc&tnc& o' d&nt! tr&t-&nt cn "& cr&dit&d to !oc! n&st,&si 6,ic, o''&rs 'r&&do- 'ro- in* It

!so ,&!s d&ntist to c,i&3& t,& ri-r. $o! o' t,&ir ro'&ssion i*&* in!&ss tr&t-&nt < -or& co-'ort to t,& ti&nt*

Loc! n&st,&tics ,3& !so $ot cc&tnc& durin$ o&rti3& roc&dur&s und&r $&n&r! n&st,&si*

HISTORICAL BACKGROUND

• In 18+1 Pr3&= d&scri"&d t,& ,.od&r-ic s.rin$&*

• In 17+% A!&nd&r >ood Scottis, ,.sicin in3&nt&d ,o!!o6 -&t! n&&d!&* Unti! t,is dt& it 6s di''icu!tto $i3& -&diction into tissu& or i*3*

• Cocin& is t,& 'irst !oc! n&st,&tic $&nt nd is ntur!!. occurrin$ !#!oid*• It 6s iso!t&d ". Ni&-n 'ro- t,& !&3&s o' t,& coc tr&&*• Its n&st,&tic ction 6s d&-onstrt&d ". :r! :o!!&r* In 177( ,& !i&d t,& cocin& to t,& con;ucti3 o' t,&

,u-n &.& nd roduc&d !oc! n&st,&si

• T,& 'irst &''&cti3& nd 6id&!. us&d s.nt,&tic !oc! n&st,&tic 6s rocin&• It 6s roduc&d ". Ein,orn in 189+ 'ro- "&n=oic cid nd di&t,.! -ino &t,no!*• It n&st,&tic ro&rti&s 6&r& id&nti'i&d ". ?i"&r'i&!d nd t,& $&nt 6s introduc&d into c!inic! rctic& ".

?run*

• LIDOCAINE 6s s.nt,&si=&d ". Lo'Gr&n in 18(7* T,& disco3&r. o' its n&st,&tic ro&rti&s 6s 'o!!o6&d in18(8 ". its c!inic! us& ". T* Gord,*

• T,&r&'t&r s&ri&s o' ot&nt n&st,&tic soon 'o!!o6&d 6it, 6id& s&ctru- o' c!inic! ro&rti&s*

DEFINITIONLocal anestes!a ,s "&&n d&'in&d s !oss o' s&nstion in circu-scri"&d r& o' t,& "od. cus&d ".

d&r&ssion o' &cittion in n&r3& &ndin$s or n in,i"ition o' t,& conduction roc&ss in &ri,&r! n&r3&s*

". STANLEY F* MALAMED

Local anestet!c a"ent is n. c,&-ic! c"!& o' "!oc#in$ n&r3& conduction 6,&n !i&d !oc!!. to n&r3&tissu& in conc&ntrtions t,t 6i!! not &r-n&nt!. d-$& suc, tissu&*

Va#!o$s %eto&s o' !n&$c!n" local anestes!a a#e (

i) M&c,nic! tru-

ii) Lo6 t&-&rtur&

iii) Anoi

i3) C,&-ic! irritnts

3) N&uro!.tic $&nts suc, s !co,o! nd ,&no!s

3i) C,&-ic! $&nts suc, s !oc! n&st,&tics*

IDEAL PROPERTIES OF LOCAL ANESTHESIAT,& 'o!!o6in$ r& t,& ro&rti&s d&&-&d -ost d&sir"!& 'or !oc! n&st,&tic

!) It so$l& *e non !##!tat!n" to te t!ss$es to +!c !t !s a,,l!e&-

Most o' t,& !oc! n&st,&tics r& r&!ti3&!. non irrittin$* D.c!onin& ot&nt toic! n&st,&tic is not

d-inist&r&d ". in;&ction "&cus& o' its tissu& irrittin$ ro&rti&s* On t,& ot,&r ,nd Lidocin& nd t&trcin& r&

"ot, &''&cti3& n&st,&tics 6,&n d-inist&r&d ". in;&ction or toic! !iction*

!!) It so$l& not ca$se an. ,e#%anent alte#at!on o' ne#/e st#$ct$#e-

T,& !oc! n&st,&tic so!ution s,ou!d "rin$ "out trnsitor. ionic &c,n$& or !t&rtion in t,& n&r3& -&-"rn&

< s,ou!d not cus& n. d-$& to n&r3& 'i"&rs*

!!!) Te s.ste%!c to0!c!t. so$l& *e lo+

Toicit. is d&'in&d s t,& d3&rs& r&ction o' n or$nis- to $i3&n dos& o' n $&nt* T,& &nd oint in

d&t&r-inin$ !"ortor. toicit. is 't!it.*

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T,& -ini-! -ount o' dru$ n&&d&d to #i!! +9@ o' t,& t&st ni-!s is t,& MLD +9* Toicit. -. "& &it,&r

$&n&r! or !oc!* T,& $&n&r! toicit. or s.st&-ic toicit. r&'&rs to t,& &''&ct o' dru$ on t,& &ntir& or$nis- 6,i!&

t,& !oc! toicit. r&'&rs to t,& &''&ct on c&!!u!r structur& nd is o't&n t&r-&d s c.totoicit.B*

!/) It %$st *e e''ect!/e #e"a#&less o' +ete# !t !s !n1ecte& !nto te t!ss$e o# a,,l!e& locall. to %$co$s

%e%*#anes-

i*&* t,&. s,ou!d "& ot&nt &nou$, to roduc& t,&ir ction 6it,out !oc!!. irrittin$ t,& tissu&s nd incr&sin$

t,& ris# o' s.st&-ic toicit.*

3) T,& ti-& o' ons&t o' n&st,&si s,ou!d "& s s,ort s ossi"!&*3i) T,& durtion o' ction -ust "& !on$ &nou$, t,& &r-it co-!&tion o' t,& roc&dur& .&t not so !on$ s to r&uir& n

&t&nd&d r&co3&r.*

3ii) It s,ou!d ,3& ot&nc. su''ici&nt to $i3& co-!&t& n&st,&si 6it,out t,& us& o' ,r-'u! conc&ntrt&d so!utions*

Pot&nc. o' !oc! n&st,&tic dru$ is d&'in&d s t,& -ini-! str&n$t, nd dos& o' t,& dru$ t,t roduc&s n&ur!

"!oc#d& nd ro3id&s t,& conditions d&sir&d t,t &r-it sur$&r.*

3iii) It s,ou!d "& r&!ti3&!. 'r&& 'ro- roducin$ !!&r$ic r&ctions

i) It s,ou!d "& st"!& in so!ution nd r&di!. und&r$o "io/trns'or-tion in t,& "od.*

) It s,ou!d &it,&r ". st&ri!& or "& c"!& o' "&in$ st&ri!i=&d ". ,&t 6it,out d&t&riortion*

PHARMACOLOGY OF LOCAL ANESTHETICSLoc! n&st,&tics 6,&n us&d 'or t,& -n$&-&nt o' in di''&r 'ro- -ost ot,&r dru$s co--on!. us&d in r&

3&r. i-ortnt -nn&r* irtu!!. !! ot,&r dru$s r&$rd!&ss o' t,& rout& t,rou$, 6,ic, t,&. r& d-inist&r&d -ustu!ti-t&!. &nt&r into t,& circu!tor. s.st&- in su''ici&nt!. ,i$, conc&ntrtions "&'or& t,&. cn "&$in to &&rt c!inic!

ction* Loc! n&st,&tics ,o6&3&r 6,&n us&d 'or in contro! c&s& to ro3id& c!inic! &''&ct 6,&n t,&. r&

"sor"&d 'ro- t,& sit& o' d-inistrtion into t,& circu!tion*

Class!'!cat!on o' local anestet!cs (

I. Based on the chemical structureESTERS (

!) Este#s o' *en2o!c ac!& (

/ ?utcin&

/ Cocin&

/ Et,.! -ino "&n=ot& "&n=ocin& )

/ H&.!in&

/ Pi&rocin&

/ T&trcin&*

!!) Este#s o' Pa#a a%!no *en2o!c ac!& (

/ C,!ororocin&

/ Procin&

/ Proo.cin&

AMIDES (

/ Articin&

/ ?ui3cin&

/ Di"ucin&/ Etidocin&

/ Lidocin&

/ M&i3cin&

/ Pri!ocin&

3UINOLINE (

/ C&nt"ucridin&

II. Based on biological site and mode of action :i) C!ss A $&nts ctin$ t r&c&tor sit& on &t&rn! sur'c& o' n&r3& -&-"rn& &*$* 0 t&trdotoin

sitoin*

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ii) C!ss ? $&nts ctin$ t r&c&tor sit&s on int&rn! sur'c& o' n&r3& -&-"rn& &*$* ut&rnr.

--oniu- n!o$u& o' !idocin&*

/ Scorion 3&no-

iii) C!ss C $&nt ctin$ ". r&c&tor ind&&nd&nt ,.sio/c,&-ic! -&c,nis- &*$* ?&n=ocin&

i3) C!ss D $&nts ctin$ ". co-"intion o' r&c&tor nd r&c&tor ind&&nd&nt -&c,nis-*

E*$* / Lidocin&

/ M&i3cin&

/ Procin&

III. Based on the source :i) Ntur! 0 cocin&

ii) S.nt,&tic 0 !idocin&

iii) Ot,&rs 0 &t,.! !co,o!

IV. Based on mode of application :i) Toic!

ii) In;&ct"!&

V. Based on duration of action :i) Ultra short acting (


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>it, t,& &c&tion o' cocin& !oc! n&st,&tic dru$s r& "sor"&d oor!. i' t !! 'ro- t,& GIT 'o!!o6in$

or! d-inistrtion* Addition!!. -ost !oc! n&st,&tics &s&ci!!. !idocin&) und&r$o si$ni'icnt ,&tic 'irst ss

&''&ct 'o!!o6in$ or! d-inistrtion* Fo!!o6in$ "sortion o' !idocin& 'ro- t,& GIT into t,& &n&t&ro,&tic

circu!tion 'rction o' dru$ is crri&d to t,& !i3&r 6,&r& roi-t&!. 52@ o' t,& dos& is "iotrn'or-&d into

incti3& -&t"o!it&s* T,is ,s s&rious!. ,-&r&d t,& us& o' !idocin& s n or! nti/d.srt,.t,-ic dru$*

In No3&-"&r 187( Astr &,-& 3&rtic!s introduc&d n n!o$u& o' Licocin& TOCHAINIDE

,.droc,!orid& 6,ic, is &''&cti3& or!!.*

To,!cal #o$te (Loc! n&st,&tic r& "sor"&d t di''&rin$ rt&s 't&r !iction to -ucous -&-"rn&s in t,& trc,&!

-ucos ut#& is !-ost s rid nd I d-inistrtion in ,r.n$&! -ucos ut#& is s!o6&r nd in &so,$&!

nd "!dd&r -ucos ut#& is &3&n s!o6&r t,n occurs t,rou$, t,& ,r.n*

>,&n&3&r t,&r& is no !.&r o' intct s#in r&s&nt !oc! n&st,&tics &&rt t,&ir ction 'o!!o6in$ t,& toic!

