‫بسم ال الرحمن الرحيم‬

Introduction:
• The references for this lecture are the record,&the slides
• The Dr announced in this lecture that every student have to search about
the mechanism of action of chlorhexidine as bactericidal& the reasons of
discoloration that caused by its use,and this homework will be part from
your quiz mark.
• All underlined informations are copied from the slides
• L.D.D.D stands for local delivery drug device,GCF :gingival crevicular
fluid,CHX MW:chlorhexidine moush
..………………………………………………………………………Now let's start
As we know periodontal diseases are initiated by bacteria (dental plaque) and
from this point of view we use antibiotics in the treatment of the periodontal
,diseases
Last time we talked about systemic chemotherapeutic agents specialy
antibiotics ;today we will continue talking about local application of
.antimicrobial agents

(Local delivery drug device(L.D.D.D

Any dental instrument that used to deliver drugs localy under certain rules(we
will see later),this is very important concept so if you want to practice
. periodontics your treatment will be much more selective for certain cases

Periodontal diseases comprise a group of chronic inflammatory disorders with

bacterial etiology that results in breakdown of the connective tissue

Safe & intrinsically efficacious medications can be delivered into periodontal

pockets to suppress or eradicate the pathogenic microbiota or modulate the
inflammatory response as we can give our pt systemic antibiotics to treat
periodontal diseases we can also safely introduce antimicrobial agents inside the
. deep pockets and this is what we want to concentrate on in this lecture

Local vs systemic application of antimicrobial agents

:Advantages of local antimicrobials

1
More concentration :the most important advantage of the local application√
of antimicrobial agents ,I can provide high concentration without any side
effect ,coz as we know the problem with systemic antibiotics in the treatment
of periodontal diseases as an adjunct to scaling and root planning is that we
are limited with concentration that reach to the base of the pocket via serum
or via the GCF and this concentration inspite that it is effective in reducing or
killing bacteria but it does not reach concentration beyond 12µg/ml which is
very low concentration but in LDDD we can provide very high concentration
of the antimicrobials inside the periodontal pocket For effective periodontal
.treatment by antimicrobial agents, there is a need for a high conc
.

. fewer side effects:we can avoid S/E that assosciated with systemic antibiotics√

substantivity:you can not benefit your pt from this property if he takes the√
antibiotic systemicaly ,but local application and binding or adsorbing to the
mucosa or the root of the tooth and then it will be elaborated to the pocket
when the concentration of the free antibiotic getting reduced. Some of them
including TET.s & CHX pocess this important property which is substantivity

Pt compliance : pts are more compliant with this sort of antibiotic delivery√
.than with systemic antibiotics
And finally there is
. NO risk of bacterial resistance as with systemic antibiotics √

:the disadvantages of local antimicrobials

 more chair side
more expensive
 No effect on bacterial reservoir :this means that for certain periodontal
diseases such as aggressive periodontitis the bacteria resides deep in the
gingival connective tissue and these sites can not be reached by local
application of antibiotics, its only can be reached by serum through systemic
. administration
Now the rules for local application of antimicrobial agents for the treatment of
:periodontal diseases are
The medication must reach the intended site of action:this site in our .1
. case in the periodontal treatment is the base of periodontal pocket
:Remain at adequate concentration .2
Last for sufficient duration of time.3

2
Any device that achieve the above 3 rules we can consider it as LDDD
. for periodontal treatment
In the past &till now in the practice periodontists are using
some methods thinking they are using LDDD for
example:many dentists and periodontists take CHX MW pull it
by hypodermic syringe ,bend the needle ,insert the needle
alittle bit in the periodontal pocket and inject the material and
this is called SUBgingival irrigation ,this method could achieve
the 1st point which is reaching to the intended site of action &
it might achieve the 2nd point which is I provide the area with
high concentration BUT it does not achieve the 3rd point which
is sufficient duration WHY …………….we will see why………………
((the answer is alittle bit long

: 1st we will talk about the importance of the 1st two rules
Site of action: Bacteria residing in periodontal pocket Soft tissue walls
of the pocket ,The exposed cemetum or radicular dentin all of these
areas have bacteria and their products that need to be reached locally
but not all antimicrobial agents can reach these areas ,such as mouth
:rinses &supragingival irrigation ,very nice illustration in slide #8