!iction* Sun"urn r&-&di&s usu!!. contin !idocin& "&n=ocin& &tc in oint-&nt 'or-u!tion* A!i&d to intct

s#in do not ro3id& n n&st,&tic ction EMLA ,s "&&n d&3&!o&d to ro3id& sur'c& n&st,&si 'or intct s#in*

In1ect!on (

T,& rt& o' ut#& o' !oc! n&st,&si 't&r in;&ction s*c* I -* i*3*) is r&!t&d to "ot, t,& 3scu!rit. o' t,&

in;&ction sit& nd t,& 3socti3it. o' t,& dru$*

i*3* Ad-inistrtion o' !oc! n&st,&tics ro3id&s t,& -ost rid &!&3tion o' "!ood !&3&!s nd is us&d in t,&

ri-r. tr&t-&nt o' 3&ntricu!r d.sr,.t,-is suc, s r&-tur& 3&ntricu!r contrctions*

$etabolism :A si$ni'icnt di''&r&nt "&t6&&n t,& t6o -;or c!ss&s o' !oc! n&st,&tics t,& &st&rs nd t,& -id&s is t,&

-&ns ". 6,ic, t,&. und&r$o -&t"o!ic "r&#do6n*

M&t"o!is- o' !oc! n&st,&tics is i-ortnt "&cus& t,& o3&r!! toicit. o' dru$ d&&nds on "!nc&s

"&t6&&n its rt& o' "sortion into t,& "!ood str&- t t,& sit& o' in;&ction nd its rt& o' r&-o3! 'ro- t,& "!ood

t,rou$, t,& roc&ss&s o' tissu& ut#& nd -&t"o!is-*

Este#s (

Est&r !oc! n&st,&tics r& ,.dro!.=&d in t,& !s- ". &n=.-& s&udoc,o!in&/&st&rs&* T,& rt& o' ,.dro!.sis

,s n i-ct on t,& ot&nti! toicit. o' !oc! n&st,&tic* C,!ororocin& t,& -ost rid!. ,.dro!.=&d (*5

µ-o!-!,r) is t,& !&st toic 6,&r& t&trcin& ,.dro!.=&d 14 ti-&s -or& s!o6!. t,n c,!ororocin& 9*%µ-o!-!,r) ,s t,& $r&t&st ot&nti! toicit.*

Procin& und&r$o ,.dro!.sis to r/-ino "&n=oic cid PA?A) nd di&t,.! -ino !co,o!* A!!&r$ic

r&ctions t,t occur in r&sons& to &st&r dru$s r& usu!!. not r&!t&d to t,& r&nt co-ound i*&* rocin& "ut rt,&r

to PA?A*

Aroi-t&!. 1 out o' &3&r. 2799 &rsons ,s n t.ic! 'or- o' s&udoc,o!in& &st&rs& 6,ic, cus&s n

in"i!it. to ,.dro!.=& &st&r !oc! n&st,&tics nd ot,&r c,&-ic!!. r&!t&d dru$ &*$* succin.!c,o!in&)* Its r&s&nc&

!&ds to ro!on$tion o' ,i$,&r "!ood !&3&!s o' t,& !oc! n&st,&tic nd n incr&s&d ot&nti! 'or toicit.*

Succin.!c,o!in& is s,ort/ctin$ -usc!& r&!nt &-!o.&d 'r&u&nt!. durin$ t,& induction ,s& o' $&n&r!

n&st,&tics* It roduc&s r&sirtor. rr&st n&) 'or &riod o' roi-t&!. 2/% -in* T,&n !s-

s&udoc,o!in&st&rs& ,.dro!.=&s succin.!c,o!in& "!ood !&3&! '!!s nd sontn&ous r&sirtion r&su-&s* P&rsons 6it,

t.ic! s&udoc,o!in& &st&rs& r& un"!& to ,.dro!.=& succin.!c,o!in& t nor-! rt& t,&r&'or& t,& durtion o'

n& is ro!on$&d*

A%!&es(

T,& -&t"o!is- o' t,& -id& !oc! n&st,&tic is -or& co-!&t& t,&- t,t o' &st&rs* T,& ri-r. sit& o'

"iotrns'or-tion o' -id& dru$s is t,& !i3&r* Pri!ocin& und&r$o&s ri-r. -&t"o!is- in t,& !i3&r 6it, so-& !so

ossi"!. occurrin$ in t,& !un$s* Pri!ocin& und&r$o&s -ost rid "iotrns'or-tion t,n t,& ot,&r -id&s*

Pti&nts 6it, !o6&r t,n usu! ,&tic "!ood '!o6 ,.ot&nsion con$&sti3& ,&rt 'i!ur&) or oor !i3&r

'unction cirr,osis) r& un"!& to "iotrns'or- -id& !oc! n&st,&tics t nor-! rt&* T,is !&ds to incr&s&d

n&st,&tic "!ood !&3&!s nd ot&nti!!. incr&s&d toicit.*

Pri!ocin& t,& r&nt co-ound cnnot roduc& -&t,&-o$!o"in&-i "ut ort,oto!uidin& ri-r.

-&t"o!it& o' ri!ocin& do&s induc& t,& 'or-tion o' -&t,&-o$!o"in 6,ic, is r&sonsi"!& 'or -&t,&-o$!o"in&-i*

Lidocin& do&s not roduc& s&dtion ,o6&3&r its t6o -&t"o!it&s 0 -ono&t,.! $!.cin&.!idid& nd

$!.cin&.!idid& 0 r& curr&nt!. t,ou$,t to "& r&sonsi"!& 'or t,is c!inic! ction*

+,cretion :

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T,& #idn&. r& t,& ri-r. &cr&tor. or$n 'or "ot, t,& !oc! n&st,&tic nd its -&t"o!it&s* A &rc&nt$& o'

$i3&n dos& o' !oc! n&st,&tic dru$ 6i!! "& &cr&t&d in t,& urin& unc,n$&d*

Est&rs &r in on!. 3&r. s-!! conc&ntrtions s t,& r&nt co-ound in t,& urin&* T,is is "&cus& t,&. r&

,.dro!.=&d !-ost co-!&t&!. in t,& !s-* A-id&s r& usu!!. r&s&nt in t,& urin& s t,& r&nt co-ound in

$r&t&r &rc&nt$& t,n r& &st&rs ri-ri!. "&cus& o' t,&ir -or& co-!& roc&ss o' "iotrns'or-tion*

Pti&nts 6it, si$ni'icnt r&n! i-ir-&nt -. "& unus"!& to &!i-int&s t,& r&nt !oc! n&st,&tic co-ound

or its -&t"o!it&s 'ro- t,& "!ood r&su!tin$ in s!i$,t!. &!&3t&d "!ood !&3&!s nd n incr&s&d ot&nti! 'or toicit.*

INDIVIDUAL LOCAL ANESTHETIC AGENTSA!t,ou$, -n. dru$ r& c!ssi'i&d s !oc! n&st,&tics nd 'ind us& 6it,in t,& ,&!t, ro'&ssions on!.

,nd'u! r& curr&nt!. us&d in d&ntistr.*

4- L!&oca!ne(Conc&ntrtion / 2@

Pot&nc. / 2 Procin&

Toicit. / 2 Procin&

M&t"o!i=&d / Li3&r

Ecr&t&d / :idn&.

@ soconstrictor Durtion2 6it,out u! / +/19 -ins

tissu& / 1/2 ,rs

2 1+9999 &i u! / 49 -ins

tissu& / %/+ ,rs

2 1199999 &i u! / 49 -ins

tissu& / %/+ ,rs

Ti-& to ons&t 2/% -ins

H!' !i'& 89 -ins

Mi-u- r&co--&nd&d dos&

M!-&d) (*( -$#$ 2 -$!")

-nu'c*)

6o &i (*( -$#$ 2 -$!")

6it, &i 4*4 -$#$ % -$!")

Mi-u- s'& dos& / 2@ 6it, 1199999&i

M!-&d / %99 -$ or 7 cru!&s

-nu'c* / +99 -$ or 1%*+ cru!&s

5- Me,!/aca!neConc&ntrtion / 2@ or %@

Pot&nc. / 2 Procin&

Toicit. / 1*+/2 Procin&

M&t"o!i=&d / Li3&r

Ecr&t&d / :idn&.

@ soconstrictor Durtion J

% 6it,out u! / 29/(9 -ins

tissu& / 2/% ,rs

2 129999 u! / 49/89 -ins

L&3onord&'rin tissu& / %/+ ,rs

2 1199999 &i u! / (+/49 -ins 1299999 &i tissu& / 2/+ ,rs

J 6&# 3sodi!tor

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Ti-& to ons&t 1*+/2 -ins

H!' !i'& 1*8 ,rs


M!-&d) (*( -$#$ 2 -$!")

-nu'c*) 4*4 -$#$ % -$!")

Mi-u- s'& dos& / %@ 6o 3soconstrictor

M!-&d / %99 -$ or +*+ cru!&s

-nu'c* / (99 -$ or 7 cru!&s

Mi-u- s'& dos& / 2@ 6it, constrictor

M!-&d / %99 -$ or 7 cru!&s

-nu'c* / (99 -$ or 11 cru!&s

6- P#!loca!neConc&ntrtion / (@

Pot&nc. / 2 Procin&

Toicit. / 1 Procin&

M&t"o!i=&d / Li3&r nd Lun$s

ort,oto!uidin& roduc&d

Ecr&t&d / :idn&.

@ soconstrictor Durtion

( 6it,out u! / 19 -ins in'i!tr*

49 -ins "!oc#

tissu& / 1*+/( ,rs

( 1299999 &i u! / 49/89 -ins tissu& / %/7 ,rs

Ti-& to ons&t 2/( -ins

H!' !i'& 1*4 ,rs


!! 'or-s 4 -$#$ 2*5 -$!")

M s'& dos&

!! 'or-s (99 -$ or +*+ cru!&s

7- B$,!/aca!neConc&ntrtion / 9*+@

Pot&nc. / 7 Procin& ( Lidocin&)

Toicit. / 7 Procin& ( Lidocin&)

M&t"o!i=&d / Li3&r

Ecr&t&d / :idn&.


9*+ 1299999 &i u! / 89/179 -ins

tissu& / (/8 ,rs

u to 12 ,rs r&ort&d

Ti-& to ons&t 4/19 -ins

H!' !i'& 2*5 ,rs

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Mi-u- r&co--&nd&d dos& 1*% -$#$ 9*4 -$!")

Mi-u- s'& dos& 89 -$ or 19 cru!&s

8- Et!&oca!ne

Conc&ntrtion / 1*+@Pot&nc. / 7 Procin& ( Lidocin&)

Toicit. / (/7 Procin& 2/( Lidocin&)

M&t"o!i=&d / Li3&r

Ecr&t&d / :idn&.


1*+ 1299999 &i u! / 89/179 -ins

tissu& / (/8 ,rs

Ti-& to ons&t 1*+/% -ins

H!' !i'& 2*4 ,rs

Mi-u- r&co--&nd&d dos& 7 -$#$ %*4 -$!")

Mi-u- s'& dos& (99 -$ or 1+ cru!&s

9- P#oca!neConc&ntrtion / 2/(@

Pot&nc. / 1

Toicit. / 1

M&t"o!i=&d / ,.dro!.=&d in !s- ". s&udoc,o!in&st&rs& to PA?A

Ecr&t&d / :idn&.

No !on$&r 3i!"!& in d&nt! cru!&s

Ti-& to ons&t 4/19 -ins

H!' !i'& 9*1 ,r Durtion u! / %9/49 -ins

6it, 3c) tissu& / 2/% ,rs

Mi-u- r&co--&nd&d dos& 4*4 -$#$ % -$!")

Mi-u- s'& dos& (99 -$

Stron$ 3sodi!tion / 3&r. s,ort durtion o' u!! n&st,&si

Hi$, incid&nc& o' !!&r$ic r&ctions

Dru$ o' c,oic& 'or T o' ind3&rtnt intr/rt&ri! in;&ction r&!i&3&s in nd ss-)

RATING OF DRUGSIn t,& s&rc, 'or -or& ot&nt nd !&ss toic $&nts si-u!tn&ous!. t,&r& ,s d&3&!o&d nu-"&r o' -&t,ods

'or t&stin$ t,&s& dru$s to &3!ut& t,&ir us&'u!n&ss nd s'&t. in c!inic! rctic&* T6o dru$s r& us&d s stndrd 'or

co-rison*

/ Procin&

/ Cocin&

• Hirs,'&!d&r nd ?i&t&r ori$in!!. r&c&i3&d -n. t&c,niu&s 'or co-rin$ cti3it. nd toicit.* Most -&t,od us&d!"ortor. ni-!s 'or initi! t&stin$ nd scr&&nin$* T,&s& inc!ud& t,& s#in o' 'ro$ corn& o' r""it nd

-usc!&/n&r3& r&rtions*

• T,& intr/d&r-! 6,&! t&c,niu& in ,u-ns ro3id&s in'or-tion "ot, on ot&nc. nd on c.totoicit. *

• A s&nsiti3& t&c,niu& to d&t&r-in& "ot, 'unction! c,n$& nd or$nic c&!!u!r c,n$& 6s t,& tissu& cu!tur&t&c,niu& d&3&!o&d ". Corss&n nd A!!&n* Ecis&d stris o' ,u-n trc,&! nd "ronc,i! -ucos 6&r&cu!ti3t&d in "!nc&d ,.sio!o$ic so!ution* T,& &!nts s,o6&d

8


10/31

continu&d ci!ir. cti3it. nd rotr. -otion nd incr&s&d or d&cr&s&d rotr. -otion is &3id&nc& o' dru$ in'!u&nc&*

A co-rti3& stud. s,o6&d t,t rocin& nd !idocin& ''&ct&d t,& tissu& t conc&ntrtion o' 9*1@ nd

'i!&d to roduc& &r-n&nt in;ur. &3&n t conc&ntrtions uto 29@* T&trcin& nd di"ucin& s,ou!d consid&r"!.

,i$,&r toicit.* Cocin& occui&d n int&r-&dit& osition*

SAFETY OF LOCAL ANESTHESIAT,& s'&t. o' !oc! n&st,&tic dru$ is d&&nd&nt on t,& r&!tion to ot&nc. to toicit.*

S'&t. α ot&nc.

I' ot&nc. is ,i$, toicit. is !o6 nd t,& -r$in o' s'&t. 6i!! "& !r$&*

• T,& rtio o' ot&nc. to toicit. is c!!&d t,& n&st,&tic ind&

SURGICAL CONSIDERATIONS

P#e:*loc; e/al$at!on(A!! ti&nts 6,o r& cndidt&s 'or r&$ion! n&st,&si s,ou!d "& co-!&t&!. &3!ut&d*

A co-!&t& ,istor. nd ,.sic! &-intion s,ou!d "& don&* It is 3&r. i-ortnt to #no6 t,& t.&s o'

-&diction t,& ti&nt -. "& t#in$ 'or 3rious -&dic! conditions* It is &u!!. i-ortnt to d&t&r-in& i' t,& ti&ntis on n. t.& o' ntico$u!nt*

Fac!l!t!es(A n&r3& "!oc# s,ou!d "& consid&r&d to "& sur$ic! roc&dur&* T,& &n3iron-&nt us&d 6,i!& &r'or-in$ t,&

t&c,niu& -ust "& $i3&n s&rious consid&rtion* T,& o"tin -i-u- succ&ss t,& o&rtin$ roo- s,ou!d ,3&

'o!!o6in$ '&tur&s

/ Pr&'&r 3&nti!tion

/ Ad&ut& !i$,tin$

/ T&-&rtur& contro!

/ Pro3isions 'or s&sisEui-&nt n&c&ssr. 'or tr&t-&nt o' co-!ictions nd dru$ r&ctions -ust "& ro3id&d* T,is inc!ud&s n

o.$&n su!. nd -&ns 'or d-inistrtion ". ositi3& r&ssur&*

Ase,s!s (As&tic r&cutions r& si-i!r to t,os& t,t tt&nd n. sur$ic! roc&dur&* T,& 'i&!d s,ou!d "& r&r&d

s,ou!d "& $i3&n s&ci! consid&rtion sinc& t,& ti&nt is not n&st,&ti=&d n. irrittin$ c,&-ic!s s,ou!d "& ?&tdin&

,3& "&&n succ&ss'u!* For outti&nts !in 59@ &t,.! or isoro.! !co,o! is -ost suit"!& sinus it is n &''&cti3&

ntis&tic !&3&s no s#in co!ortion nd doss not stin c!ot,&s* St&ri!& dr&s r& !c&d ;udicious!. 6it, r&s&ct to

t,& sit& o' t,& "!oc#*

S;!n ,#e,a#at!on (T,& c!ssic t&c,niu& o' r&rin$ t,& s#in consists o' so/6t&r scru" ndor 59@ &t,.!orisoro.!

!co,o! 'or + -inut&s* S#in contins n 3&r$& o' 299/499 "ct&ri &r sur& inc, o' sur'c& r& nd t,is t&c,niu&6i!! r&duc& t,& "ct&ri! count to !&ss t,n 199 "ct&risur& inc, 6,&n 'o!!o6&d ". t,& !iction o' 59@

&t,.!orisoro.! !co,o! t,& nu-"&r o' "ct&ri 6i!! "& r&duc&d 'urt,&r to 29/(9 "ct&ri inc,* Ho6&3&r t,& &''icc.

o' ntis&tics o3&r t,& us& o' so/6t&r !co,o! s&u&nc&s is not 6&!! &st"!is,&d*

Iodin& r&rtions r& r&co--&nd&d nd ,3& "&&n sin$u!r!. &''&cti3&* T,& disin'&ctnt ro&rt. is dir&ct!.

r&!t&d to t,& -ount o' 'r&& iodin&* Tinctur& o' iodin& 1@) ro3id&s o3&r %99- o' 'r&& iodin& o3idon&/ iodin&

"&tdin&) contins "out 29/2+-*

For -i-u- rot&ction nd t,& us& o' sin$!& !iction o' n ntis&tic c,!or,&idin& 9*+@ in 59@

&t,.!orisoro.! !co,o! or 1@ tinctur& o' iodin& is -ost &''&cti3& nd 'ro- t,& nti-icro"i! oint is r&s&nt&d s t,&

$o!d stndrd*

ANATOMIC CONSIDERATIONSTo und&rstnd t,& -od& o' ction o' !oc! n&st,&tic dru$s t,& 'und-&nt! o' n&r3&s s,ou!d "& und&rstood

t,us r&3i&6 o' t,& r&!&3nt c,rct&ristics nd ro&rti&s o' n&r3& nto-. nd ,.sio!o$. is d&scri"&d ,&r&*

19

1

Toicit.α


11/31

St#$ct$#e o' ne#/e '!*e#s(

Te ne$#onT,& n&uron or n&r3& c&!! is t,& structur! unit o' t,& n&r3ous s.st&-* T,&r& r& t6o "sic t.&s o' n&uron

• T,& s&nsor. ''&r&nt) n&uron• T,& -otor &''&r&nt) n&uron S&nsor. n&urons t,t r& c"!& o' trns-ittin$ t,& s&nstion o' in consists o' t,r&& -;or ortions* T,& d&ndritic

=on& 6,ic, is co-r&d o' n r"ori=tion o' t,& n&r3& &ndin$s is t,& -ost dist! s&$-&nts o' t,& s&nsor. n&uron*T,&s& 'r&& n&r3& &ndin$s r&sond to sti-u!tion roduc&d in t,& tissu&s in 6,ic, t,&. !i& ro3o#in$ n i-u!s& t,t is

trns-itt&d c&ntr!!. !on$ t,& on* T,& on is t,in c"!&/!i#& structur& t,t -. "& uit& !on$* At its -&si! or

c&ntr!) &nd t,&r& is n r"ori=tion si-i!r to t,t s&&n in d&ndritic =on&* Ho6&3&r in t,is co3&r t,& r"ori=tions

'ro- s.ns&s 6it, 3rious nuc!&i in t,& CNS to distri"ut& inco-in$ s&nsor.) i-u!s&s to t,&ir rorit& sit&s

6it,in t,& CNS 'or int&rr&ttion* T,& c&!! "od. or so- is t,& t,ird 'it o' t,& n&uron* In t,& s&nsor. n&uron t,&

c&!! "od. is !oct&d t distnc& 'ro- t,& on or t,& -in t,6. o' i-u!s& trns-ission in t,is n&r3&* T,& c&!!

"od. o' t,& s&nsor. n&r3& is t,&r&'or& not inc!ud&d in t,& roc&ss o' i-u!s& trns-ission its ri-r. 'unction "&in$

to ro3id& t,& 3it! -&t"o!ic suort 'or t,& &ntir& n&uron* N&r3& c&!!s t,t conduct i-u!s&s 'ro- t,& CNS &ri,&r!!. r& t&r-&d -otor n&urons nd r& structur!!.

di''&r&nt 'ro- t,& s&nsor. n&r3ous in t,t t,&ir c&!! "od. is int&ros&d "&t6&&n t,& on nd t,& d&ndrit&s* In -otor

n&urons t,& c&!! "od. not on!. is n int&$r! co-on&nt o' t,& i-u!s& trns-ission s.st&- "ut !so ro3id&s

-&t"o!ic suort 'or t,& c&!!*

M!c#osco,.R&so!ution o' t,& -&-"rn& structur& nd its ,istoc,&-istr. r&3&! "i-o!&cu!r !iid !.&r round on &c,

sid& ". rot&in s,&&t* T,& !iid -o!&cu!&s r& rrn$&d 6it, t,& ,.dro,o"ic r-s &t&ndin$ to6rd &c,

ot,&r nd t,& ,.dro,o"ic o!&s ori&nt&d to6rd &it,&r t,& &trc&!!u!r '!uid or t,& o!s-*

?&t6&&n t,& !iid -o!&cu!&s r& 6t&r 'i!!&d c,nn&!s* P&r-&"i!it. o' t,& -&-"rn& is -&dit&d ". t,&s& ion

c,nn&!s suc, c,nn&!s r& 'or-&d in t,& !iid -&-"rn& !.&rs ". 3rious s,ort/c,in &tid&s in ,&!ic! -nn&r

o' roi-t&!. 'our turns in !&n$t, t,& out&r !iorot&in -o!&cu!&s r& ti$,t!. c#&d nd i-&d& t,& -o3&-&nts o'

11


12/31

sodiu- ions -ino cids nd rot&ins "ut otssiu- nd c,!orid& ion ss r&!ti3&!. 'r&&!.* H&nc& t,& -&-"rn& is

d&si$nt&d s s&-i &r-&"!&*

Sc+ann cells an& %.el!n(

A!! n&r3& 'i"&rs r& inco-!&t&!. surround&d ". nuc!&t&d c&!!s c!!&d Sc,6nn c&!!s* As t,& -or& co-!&

n&r3ous s.st&-s ,3& &3o!3&d nd t,& n&&d rous& to rid!. con3&. s&nsor. nd -otor i-u!s&s insu!tion o' n&r3&'i"&rs "&co-& n&c&ssr.* T,is is structur!!. cco-!is,&d 'or c&rtin n&r3& 'i"&rs ". t,& s,&t, c&!!s -nu'cturin$

-.&!in 'tt. su"stnc& 6it, insu!tin$ ro&rti&s* T,is -.&!in is d&osit&d round t,& -&-"rn& o' t,& n&r3& 'i"&r

in c.!indric! o' t,& n&r3& 'i"&r in c.!indric! !.&rs or conc&ntric !-&!!&* Suc, insu!tion r&duc&s curr&nt !os&s nd

&n,nc&s t,& &''ici&nc. o' i-u!s& trns-ission*

M.el!nate& ne#/e '!*e#s (Most ---!in n&r3& 'i"&rs &c&t t,& s-!!&st r& -.&!int&d* At r&$u!r int&r3!s t,& -.&!in co!in$ is

t,in or "s&nt t,&s& oints or $s occur roi-t&!. &3&r. 9*+ 0% -- nd r& #no6n s t,& nod&s o' Rn3i&r* At

t,&s& oints t,& n&r3& 'i"&r its&!' co-&s into contct 6it, &trc&!!u!r '!uid* I-u!s&s r& t,&r& 'or& ro-u!$t&d

;u-/6is& S!ttor.) 's,ion*

It is to "& r&co$ni=&d t,t -.&!in !i-it cc&ss o' !oc! n&st,&tics to t,& n&r3& 'i"&r -&-"rn& to roduc&

conduction "!oc# in -.&!int&d 'i"&rs t,us r&uir&s ,i$,&r conc&ntrtion o' !oc! n&st,&tic* Furt,&r-or& su''ici&nt -ount o' t,& n&st,&tic -ust "& 3i!"!& nd !i&d 'or -ini-u- distnc& !on$ t,& !&n$t, o' n.

n&r3& 'i"&r usu!!. t -ini-u- sn o' t6o 0t,r&& d;c&nt nod&s) or -ini-u- distnc& o' 7/19 -- o' t,& n&r3&

-ust "& &os&d*

Anato%. o' a %!0e& ne#/e (

12


13/31

Most &ri,&r! n&r3&s r& -i&d consistin$ o' 3rious ''&r&nt nd &''&r&nt 'i"&rs ti$,t!. c#&d to$&t,&r* Indi3idu!

'i"&rs or is c.!ind&rs r& &c, cs&d ". t,in -&-"rn& or &ndon&uriu- 3ri"!& nu-"&r o' 199/1999 o' suc,

r& "ound to$&t,&r in "und!&s or 'scicu!i ". t,& &rin&uriu-* T,& &rin&uriu- o' 'scicu!us is co-r&d o' +/1+

!.&r o' 'i"ro&!stic tissu& d&&ndin$ on t,& di-&t&r o' "und!&* It is not&d t,t t,& &rin&uriu- is t,ic#&r t dist!

sit&s i*&* t t,& 6rist) t,n t t,& i!!&* Furt,&r-or& t,& inn&r -ost !.&r o' t,& &rin&uriu- t,& &ri!&-- is !in&d

6it, s-oot, -&sot,&!i! -&-"rn&* T,is &rs to "& t,& -in di''usion! "rri&r*

E-"r.o!o$ic!!. t,& &ri!&-- is continution o' t,& i / rc,noid -&-"rn& co3&rin$ t,& "rin nd

sin! cord* It is t,& &ri,&r! &ui3!&nt o' t,& contro! "!ood "rin "rri&r* A co!!&ction o' +/29 or -or& o' t,&s& "und!&s r& surround&d ". t,& &in&uriu- nd !i& in -tri o' t,& &in&ur! sc& consistin$ o' !oos& r&o!r tissu&

nutri&nt "!ood 3&ss&!s !.-,tics nd 't*

In suc, construction on& cn id&nti'. t,os& 'scicu!i t,t r& c&ntr!!. !oct&d c!!&d t,& cor& "und!&s < t,os&

6,ic, r& c!os& to t,& sur'c& or n&r3& s,&t, c!!&d t,& -nt!& "und!& o' ons*

PHYSIOLOGIC CONSIDERATIONSMn. 'und-&nt! disco3&ri&s ,3& !&d to -or& co-!&t& und&rstndin$ o' t,& ction o' !oc! n&st,&tic

$&nts* Suc, 'indin$s ,3& "&&n nto-ic ,.sio!o$ic nd "ioc,&-ic!*

T,& 'unction o' n&r3& is to crr. -&ss$&s 'ro- on& rt o' t,& "od. to not,&r* T,&s& -&ss$&s in t,& 'or-

o' &!&ctric! ction ot&nti!s r& c!!&d i-u!s&s* T,& n&r3& i-u!s& is trnsi&nt 63& o' &!&ctric! &cittion t,t

tr3&!s 'ro- oint to oint do6n to !&n$t, o' n&r3& 'i"&r*

Action ot&nti!s r& trnsi&nt -&-"rn& d&o!ri=tions t,t r&su!t 'ro- "ri&' incr&s& in t,& &r-&"i!it.

o' t,& -&-"rn& to sodiu- nd usu!!. !so 'ro- d&!.&d incr&s& in t,& &r-&"i!it. to otssiu- i-u!s&s r&

initit&d ". c,&-ic! t,&r-! -&c,nic! or &!&ctric! sti-u!i*

Note ( Onc& n i-u!s& is initit&d ". sti-u!us in n. rticu!r n&r3& 'i"&r t,& -!itud& nd s,& o' t,t i-u!s&

r&-in constnt r&$rd!&ss o' c,n$&s in t,& u!it. o' t,& sti-u!us or its str&n$t,*

T,& i-u!s& r&-ins constnt 6it,out !oosin$ str&n$t, s it ss&s !on$ t,& n&r3& "&cus& t,& &n&r$. us&d

'or its ro$tion is d&ri3&d 'ro- &n&r$. t,t is r&!&s&d ". t,& n&r3& 'i"&r !on$ its !&n$t, nd not so!&!. 'ro- t,&

initi! sti-u!us*

D& Kon$ d&scri"&d i-u!s& conduction s "&in$ !i#& t,& cti3& ro$r&ss o' sr# !on$ 'us& o' $uno6d&r*

Onc& !it t,& 'us& "urns st&di!. !on$ its !&n$t,s on& "urnin$ s&$-&nt ro3idin$ t,& &n&r$. r&uir&d to i$nit& its

n&i$,"our suc, is t,& sitution 6it, i-u!s& ro$tion !on$ n&r3&*

ELECTROPHYSIOLOGY OF NERVE CONDUCTION (

1%


14/31

T,& 'o!!o6in$ is d&scrition o' &!&ctric! &3&nts t,t occur 6it,in n&r3& durin$ t,& conductin$ o' n

i-u!s&

Ste, 4 (

A n&r3& roc&ss&s r&stin$ ot&nti!* T,is is n&$ti3& &!&ctric! ot&nti! o' 19- t,t &ists cross t,&

n&r3& -&-"rn& roduc&d ". di''&rin$ conc&ntrtions o' ion on &it,&r sid& o' t,& -&-"rn&* T,& int&rior o' t,& n&r3&

is n&$ti3& in r&!tion to t,& &t&rior*

Ste, 5 (

A sti-u!us &cit&s t,& n&r3& !&din$ to 'o!!o6in$ s&u&nc& o' &3&nts*

) An initi! ,s& o' s!o6 d&o!ri=tion t,& &!&ctric! ot&nti! 6it,in t,& n&r3& "&co-&s s!i$,t!. !&ss n&$ti3&* ") >,&n t,& '!!in$ &!&ctric! ot&nti! r&c,&s critic! !&3&! n &t&rn!!. rid ,s& o' d&o!ri=tion r&su!ts

t,is is t&r-&d s t,r&s,o!d ot&nti! or 'irin$ t,r&s,o!d*

T,& 'irin$ t,r&s,o!d is ctu!!. t,& -$nitud& o' t,& d&cr&s& in n&$ti3& trns-&-"rn& ot&nti! t,t is

r&uir&d to initit& n ction ot&nti! i-u!s&)*

c) T,is ,s& o' rid d&o!ri=tion r&su!ts in r&3&rs! o' t,& &!&ctric! ot&nti! cross t,& n&r3& -&-"rn&*

T,& int&rior o' t,& n&r3& is no6 &!&ctric!!. ositi3& in r&!tion to t,& &t&rior* An &!&ctric! ot&nti! o'

(9- &ists on t,& int&rior o' t,& n&r3& c&!!*

Ste, 6 (

Fo!!o6in$ t,&s& st&s o' d&o!ri=tion r&o!ri=tion occurs* T,& &!&ctric! ot&nti! $rdu!!. "&co-&s

-or& n&$ti3& insid& t,& n&r3& c&!! r&!ti3& to t,& outsid& unti! t,& ori$in! r&stin$ ot&nti! o' 19- is $in

c,i&3&d*T,& &ntir& roc&ss r&uir&s 1-s&c d&o!ri=tion t#&s 9*%-s&c nd d&o!ri=tion t#&s 9*5-s&c*

ELECTROCHEMISTRY OF NERVE CONDUCTION (T,& r&c&din$ s&u&nc& o' &3&nts d&&nds on t6o i-ortnt 'ctors*

i) T,& conc&ntrtion o' &!&ctro!.t&s in t,& o!s- int&rior o' t,& n&r3& c&!!) nd &trc&!!u!r '!uids*

ii) T,& &r-&"i!it. o' t,& n&r3& -&-"rn& to sodiu- nd otssiu- ions*

INTRACELLULAR AND EXTRACELLULAR IONIC CONCENTRATIONS

Ion Int#acell$la#


15/31

MEMBRANE EXCITATION (

De,ola#!2at!on ( Ecittion o' n&r3& s&$-&nt to n incr&s& in &r-&"i!it. o' t,& c&!! -&-"rn& to sodiu- ions*

T,is is cco-!is,&d ". trnsi&nt 6id&nin$ o' trns-&-"rn& ion c,nn&!s su''ici&nt to &r-it t,& un,ind&r&d

ss$& o' ,.drt&d sodiu- ions* T,& rid in'!u o' sodiu- ions to t,& int&rior o' t,& n&r3& c&!! cus&s

d&o!ri=tion o' t,& n&r3& -&-"rn& 'ro- its r&stin$ !&3&! to its 'irin$ t,r&s,o!d o' roi-t&!. +9/59-*

Eosur& o' t,& n&r3& to !oc! n&st,&tic "sis its 'irin$ t,r&s,o!d)*

>,&n 'irin$ t,r&s,o!d is r&c,&d &r-&"i!it. o' t,& -&-"rn& to sodiu- incr&s&s dr-tic!!. nd sodiu- ion

rid!. &nt&rs t,& o!s-* At t,& &nd o' d&o!ri=tion t,& !t& o' ction ot&nti!) t,& &!&ctric! ot&nti! o' t,&

n&r3& is ctu!!. r&3&rs&d n &!&ctric! ot&nti! o' (9- &ists* T,& &ntir& d&o!ri=tion r&uir&s 9*%-s&c*

D&o!ri=tion T,& ction ot&nti! is t&r-int&d 6,&n t,& n&r3& r&o!ris&s* T,is is cus&d ". &tinction or incti3tion o' incr&s&d &r-&"i!it. to sodiu-* In -n. c&!!s &r-&"i!it. to otssiu- !so incr&s&s r&su!tin$ in

t,& &''!u o' : !&din$ to -or& rid -&-"rn& r&o!ri=tion nd r&turn to its r&stin$ ot&nti!*

T,& -o3&-&nt o' sodiu- ions into t,& c&!! durin$ d&o!ri=tion nd su"s&u&nt -o3&-&nt o' otssiu- ions

out o' t,& c&!! durin$ r&o!ri=tion r& ssi3& not r&uirin$ t,& &&nditur& o' &n&r$. ri3&r t,& ions -o3&s !on$

t,&ir conc&ntrtion $rdi&nt*

Acti3& trns'&r o' sodiu- ion out o' t,& c&!! occur 3i t,& sodiu- u-* An &&nditur& o' &n&r$. is n&&d&d

to -o3& sodiu- ions out o' t,& n&r3& c&!! $inst t,&ir conc&ntrtion $rdi&nt t,is &n&r$. co-&s 'ro- t,& oidti3&

-&t"o!is- o' ATP*

T,& &ntir& roc&ss o' r&o!ri=tion r&uir&s 9*5-s&c

I--&dit&!. 't&r sti-u!us ,s initit&d n ction ot&nti! n&r3& is un"!& 'or ti-&) to r&sond to

not,&r sti-u!us r&$rd!&ss o' its str&n$t,* T,is is t&r-&d t,& "so!ut& r&'rctor. &riod* T,is is 'o!!o6&d ". r&!ti3&

r&'rctor. &riod durin$ 6,ic, n&6 i-u!s& cn "& initit&d "out on!. ". stron$&r t,&ir nor-! sti-u!us* T,&r&!ti3& r&'rctor. &riod continuous to d&cr&s& unti! t,& nor-! !&3&! o' &cit"i!it. r&turns t 6,ic, oint t,& n&r3&

is sid to "& r&o!ris&d*

T,& ntur& o' n&r3& conduction is su--ri=&d s d&o!ri=tion 0 r&o!ri=tion roc&ss*

$embrane channels :Discr&t& u&ous or&s t,rou$, t,& &cit"!& n&r3& -&-"rn& c!!&d sodiu- or ion) c,nn&!s r& -o!&cu!r

structur&s t,t -&dit& its sodiu- &r-&"i!it.* T,& c,nn&! is !io$!.corot&in 'ir-!. situt&d in t,& -&-"rn&* It

consists o' n u&ous or& snnin$ t,& -&-"rn& t,t is nrro6 &nou$, t !&st t on& oint to discri-int&

"&t6&&n sodiu- nd ot,&r ions* N oss&s t,rou$, 12 ti-&s -or& &si!. t,n : ) t,& c,nn&! !so inc!ud&s ortion

t,t c,n$&s con'i$urtion in r&sons& to c,n$& in -&-"rn& ot&nti! t,&r&". $tin$ t,& ss$& o' t,& ions

t,rou$, t,& or&* Sodiu- c,nn&!s ,3& n int&rn! di-&t&r o' roi-t&!. 9*% 9*+ n-*

A sodiu- ion is t,inn&r t,n &it,&r otssiu- or c,!orid& ion nd s,ou!d t,&r&'or& di''us& '&&!. do6n its

conc&ntrtion $rdi&nt t,ou$,t -&-"rn& c,nn&!s into t,& n&r3& c&!!s* T,is do&s not occur ,o6&3&r "&cus& !!

1+


16/31

t,&s& ions ttrct 6t&r -o!&cu!&s nd t,us "&co-& ,.drt&d* H.drt&d sodiu- ions ,3& rdius o' %*( A 9 6,ic, is

$r&t&r t,n 2*2A9 rdius o' otssiu- nd c,!orid& ions* Sodiu- ions r& t,&r&'or& too c,r$& to ss t,rou$, t,&

nrro6 c,nn&!s 6,&n n&r3& is t r&st*

R&c&nt &3id&nc& indict&s t,t c,nn&! s&ci'icit. &ists in t,t t,& sodiu- c,nn&!s di''&r 'ro- otssiu-

c,nn&!s*

T,& $t&s on t,& sodiu- c,nn&!s r& !oct&d n&r t,& &t&rn! sur'c& o' t,& n&r3& -&-"rn& 6,&r&s t,os&

n t,& otssiu- c,nn&! r& !oct&d n&r t,& int&rn! sur'c& o' t,& n&r3& -&-"rn&*

IMPULSE PROPAGATION (Fo!!o6in$ t,& initition o' n ction ot&nti! ". sti-u!us t,& i-u!s& -ust -o3& !on$ t,& sur'c& o' t,&on* En&r$. 'or i-u!s& ro$tion is d&ri3&d 'ro- t,& n&r3& -&-"rn& is t,& 'o!!o6in$ -nn&r

T,& sti-u!us disruts t,& r&stin$ &ui!i"riu- o' t,& n&r3& -&-"rn& t,& trns -&-"rn& ot&nti! is r&curr&d

-o-&ntri!. 0 t,& int&rior o' t,& c&!! c,n$in$ 'ro- n&$ti3& to ositi3& nd t,& &t&rior c,n$in$ 'ro- ositi3& to

n&$ti3&* T,is no6 &!&ctric! &ui!i"riu- in t,is s&$-&nt o' n&r3& roduc&s !oc! curr&nts t,t "&$in '!ourin$ "&t6&&n

t,& d&o!ri=&d s&$-&nt nd t,& d;ustin$ r&stin$ r&* T,&s& !oc! curr&nts '!o6 'ro- ositi3& to n&$ti3& &t&ndin$

'or s&3&r! -- !on$ t,& n&r3& -&-"rn&*

As r&su!t o' t,is curr&nt '!o6 t,& int&rior o' t,& d;c&nt r& "&co-&s !&ss n&$ti3& nd its &t&rior !&ss

ositi3&* Trns -&-"rn& ot&nti! d&cr&s&s roc,in$ 'irin$ t,r&s,o!d 'or d&o!ri=tion* >,&n t,& trns

-&-"rn& ot&nti! is d&cr&s&d ". 1*+- 'ro- r&stin$ ot&nti! 'irin$ t,r&s,o!d is r&c,&d nd co-!&t&

d&o!ri=tion occurs* T,& n&6!. d&o!ri=&d s&$-&nt s&ts u !oc! curr&nt in d;c&nt r&stin$ -&-"rn& nd t,&&ntir& roc&ss strts n&6*

Conditions in t,& s&$-&nt t,t ,s 'irst d&o!ri=&d r&turn to nor-! 'o!!o6in$ t,& "so!ut& nd r&!tion

r&'rctor. &riods* ?&cus& o' t,is t,& 63& o' d&o!ri=tion cn sr&d in on!. on& dir&ction* ?c#6rd r&tro$rd&)

-o3&-&nt is r&s&nt&d ". t,& un&cit"!& r&'rctor. s&$-&nt*

IMPULSE SPREAD (T,& ro$t&d i-u!s& tr3&!s !on$ t,& n&r3& -&-"rn& to6rd t,& CNS* T,& sr&d t,& i-u!s& di''&rs

d&&ndin$ on 6,&t,&r or not n&r3& is -.&!int&d*

Unm-elinated ner'es :

An un-.&!int&d n&r3& 'i"&r is "sic!!. !on$ c.!ind&r 6it, ,i$,/&!&ctric! r&sistnc& c&!! -&-"rn&surroundin$ !o6 r&sistnc& conductin$ cor& o' o!s- !! o' 6,ic, is "t,&d in !o6 r&sistnc& &trc&!!u!r '!uid*

14


17/31

T,& ,i$, r&sistnc& c&!! -&-"rn& nd !o6 r&sistnc& intrc&!!u!r nd &trc&!!u!r -&di roduc& rid

d&cr&s& in t,& d&nsit. o' curr&nt 6it,in s,ort distnc& o' t,& d&o!ri=&d s&$-&nt* In r&s i--&dit&!. d;c&nt to

t,is d&o!ri=&d s&$-&nt !oc! curr&nt '!o6 -. "& d&ut& to initit& d&o!ri=tion in t,& r&stin$ -&-"rn&*

Furt,&r -on$ it 6i!! ro3& to "& ind&ut& to c,i&3& 'irin$ t,r&s,o!d*

T,& sr&d o' n i-u!s& is cn un-.&!int&d n&r3& 'i!&rs is t,&r&'or& c,rct&ri=&d s r&!ti3&!. s!o6

'or6rd 0 cr&&in$ roc&ss*

$-elinated ner'es :

I-u!s& conduction in -.&!int&d n&r3& occurs ". -&ns o' curr&nt !& 'ro- nod& to nod& 0 roc&sst&r-&d s s!uttor. conduction* s!t r& is t,& !tin 3&r" to !&* T,is 'ro- o' i-u!s& conduction roc&ss to "&

-uc, 'st&r nd -or& &n&r$. &''ici&nt t,n t,t 6,ic, is &-!o.&d in un-.&!int&d n&r3&s*

MODE AND SITE OF ACTION OF LOCAL ANESTHETIC (It is ossi"!& 'or t,& !oc! n&st,&tic $&nts to int&r'&r& 6it, t,& &cittion roc&ss in n&r3& -&-"rn& in on&

or -or& o' t,& 'o!!o6in$ 6.s

i) A!t&rin$ t,& "sic r&stin$ ot&nti! 'or t,& n&r3&

ii) A!t&rin$ t,& t,r&s,o!d ot&nti!

iii) D&cr&sin$ t,& rt& o' d&o!ri=tion

i3) Pro!on$in$ t,& rt& o' r&o!ri=tion

It ,s "&&n &st"!is,&d t,t t,& ri-r. &''&cts o' !oc! n&st,&tic occur durin$ t,& d&o!ri=tion ,s& o' t,&

ction ot&nti!* T,&s& &''&cts inc!ud& d&cr&s& in t,& rt& o' d&o!ri=tion rticu!r!. in t,& ,s& o' s!o6d&o!ri=tion* ?&cus& o' t,is c&!!u!r d&o!ri=tion is not su''ici&nt to r&duc& t,& -&-"rn& ot&nti! to 'irin$

!&3&! nd ro$t&d ction ot&nti! do&s not d&3&!o*

S!te (T,& n&r3& -&-"rn& is t,& sit& t 6,ic, !oc! n&st,&tic $&nt &&rt t,&ir ,r-co!o$ic ctions*

Mecan!s% o' act!on (T,& !oc! n&st,&tic is 6&# "s& 6,ic, -ust "& co-"in&d 6it, stron$ cid in ord&r to -#&s t,& cid s!t

t,t is so!u"!& 'or us& in so!ution*

RNHOH HC!

RNHCL H2O>&# stron$ cid 6t&r

?s& cid s!t

To ct s !oc! n&st,&tic it -ust dissocit& into 'r&& "s& 'or 6,ic, "sic &n3iron-&nt 'ound in nor-!

tissu& is n&c&ssr.*

RNHCI RNH CI/

T,is ositi3&!. c,r$&d RNH) -o!&cu!&s is c!!&d c&rtin nd is ,.dro,i!ic* It 'urt,&r dissocit&d outsid&

t,& n&r3& s,&t, r&su!tin$ in n unioni=&d !io,i!!ic -o!&cu!& c!!&d t,& "s&RNH RN H

15


18/31

T,& r&!ti3& roortion o' &c, ionic 'orin t,& so!ution cri&s 6it, t,& H o' t,& surroundin$ tissu&s* In

cidic &n3iron-&nt !o6 H) t,& &ui!i"riu- s,i'ts to t,& !&'t nd -ost o' t,& n&st,&tic so!ution &ists in ctionic

'or-

RNH RN H

As ,.dro$&n ion conc&ntrtion d&cr&s&s ,i$,&r H) t,& &ui!i"riu- s,i't to6rd t,& 'r&& "s& 'or-

RNH

RN H

T,& r&!ti3& roortion o' t,& ionic 'or-s !so d&&nds on t,& : or dissocition constnt o' t,& s&ci'ic

!oc! n&st,&tic* T,& : is -&sur& o' -o!&cu!&s ''init. 'or ,.dro$&n ions H )* >,&n t,& H o' so!ution ,s

t,& s-& 3!u& s t,& : o' t,& !oc! n&st,&tic dru$ &ct!. ,!' t,& dru$ 6i!! &ist in t,& RNH 'or- nd ,!' in

RN 'or-*

T,& &rc&nt$& o' dru$ &istin$ in &it,&r 'or- cn "& d&t&r-in&d 'or t,& H&nd&rson 0 Hss&!"!c, &ution

T,is non ioni=& !io,i!!ic !oc! n&st,&tic -o!&cu!&s RN) di''us&s r&di!. t,rou$, t,& !iid co-os&d n&r3&

s,&t,* A't&r ,is -o!&cu!&s ss$& into t,& int&rstiti! '!uid "&t6&&n t,& n&r3& s,&t, nd t,& n&r3& c&!! -&-"rn&*H&r& it und&r$o&s not,&r r&ction 6i!! t,& 'or ,.dro$&n 'ound ,&r&* T,is 'r&& ,.dro$&n ion is !i"&rt&d 'ro- t,&

"u''&r s.st&- r&ction ccordin$ in t,& r&* T,& r&ction r&su!ts in t,& 'or-tion o' n ioni=&d ,.dro,i!ic 'or- o'

!oc! n&st,&tic -o!&cu!&*

RN H RNH

T,is -o!&cu!& in n&r3& c!! -&-"rn& dis!c&s c!ciu- ions 'or t,& sodiu- c,nn&! r&c&tor sit&*

↓

?indin$ o' t,& !oc! n&st,&tic -o!&cu!&s to t,is r&c&tor sit&

↓

?!oc#d& o' sodiu- c,nn&!

↓

D&cr&s& in sodiu- conduction

↓

D&r&ssion o' t,& rt& o' &!&ctric! d&o!ri=tion

↓

Fi!ur& to c,i&3& t,& t,r&s,o!d ot&nti! !&3&!

↓

Lc# o' d&3&!o-&nt o' ro$t&d ction ot&nti!s

↓

Con&$ct!on *loc;a&e

THEORIES OF MECHANISM OF ACTION OF L-A-Mn. t,&ori&s ,3& "&&n roos&d o3&r t,& .&rs to &!in t,& -&c,nis- o' ction o' !oc! n&st,&tics*

!) Acet.l co#!ne teo#. (Accordin$ to t,is t,&or. !i"&rtion o' c&t.! c,orin& t s.ntic 'unction !t&rs t,& &r-&"i!it. o' !s-

-&-"rn& nd &r-its d&o!ri=tion 6,ic, is r&sonsi"!& 'or continuous u!s&/trns-ission* T,& !oc! n&st,&tic$&nts r&3&nts t,& d&o!ri=tion nd u!s& trns-ission ". t,&ir &''&ct on c&t.! c,orin&*

17

Lo$ ?s&

AcidQ H 0 :


19/31

T,is t,&or. is not cc&t&d "&cus& c&t.! c,orin& is t,& n&urotrns-itt&r t t,& s.ntic 'unction t,&r& is no &3id&nc&

t,t c&t.! c,orin& is in3o!3&d in n&ur! trns-ission !on$ t,& "od. o' t,& n&uron*

!!) Calc!$% &!s,lace%ent teo#. (T,is t,&or. 6s onc& uit& ou!r nd -intin&d t,t !oc! n&st,&tic n&r3& "!oc# 6s roduc&d ". t,&

dis!c&-&nt o' c!ciu- 'ro- so-& -&-"rn& sit&s t,t contro!!&d &r-&"i!it. to sodiu-*

E3id&nc& t,t 3r.in$ t,& conc&ntrtion o' c!ciu- ions "t,in$ n&r3& do&s not &''&ct !oc! n&st,&tic

ot&nc. ,s di-inis,&d t,& cr&di"i!it. o' t,is t,&or.*

!!!) S$#'ace ca#"e


20/31

T,is t,&or. s&r3& n ossi"!& &!ntion 'or t,& !oc! n&st,&tic cti3it. o' dru$ suc, s "&n=ocin& 6,ic, do&s

not &ist in ctionic 'or- .&t sti!! &,i"its ot&nt toic! n&st,&tic cti3it.* It ,s "&&n d&-onstrt&d t,t n&r3&

-&-"rn& do in'&ct &nd nd "&co-& -or& '!uidB 6,&n &os&d to !oc! n&st,&tics* Ho6&3&r t,&r& is no dir&ct

&3id&nc& t,t n&r3& conduction is &ntir&!. "!oc#&d ". -&-"rn& &nsion &r s&*

/) S,ec!'!c #ece,to# teo#. (It is t,& -ost 'or6rd t,&or. tod. nd roos&s t,t !oc! n&st,&tics ct ". "indin$ to s&ci'ic r&c&tors on

t,& sodiu- c,nn&!* T,& ction o' t,& dru$ is dir&ct nd not -&dict&d ". so-& c,r$& in t,& $&n&r! ro&rti&s o' t,&c&!! -&-"rn&* ?ot, "ioc,&-ic! nd &!&ctro,.sio!o$ic! studi&s ,3& indict&d t,t s&ci'ic r&c&tor sit& 'or !oc!

n&st,&tic $&nts &ist in t,&

29


21/31

sodiu- c,nn&! &it,&r on its &t&rn! sur'c& or on t,& int&rn! o!s-ic sur'c&* Onc& t,& !oc! n&st,&tic ,s

$in&d cc&ss to t,& r&c&tors &r-&"i!it. to sodiu- ions is d&cr&s&d or &!i-int&d nd n&r3& conduction is

int&rrut&d*

KINETICS OF LOCAL ANESTHETICS>,&n !oc! n&st,&tics dru$ is in;&ct&d nd d&osit&d "out t,& n&r3& "und!& dru$ -o3&-&nt into t,& n&r3&

"und!& nd into indi3idu! n&r3& c&!!s 'o!!o6s r&$u!r s&ri&s o' st&s to c,i&3& stt& o' n&r3& "!oc#*

Fours s&ct r& to "& consid&r&d 6it, r&s&ct to ons&t nd -int&nnc& o' t,& stt& o' "!oc#* T,& r&uir& o'

-o3&-&nt is s 'o!!o6sii) Di''usion to t,& n&r3& nd into t,& n&r3& "und!&s* T,is d&&nds on t,& u&ous so!u"i!it.*

iii) Proc&ss o' &n&trtion into t,& n&r3& c&!!* T,is d&&nds on non ioni=&d "s&) 'or-*

i3) R&tri"ution o' t,& $&nt in n&r3& 'i"&r c&!!* T,is d&&nds on u&ous so!u"i!it.

3) T,& 'ition to t,& n&r3& c&!! co-on&nts* T,is d&&nds on t,& ''init. o' ction 'or- to c,nn&!

r&c&tors*

As t,& n&st,&tic stt& is "&in$ &st"!is,&d t,& roc&ss o' r&-o3! o' t,& dru$ 'ro- t,& sit& o' in;&ction into t,&

3scu!r sc& "&$in* T,& roc&ss&s "&co-& -or& ro-in&nt 6it, t,&ir nd 'our s&cts o' r&co3&r. 'ro- "!oc#

nd disosition o' dru$ -. "& consid&r&d

i) A"sortion Etrc&!!u!r dru$ &nt&rs t,& 3scu!r sc&s nd continuous durin$ n&st,&tic "!oc#*

ii) R&!&s& roc&ss T,& n&r3& 'i"&r r&!&s&s t,& 'i&d dru$ s t,& $rdi&nt o' conc&ntrtion r&3&rs&s 6it,

ti-&*

iii) R&distri"ution to ot,&r or$ns nd tissu&s occurs 't&r "sortioni3) D&struction nd &!i-intion*

DIFFUSION OF LOCAL ANESTHETICS (Fo!!o6in$ t,& d-inistrtion o' !oc! n&st,&tic into t,& so't tissu&s n&r n&r3& !oc! n&st,&tic so!ution

s,ou!d "& d&osit&d s n&r to t,& n&r3& s ossi"!& 6it,out &n&trtin$ or s&rin$ t,& n&r3& s,&t,* An in;&ction into

t,& &rin&ur! sc& 6i!! co-r&ss t,& n&r3& "und!&s nd !so cus& isc,&-i) t,& -o!&cu!&s o' t,& !oc! n&st,&tic

trns3&rs& t,& distnc& 'ro- on& sit& to not,&r ccordin$ to t,&ir conc&ntrtion $rdi&nt*

Durin$ t,& induction ,s& o' n&st,&si t,& !oc! n&st,&tic -o3&s 'ro- its &trn&ur! sit& o' d&osition to6rd t,&

n&r3& s 6&!! is in !! t,& ot,&r dir&ction)* T,is roc&ss is t&r-&d s di''usion* It is t,& un,ind&r&d -i$rtion o'

-o!&cu!&s or ions t,rou$, '!uid -&diu- und&r t,& in'!u&nc& o' t,& conc&ntrtion $rdi&nt &n&trtion o' n

nto-ic! "rri&r to di''usion occurs 6,&n dru$ ss&s t,rou$, tissu& t,t t&nds to r&strict t,& -o!&cu!r

-o3&-&nt* T,& &rin&uriu- is t,& $r&t&st "rri&r to &n&trtion o' !oc! n&st,&tics*

Di''usion n &n&trtion r& r&!ti3&!. s!o6 roc&ss nd s&&d o' o3&rt o' n&st,&tic ction is &ss&nti!!.

roortion! to t,& !o$ o' conc&ntrtion o' t,& dru$ i*&* t,& rt& o' di''usion is $o3&rn&d ". t,& conc&ntrtion $rdi&nt

t,& $r&t&r t,& initi! conc&ntrtion o' t,& !oc! n&st,&tic t,& 'st&r 6i!! "& t,& di''usion*

Mnt!& "und!&s on& t,& 'irst on&s r&c,&d ". !oc! n&st,&tic nd r& &os&d to ,i$,&r conc&ntrtion o' it*

T,&. r& usu!!. "!oc#&d co-!&t&!. s,ort!. 't&r t,& in;&ction o' !oc! n&st,&tic* Cor& "und!&s r& contct&d ". t,&

21


22/31

dru$ on!. 't&r -uc, d&!. nd ". !o6&r n&st,&tic conc&ntrtion "&cus& o' t,& $r&t&r distnc& t,t t,& so!ution

-ust trns3&rs& nd t,& $r&t&r nu-"&r o' "rri&r it -ust cross*

As t,& !oc! n&st,&tic di''us&s into t,& n&r3& it "&co-&s incr&sin$!. di!ut&d ". tissu& '!uids nd is "sor"&d

". ci!!ri&s nd !.-,tics &st&r n&st,&tics und&r$o !-ost i--&dit& &n=.-tic ,.dro!.sis* T,us t,& cor& 'i"&rs

r& &os&d to d&cr&s&d conc&ntrtion o' !oc! n&st,&tic 't t,t -. &!in t,& c!inic! sitution o' ind&ut&

Pu!! n&st,&si d&3&!oin$ in t,& r&s&nc& o' su";&cti3& s.-to-s o' d&ut& o't tissu& n&st,&si*

Fi"&rs n&r t,& sur'c& o' t,& n&r3& -nt!& 'i"&rs) t&nd to inn&r3t& -or& roi-! r&$ions &*$* -o!r r&

6it, n in'&rior !3&o!r n&r3& "!oc#) 6,&r&s 'i"&rs in t,& cr& "und!&s inn&r3t& t,& -or& dist! oints o' n&r3&

distri"ution &*$* incisors)*Liid so!u"i!it. o' !oc! n&st,&tic &rs to "& r&!t&d to its intrinsic ot&nc.* Loc! n&st,&tics 6it,

$r&t&r !iid so!u"i!it. roduc& -or& &''&cti3& conduction "!oc#d& t !o6&r conc&ntrtions t,n do t,& !&ss !iid

so!u"!& so!utions*

T,& d&$r&& o' rot&in "indin$ o' t,& n&st,&tic -o!&cu!& is r&sonsi"!& 'or t,& durtion o' !oc! n&st,&tic

cti3it.* socti3it. ''&ct "ot, t,& n&st,&tic ot&nc. nd t,& durtion o' n&st,&si ro3id&d ". dru$*

A*so#,t!on (A't&r in;&ction o' !oc! n&st,&tic $&nt nd &osur& o' $rin n&r3& to its &''&ct t,& $&nt is di!ut&d in t,&

&trc&!!u!r '!uid nd t#&n u ". ci!!ri&s* U!ti-t&!. !! o' t,& $&nts &nt&rs t,& "!ood st&-*

T,& "!ood su!. to tissu& is cruci! 'ctor in d&t&r-inin$ rt& o' "sortion* Dir&ct i*3* in;&ction ro3id&s

t,& -ost rid "sortion rt& nd roduc&s ,i$, !s- !&3&!s* Toic! !iction to -n. -ucous -&-"rn&s

r&su!ts in t,& n&t ,i$,&st !s- !&3&!s* ind&&d !iction to t,& ,r.n nd trc,&o/"ronc,i! tr&& -. roduc& "!ood !&3&!s co-r"!& to s!o6 i*3* in;&ction*

I*-* in'&ction o' !oc! n&st,&tics ro3id& t,& n&t ,i$,&st !&3&!s* T,& !o6&st !&3&!s occurs 't&r su"cutn&ous

nd intrcutn&ous in'&ctions* 3soconstrictor $&nts 'urt,&r !i-it t,& "sortion o' $&nts 'ro- t,&r& sit&s*

No "sortion occurs t,rou$, un"ro#&n s#in "ut i' t,& s#in is "rd&d si$ni'icnt !s- !&3&!s r& ttin&d*

In "urn sit& t,& "sortion d&&nds on t,& d&$r&& o' t,& "urn*

D!s,os!t!on (Litt!& or no d&struction o' !oc! n&st,&tics occurs in situ t t,& tissu& sit&s o' in;&ction* T,is cn "& &!in&d

". n &-!&* C,!orrocin& ro3id&s !oc! "!oc# 'or -or& t,n 1,ours 6,i!& t,& $&nt und&r$o co-!&t&

,.dro!.sis in !s- 6it,in + -inut&s*

Re&!st#!*$t!on (A r&distri"ution to ot,&r or$ns nd tissu&s r&-ot& 'ro- t,& sit& o' in;&ction &nsu&s* Conc&ntrtion in t,&s& is

d&&nd&nt on r&$ion! "!ood '!o6* T,os& or$ns t,t r& usu! ric, 6it, ,i$, "!ood '!o6 suc, s t,& !in$ !i3&r nd

#idn&. conc&ntrt& -or& -ount o' dru$* T,& $r&t&st &rc&nt$& o' n in;&ct&d dos& distri"ut&s to s#&!&t! -usc!&

du& to its !r$& -ss*

Dest#$ct!on (D&toi'iction is ri-ri!. d&&nd&nt on !i3&r &n=.-&s* ?r&&d&do6n o' &st&rs occurs in t,& !s-* T,&

ri-r. sit& o' -id& -&t"o!is- is t,& !in&r*

REIN>ECTION OF LOCAL ANESTHETIC

Not in'r&u&nt!. d&nt! roc&dur& 6i!! out!st t,& durtion o' c!inic!!. &''&cti3& in contro! nd r&&ntin'&ction o' !oc! n&st,&tic 6i!! "& r&uir&d*

Rec$##ence o' !%%e&!ate ,#o,o$n& anestes!a (At t,& t,is o' r&in;&ction t,& conc&ntrtion o' !oc! n&st,&tic in t,& -nt!& 'i"&rs is "&!o6 t,t in t,& -or&

c&ntr!!. !oct&d cor& 'i"&rs* T,& rti!!. r&co3&r&d -nt!& 'i"&rs sti!! contin so-& !oc! n&st,&tic !t,ou$, not

&nou$, to ro3id& co-!&t& n&st,&si*

A't&r d&osition o' n&6 ,i$, conc&ntrtion o' n&st,&tic t,& n&r3& t,& -nt!& 'i"&rs r& onc& $in &os&d

to conc&ntrtion $rdi&nt dir&ct&d in6rd to6rd t,& n&r3&* T,is co-"intion o' r&sidu! !oc! n&st,&tic nd t,&

n&6!. d&osition su!. r&su!ts in rid ons&t o' ro'ound n&st,&si 6it, s-!! 3o!u-& o' !oc! n&st,&tic dru$

"rin$ d-inist&r&d*

D!''!c$ltl. !n #e:ac!e/!n" ,#o'o$n& anestes!a (In t,is sitution &''&cti3& contro! o' in do&s not occur &3&n 't&r r&in;&ction o' !oc! n&st,&tic $&nt* T,is is

&!in&d ". 'o!!o6in$ ,&no-&non*

22


23/31

ach-ph-la,is ( Is d&'in&d s n incr&sin$ to!&rnc& to dru$ t,t is d-inist&r&d r&&t&d!.*A!t,ou$, di''icu!t to &!in tc,.,.!is is ro""!. "rou$,t "out t,rou$, so-& or !! o' t,& 'o!!o6in$

'ctors &d&- !oc!i=&d ,&-orr,$& c!ot 'or-tion trnsudtion ,.&rntr&-i nd d&cr&s&d H o' tissu&s* t,&

'irst 'or- 'ctors iso!t& t,& n&r3& 'ro- contct 6it, t,& !oc! n&st,&tic so!ution* H.&rntr&-i ris&s t,& sodiu-

ion $rdi&nt t,us count&rctin$ t,& d&cr&s& in sodiu- ion conduction "rou$,t "out ". t,& !oc! n&st,&tic* T,& !st

'ctor d&cr&s& in H o' t,& tissu&s is "rou$,t "out ". t,& 'irst in'&ction o' t,& cidic !oc! n&st,&tic t,& -"i&nt

H in t,& r& o' in;&ction -. "& so-&6,t !o6&r so t,t '&3&r !oc! n&st,&tic -o!&cu!&s r& trns'or-&d into t,&

'r&& "s& RN) on r&in;&ction*

POTENTIATION OF ACTION OF LOCAL ANESTHESIAIt is co--on rctic& to o!d 3rious $&nts to n&st,&tic so!utions in ord&r to incr&s& t,& int&nsit. or

durtion o' ction*

VASOCONSTRICTORS ( T,& 3!u& o' 3soconstrictors in ro!on$in$ !oc! n&st,&tic ction ,s "&&n 6&!! &st"!is,&d* As r&su!t o' !oc!

3soconstriction t,& "sortion o' t,& !oc! n&st,&tic is d&!.&d nd t,& &''&ct o' t,& n&st,&tic is !!o6&d to continu&

t t,& !oc! sit&*

Ro!& o' 3soconstrictor in !oc! n&st,&tic so!ution is s 'o!!o6s

/ ?. constrictin$ "!ood 3&ss&!s 3soconstrictors d&cr&s& "!ood '!o6 &r'usion) to t,& sit& o' in;&ction*/ A"sortion o' t,& !oc! n&st,&tic into t,& crdio3scu!r s.st&- is s!o6&d r&su!tin$ in !o6&r n&st,&tic

"!ood !&3&!s

/ Lo6&r !oc! n&st,&tic "!ood !&3&!s d&cr&s& t,& ris# o' !oc! n&st,&tic toicit.*

/ Hi$,&r 3o!u-&s o' t,& !oc! n&st,&tic $&nt r&-in in nd round t,& n&r3& 'or !on$&r &riods t,&r&".

incr&sin$ t,& durtion o' ction o' -ost !oc! n&st,&tics

/ soconstrictors d&cr&s& "!&&din$ t t,& sit& o' t,&ir d-inistrtion nd r& us&'u! 6,&n incr&s&d "!&&din$

is nticit&d*

T,& ctions o' t,& 3soconstrictors so r&s&-"!& t,& r&sons& o' dr&n&r$ic n&r3&s to sti-u!tion t,t t,&. r&

c!ssi'i&d s s.-t,o-i-&tic dr&n&r$ic dru$s* T,&r& dru$ ,3& -n. c!inic! ctions "rid&s 3soconstriction*

S.-t,o-i-&tic dru$ -n. !so "& c!ssi'i&d ccordin$ to t,&ir c,&-ic! structur&*

I. /ccording tohemical structure :Catecola%!nes (

• Ein&,rin&• Nor&,in&,rin&• Do-in&• L&3onord&'rin• Isorot&r&no!

Non catecola%!nes

• A-,&t-in&

• M&t,-,&t-in&• H.dro./-,&t-in&• E,&drin&• M&,&t&r-in&• M&tr-ino!• P,&n.! &,rin&

II. /ccording to $odes of action :i) D!#ect ? act!n" $"s

T,&. &&rt t,&ir ction dir&ct!. on dr&n&r$ic r&c&tors*

• Ein&,rin&

• Nor &in&,rin&• L&3onord&'rin

2%

Ntur!


24/31

• Isorot&r&no!• Do-in&• M&t,o-in&• P,&.!&,rin&

ii) In&!#ect ? act!n" $"s

T,&. ct ". r&!&sin$ nor&in&,rin& 'ro- dr&n&r$ic n&r3& t&r-in!s*

• T.r-in&• A-,&t-in&• M&t,-,t-in&• H.dro.n,&t-in&

iii) Mi&d 0 Actin$ Dru$s

6it, "ot, dir&ct nd indir&ct ctions*

• M&tr-in!• E,&drin&*

ADRENERGIC RECEPTORS (T,& conc&t o' dr&n&r$ic r&c&tors 6s roos&d ". ,!uist in 18(7 nd is 6&!! cc&t&d tod.* Adr&n&r$ic

r&c&tors r& 'ound in -ost tissu&s o' t,& "od.* A,!uist r&co$ni=&d t6o t.&s o' dr&n&r$ic r&c&tors*

• A!, α)• ?&t β)

Acti3tion o' α r&c&tors cus&s 3soconstriction*α1 &cittor. 0 ost s.nticα2 in,i"itr. 0 ost s.ntic*

Acti3tion o' β r&c&tors roduc&s s-oot, -usc!& r&!tion 3sodi!tion nd "rondiodi!tion) nd crdicsti-u!tion incr&s&d ,&rt rt& nd str&n$t, o' contrctions)*

β1 Found in ,&rt nd s-!! int&stin&s nd r& r&sonsi"!& 'or crdic sti-u!tion nd !io!.sisβ2 'ound in "ronc,i 3scu!r "&ds nd ut&rus nd roduc&s "rondiodi!tion nd 3sodi!tion*

1ilutions of 'asoconstrictors:

T,& di!ution o' 3soconstrictors in co--on!. r&'&rr&d to s rtio*

D!l$t!on M"=%l Te#a,e$t!c $se

11999 1*9 E-&r$&nc. -&dicin& IMSc

n,.!is)

12+99 9*( P,&n.!&,rin&

119999 9*1 E-&r$&nc. -&dicin& I

crdic rr&st)

129999 9*9+ L&3onord&'rin

1%9999 9*9%% Nor&in&,rin&

1+9999 9*92 Loc! n&st,&si

179999 9*912+ Loc! n&st,&si

1199999 9*91 Loc! n&st,&si

12999999 9*99+ Loc! n&st,&si

&. +pinephrine

• Most ot&nt nd 6id&!. us&d 3soconstrictor in d&ntistr.• Sourc& 79@ o' -&du!!r. s&cr&tion !so 3i!"!& s s.nt,&tic• Mod& o' ction is "ot, nd " 6it, " "&in$ r&do-int&

S.ste%!c E''ects o' E,!ne,#!ne

• M.ocrdiu- /Incr&s& ,&rt rt& nd crdic outut

2(

Non ct&co!-in&s

?s&d on t,& in,i"itor. or &cittor. ctions o'ct&co!-in&s on s-oot, -usc!&*


25/31

• Pc&-#&r /Incr&s& ris# o' d.sr,.t,-i• Coronr. Art&r./Di!tion o' coronr. rt&r.• ?!ood Pr&ssur& /Incr&s&d s.sto!ic r&ssur& &''&ct on disto!ic r&ssur& is dos& r&!t&d• Crdio3scu!r /D&cr&s& crdic &''ici&nc.• scu!tur& /soconstriction in s#in -ucous -&-"rn& < #idn&.s /sodi!tion in s#&!&t! -usc!& in s-!! dos&s 3soconstriction in !r$& dos&s

• R&sirtor. / ?ronc,odi!tor • CNS / Not ot&nt CNS sti-u!nt• M&t"o!is- / Incr&s& o.$&n consu-tion

Te#%!nat!on o' E,!ne,#!ne

• R&ut#&• COMT nd MAO• Ecr&t&d unc,n$&d in urin& 1@)

Cl!n!cal Man!'estat!ons o' E,!ne,#!ne O/e#&ose

• CNS sti-u!tion / '&r ni&t. tr&-or !!or di==in&ss• Crdic d.sr,.t,-i• &ntricu!r 'i"ri!!tion• Drstic incr&s& in ?P / cn cus& c&r&"r! ,&-orr,$&• An$in in ti&nts 6it, coronr. insu''ici&nc.

Ma0!%$% Dose 'o# Dental A,,o!nt%ent

• Nor-! ,&!t,. ti&nt

9*2 -$* &r oint-&nt

• Si$ni'icnt crdio3scu!r i-ir-&nt 9*9( -$ &r oint-&nt

Cl!n!cal A,,l!cat!ons 'o# E,!ne,#!ne

• Acut& !!&r$ic r&ction• ?ronc,oss-• Crdic rr&st• H&-ostsis

• Produc& -.drisis• soconstrictor • Nor&in&,rin&

So$#ce( 29@ o' dr&n! -&du!! s&cr&tion !so 3i!"!& in s.nt,&tic 'or-

Mo&e o' act!on : !-ost &c!usi3&!. " &''&ct in ,&rt

2. orepinephrine

• 1( ot&nc. o' &in&,rin&

S.ste%!c E''ects o' No#e,!ne,#!ne

• M.ocrdiu- / incr&s& 'orc& o' contrction

2+


26/31

• Pc&-#&r / incr&s& sti-u!tion cusin$ d.sr,.t,-i• H&rt rt& / d&cr&s& ,&rt rt&• Coronr. rt&r. / incr&s& coronr. '!o6• ?!ood Pr&ssur& / incr&s& "ot, s.sto!ic nd disto!ic• Crdio3scu!r / incr&s& stro#& 3o!u-& d&cr&s& crdic outut• CNS / no &''&ct t t,&r&utic dos&s• M&t"o!is- / incr&s& "s! -&t"o!ic rt& incr&s& "!ood su$r

El!%!nat!on o' No#e,!ne,#!ne

• R&ut#&• COMT nd MAO• Ecr&t&d unc,n$&d in urin&

O/e#&ose o' No#e,!ne,#!ne

• S-& s &in&,rin&

• Cn cus& s!ou$,in$ o' tissu& du& to &''&ct

A/a!la*!l!t. !n Dent!st#.

• >it, -itur& o' rocin& nd roo.cin& in conc&ntrtion o' 1%9999

Ma0!%$%Dose'o# Dental A,,o!nt%ent

• H&!t,. ti&nt 9*%( -$* &r oint-&nt

• M&dic!!. co-ro-is&d 9*1( -$* &r oint-&nt

3. e'onordefrin

P#o,#!eta#. na%e / N&o/Co"&'rin

So$#ce( s.nt,&tic

Mo&e o' act!on / -ost!. 2+@ "

S.ste%!c act!on / s-& s &in&,rin& "ut to s-!!&r d&$r&&

Te#%!nat!on : COMT nd MAO

A/a!la*!l!t. / 129999 conc&ntrtion 6it, M&i3cin& or -itur& o' Proo.cin&Procin&

Ma0!%$% &ose 'o# all ,at!ents 1 -$* &r oint-&nt

. 4hen-lephrine 5-drochlorideP#o,#!eta#. na%e / N&o/S.n&,rin&

So$#ce ( s.nt,&tic

Mo&e o' act!on / 8+@

S.ste%!c Act!on o' Pen.le,#!ne H.oclo#!&e

• M.ocrdiu- / !itt!& &''&ct

• Pc&-#&r / !itt!& &''&ct• Coronr. rt&r. / incr&s& "!ood '!o6

24


27/31

• ?!ood Pr&ssur& / incr&s& s.sto!ic nd disto!ic• H&rt rt& / "rd.crdi• R&sirtor. / "ronc,odi!tor "ut not &''&cti3& 'or "ronc,oss-• CNS / -ini-u- &''&ct• M&t"o!is- / so-& incr&s& in -&t"o!ic rt&

Te#%!nat!on / ,.dro.!tion to &in&,rin&

Cl!n!cal a,,l!cat!on / 3soconstrictor ns! d&con$&stnt

A/a!la*!l!t. / 12+99 6it, (@ rocin&

Ma0!%$% Dose 'o# Pen.le,#!ne H.oclo#!&e

• Nor-! ,&!t,. ti&nt ( -$* &r oint-&nt

• M&dic!!. co-ro-is&d 1*4 -$* &r oint-&nt

Facto#s !n select!on o' Vasoconst#!cto#• L&n$t, o' t,& d&nt! roc&dur&• T,& n&&d 'or ,&-ostsis durin$ nd 'o!!o6in$ roc&dur&• T,& -&dic! sttus o' t,& ti&nt

Vasoconst#!cto# Facto#s to Cons!&e#

• Hi$, ?P Crdio3scu!r dis&s&• H.&rt,.roidis-• MAO In,i"itors nti/d&r&ssnt)• Tric.c!ic ntid&r&ssnts

• Pti&nt usin$ cocin&/n&3&r us& &in&,rin&

RECENT ADVANCES AND FUTURE TRENDS IN PAIN CONTROLT,rou$, !oc! n&st,&si r&-ins t,& "c#"on& o' in contro! in d&ntistr. r&s&rc, ,s continu&d in "ot,

-&dicin& nd d&ntistr. to s& n&6 nd "&st&r -&ns o' -n$in$ in ssocit&d 6it, -n. sur$ic! tr&t-&nts*

!) Cent*$c#!&!ne (It is uin!on& d&ri3ti3& 6it, 'i3& to &i$,t ti-&s t,& ot&nc. o' !idocin& nd 6it, n &u!!. rid ons&t

nd n &ui3!&nt durtion o' ction* Si$ni'icnt!. is do&s not &''&ct c&ntr! n&r3ous s.st&- or crdio3scu!r s.st&-

d3&rs&!. &c&t 6,&n d-inist&r&d in 3&r. !r$& dos&s*

It ,s "&&n us&d in su"rc,noid nd &idur! n&st,&si nd in intr3&nous r&$ion! n&st,&si*

c,r&;ni &t ! co-r&d t,& &''icc. o' 9*+@ C&nt"ucridin& conc&ntrtion 6it, t,t o' 2@ !idocin& 'or

d&nt! &trction in 129 ti&nts* T,&. r&ort&d t,t d&$r&& o' n!.sis ttin&d 6it, C&nt"ucridin& t,t co-r&d6&!! to t,t o"tin&d 6it, !idocin&* C&nt"ucridin& 6s 6&!! to r&!t&d 6it, no si$ni'icnt r-&t&rs nd no s&rious

sid& &''&cts* 6,&n d-inist&r&d to o3&rdos& C&nt"ucridin& 'unction s tru& sti-u!nt o' t,& CNS un!i#& !idocin&*

!!) Ro,!/aca!ne (It is !on$/ ctin$ -id& n&st,&tic si-i!r to "ui3cin& nd &tidocin& in durtion o' cti3it.* It is

structur!!. si-i!r to -&i3cin& nd "ui3cin& "ut is uniu& in t,t it is r&r& s iso-&r rt,&r t,n s

rc&-ic -itur&*

Dt indict& t,t it ,s $r&t&r -r$in o' s'&t. "&t6&&n con3u!si3& nd !&t,! dos&s t,n do&s "ui3cin&*

T,& &!i-intion !i'& o' roi3cin& is 2+*8 -inut&s 6,ic, is consid&r"!. s,ort&r t,n t,t o' ot,&r -id&s*

Roi3cin& ,s d&-onstrt&d d&cr&s&d crdio/toicit. r&!tion to "ui3cin& "ut its c!inic! durtion o' ction is

roi-t&!. 29@ s,ort&r*

T,& ri-r. us& o' roi3cin& in n&st,&sio!o$. ,s "&&n 'or r&$ion! n&r3& "!oc# &s&ci!!. &idur!)* Its ot&nti! 'or us& in d&ntistr. s not,&r !on$/ctin$ !oc! n&st,&tic &rs $r&t "ut 6its c!inic! &3!ution*

25


28/31

!!!) EMLA (Intct s#in is n i-&rious "rri&r to t,& &n&trtion o' dru$s inc!udin$ toic! n&st,&tics* Y&t onc& s#in is

d-$&d s occurs in sun"urn or in;ur. n&st,&tic dru$s suc, s so!rcin& cou!d "& !i&d toic!!. 'or t,& r&!i&' o'

in* For .&rs dru$ or t&c,niu& 6s sou$,t t,t 6ou!d &r-it n&&d!&s to "& ins&rt&d in!&ss!. t,rou$, intct

s#in* T,& d&3&!o-&nt o' oi!/in/6t&r &-u!sion continin$ ,i$, conc&ntrtions o' !idocin& nd ri!ocin& in "s&

'or- r&su!t&d in EMLA &ut&ctic -itur& o' !oc! n&st,&tics) 6,ic, ,s "&&n s,o6n to ro3id& n&st,&si o' intct

s#in ro'ound &nou$, to &r-it 3&niuntur& to "& &r'or-&d in!&ss!.*

EMLA consists o' +@ cr&- continin$ 2+-$$ !idocin& nd 2+-$$ ri!ocin&* It is !i&d to t,& s#in 'or

t !&st 1 ,our "&'or& t,& nticit&d roc&dur&* T,& cr&- is co3&r&d 6it, n occ!usi3& dr&ssin$* R&s&rc, ,sd&-onstrt&d t,& &''&cti3&n&ss o' EMLA in -n. s&cts o' &ditrics inc!udin$ 3&n&unctur& 3ccintion sutur&

r&-o3! !u-"r unctur& -inor oto!o$ic! sur$&r.* It is !so &''&cti3& in -inor $.n&co!o$ic! nd &co!o$ic!

roc&dur&s nd d&r-to!o$ic! sur$&r. inc!udin$ s!it/t,ic#n&ss ost ,&r&tic n&ur!$i d&"rid&-&nt o' in'&ct&d

u!c&rs nd in,i"ition o' itc,in$ nd "urnin$ in du!ts*

T,& ot&nti! 'or toic !oc! n&st,&tic "!ood !&3&!s d&3&!oin$ 6it, EMLA is -ini-!* P&# !s- n&st,&ticconc&ntrtions occurrin$ 179 -inut&s 't&r !iction ,3& "&&n uit& !o6* T,& us& o' EMLA in in'nts und&r t,& $&

o' 4 -ont,s is contrindict&d "&cus& o' t,& ossi"i!it. o' -&t"o!it& o' ri!ocin& inducin$ -&t,&-o$!o"in&-i*

Ad3&rs& r&sons&s not&d inc!ud&d trnsi&nt nd -i!d s#in "!&&din$ nd Er.t,&-*

S&3&r! studi&s ,3& r&ort&d on t,& intr/or! us& o' EMLA cr&-* EMLA d&cr&s&d ti&nt r&orts o' in

to n&&d!& ins&rtion nd n&st,&tic d-inistrtion si$ni'icnt!. in "ot, t,& $r&t&r !tin& nd nso!tin& in;&ction

co-r&d to !c&"o !iction* Ho6&3&r t,& us& o' EMLA in n tt&-t to o"tin Pu!! n&st,&si ,s ro3id&d

con'!ictin$ r&orts*

!/) ,H alte#at!ons (T,& d-inistrtion o' !oc! n&st,&tics into s#in nd to !&ss&r d&$r&& or! -ucous -&-"rn&s is 'r&u&nt!.

unco-'ort"!&* T,ou$, -n. 'ctors r& in3o!3&d in t,is inc!udin$ t,& s&&d o' in;&ction 3o!u-& o' so!ution d&nsit.

o' t,& tissu&s nd !ot o' s.c,o!o$. t,& cidic H o' t,& n&st,&tic so!ution !. si$ni'icnt ro!& in ro3o#in$disco-'ort durin$ !oc! n&st,&tics in;&ctions* T,& H o' !in !oc! n&st,&tic so!ution is roi-t&!. +*+

6,&r&s t,t o' 3so/r&ss&r/continin$ so!ution is "out (*+* T,& ddition o' su"stnc& to t,& n&st,&tic t,t

27


29/31

!#!ini=& t,& so!ution s,ou!d -#& t,& dru$s d-inistrtion -or& co-'ort"!&* in ddition t,& n&st,&tic dru$ t

,i$,&r H s,ou!d ,3& -or& rid ons&t o' ction nd $r&t&r ot&nc.*

T6o strt&$i&s ,3& "&&n us&d to c,i&3& t,is &''&ct t,& ddition o' sodiu- "icr"ont& to t,& n&st,&tic

so!ution nd t,& ddition o' cr"on dioid&* Cr"ontion o' !oc! n&st,&tics is not r&!!. n&6 t,&ir us& "&in$

d&scri"&d s &r!. s 184+*

T,& ddition o' sodiu- "icr"ont& to !oc! n&st,&tic so!ution i--&dit&!. rior to in;&ction !#!ini=&s t,&

so!ution incr&sin$ t,& nu-"&r o' unc,r$&d "s& -o!&cu!&s RN)* T,is unc,r$&d ionic 'or- is !iid so!u"!& nd

"!& to di''us& t,rou$, t,& n&r3& -&-"rn& 'or-u!tion o' !idocin& 6it, &in&,rin& !us sodiu- "icr"ont& H

5*2) ro3id& -or& rid ons&t o' n&st,&tic "!oc# ons&t Q 2 -in) t,n co--&rci!!. r&r&d H (*++) !idocin& !us &in&,rin& ons&t Q + -in)* Ho6&3&r i' t,& H o' t,& so!ution is too ,i$, !oc! n&st,&tic 6i!! r&ciitt& out s

t,& dru$ "s& t,&r&". d&cr&sin$ t,&ir s,&!' !i'&*

A!#!ini=tion o' &in&,rin& r& n&st,&tic so!ution ro''&rs no "&n&'it* R&co--&ndtion 'or r&rtion o'

t,& !oc! n&st,&tic 6it, "icr"ont& 't&r di3id&d "&t6&&n rt (*2@ "icr"ont& 6it, 19 rts !oc! n&st,&tic nd 1

rt 7*(@ "icr"ont& in + rts !oc! n&st,&tic*

Cr"on dioid& &n,nc&s di''usion o' !oc! n&st,&tic t,rou$, n&r3& -&-"rn&s ro3idin$ -or& rid ons&t

o' n&r3& "!oc#* As Co2 di''us&s t,rou$, t,& n&r3& -&-"rn& intrc&!!u!r H is d&cr&s&d risin$ t,& intrc&!!u!r

conc&ntrtion o' c,r$&d ctions RNH) t,& 'or- o' n&st,&tic t,t ttc,&s to r&c&tor sit& in sodiu- c,nn&!s*

Sinc& t,& ctionic 'or- o' t,& dru$ do&s not r&di!. di''us& out o' t,& n&r3& t,& n&st,&tic "&co-&s conc&ntrt&d

6it,in t,& n&r3& trun# t&r-&d ion trin$ ro3idin$ !on$&r durtion o' n&st,&si*

T,& ro"!&- c!inic!!. ,s "&&n t,t o' t,& cr"ont&d n&st,&tic $&nt is not in;&ct&d !-ost i--&dit&!.

't&r o&nin$ o' t,& 3i! t,& Co 2 6i!! di''us& out o' so!ution si$ni'icnt!. di-inis,in$ t,& so!utionBs &''&cti3&n&ss*T,& n&st,&tic dru$ -ust "& d-inistrt&d 6it,in s,ort ti-& 't&r r&rin$ t,& s.rin$&*

/) H.al$#on!&ase (,.!uronids& is n &n=.-& t,t "r&#s do6n intrc&!!u!r c&-&nt* It ,s "&&n d3oct&d s n dditi3& to

!oc! n&st,&tics "&cus& i' &r-its in;&ct&d so!utions to sr&d nd &n&trt& tissu&s*

T,& ri-r. us& o' ,.!uronids& ,s "&&n in !stic sur$&r. d&r-to!o$. nd o,t,!-o!o$ic roc&dur&

ri-ri!. in r&t&ro "u!"r n&r3& "!oc#s 6,&r& it ,s "&&n d&-onstrt&d to s&& "ot, t,& ons&am

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