There are many devices in the markets saying that you can use
some sort of SUPRAgingival irrigation as aiding in mechanical
plaque control,but these devices are used wrongly in SUBgingival
irrigation and applied to the pocket as L.D.D.D by some dentist
3
In this slide starting from upper left picture ,as you can see(I hope
you can!!!)(supragingival irrigation) can reach from 29-71%of the
gingival sulcus (no deep pockets but there is gingivitis) and that is
why using CHX MW in the treatment of gingivitis as an adjunct to
scaling is very effective,now if you treat deep periodontal pocket
with SUPRAgingival irrigation it will not reach more than 65%of the
depth of the pocket (upper right picture)and our site of action is the
base of the pocket,also if you use these antimicrobials for
SUBgingival irrigation it will not reach more than 70-90%of the
depth of the pocket also not effective for the same reason –90%is
deep enough but we will see later what is the wrong with this-(lower
right &left picture),finaly the most right picture shows how using of
mouth rinses (as mouth wash not for irrigation) in the deep
periodontal pockets is useless ,not more than 4%of the pocket
depth and this is nothing (so you can not prescribe CHX MW in the
treatment of active,destructive periodontal diseases with deep
pockets as an adjunct to scaling and root planning coz it is simply
can not reach more than 4%of the pocket BUT IF YOU PRESCRIBE IT
TO HELP THE PT TO PRACTICE GOOD MECHANICAL PLAQUE
. CONTROL SUPRAGINGIVALY THEN IT IS OKAY
Back to subgingival irrigation using as we said hypodermic syringe
&needle with antimicrobial agents may reach depth of 90%of the
pocket BUT there is something called periodontal clearance ,it
means GCF replaces itself 40 times each hour which means if you
provide the area with some concentration it will be the half of its
beginning after 1 hour (I don't know how!!)due to continuous clearance
.of GCF inside the pocket
So you need a certain reservoir,certain material that maintains
inside the periodontal pocket continuously despite of periodontal
clearance this point can not be achieved by subgingival irrigation
,so the devices that are present in the markets as L.D.D.D are not
MW neither liquids inserted in the periodontal pocket ,but they are
the materials that achieve the 3 rules of L.D.D.D and containing
. substantive materials
:Now what is the definition of L.D.D.D
L.D.D.D. : consists of a drug reservoir and a limiting element that
controls the rate of medicament release
The goal is to maintain effective conc. of chemotherapeutic
agents at the site of action for long periods, despite drug loss
from G.C.F. clearance
4
according to the duration of medicament release )we can classify )
L.D.D.D into 1.duration less than 24 hours( Sustained release
(devices
(duration exeeds one day.(Controlled delivery devices.2 &

We are seeking for a device what we call it CONTROLLED local drug

delivery device in which it gives us the effective concentration of
.the drug inside the pocket for more than 24 hours

These are generally the delivery

systems with regulatory approval by the ( FDA ) or the
regulatory bodies of the European Union
At present 5 products are commercially available
Tetracycline fibers (Actisite®, Alza corp., Mountain view,
(.C.A
Metronidazole gel ( Elyzol®, Dumex, Copenhagen,
( Denmark
(.Minocycline gel (Arestin®,Lederle,U.K
(®Chlorhexidine chip (Periochip
Doxycycline hyclate in a resorbable polymer (Atridox®,
Collines, Co.)we mention the companies coz they are the only companies that
.produce these products
Notice that 4 of these5 antimicrobial agents have substantivity
property (tetracyclines &CHX)and the other metronidizole is for
. its anaerobic action

Before we talk about each one separately it is very important to

??know when &where I use L.D.D.D
Not every pt after you finish examination you provide him with
L.D.D.D,there is role of application coz as we said it takes more
chair side &it is very expensive (the syringe of atridox costs
:200$)so

Role of Local Delivery of Antimicrobials

Localized sites of inflammation associated with PD> 5mm
that did not respond to S&RP and are not eligible for
surgery

5
Localized sites of inflammation associated with recurrence
or persistence of PD > 5mm in maintenance patients(deep
(pockets with bleeding on probing

Surgery is unpredictable or undesirable

Used as an adjunct to mechanical therapy and not as a

substitute

1st one that we will talk about is tetracycline fibers(you will see why
(these fibers are not used any more in the practice
®actisite
Non resorbable cylindrical L. D.D.D. made of –
. a biologically inert,plastic copolymer
loaded with 25% Tetracycline. HCL powder.(very
high concentration 1300 times the concentration
(provided by systemic capsules
The fiber is applied to completely fill the pocket
Maintained in situ with a cyanoacrylate adhesive for 7 –10
(days, conc. excesses 1,300 ug/ml .(slide 14

???????????????BUT why this material is not used any more

first :Some pts are not compliant with the dentist or the
periodontist and do not come to remove the non-resorbable fiber
after 10 days ,so they will experience periodontal abcess coz
.(empty fibers are forign body (the most important reason
Second:due to the high concentration of the tetracycline in these
fibers some pts may experience fungal infections when they have
. more than 4 sites provided by tetracycline fibers
Now with the most effective L.D.D.D &has the best research
: studies&clinical results is
:Atridox
doxycycline hyclate gel(very high concentration equal to 10%
(1000 times the conc. provided by the capsules
This gel consistency is the resorvire that we talked about
Mixed and Injected into the site it takes the shape of the
pocket
Continued release for 7 days
Biodegradable it will resorb by itself
6
:Needs training but relatively simple to use
It comes in the form of two syringe one of them contains the
powder and the other contains the liquid then the components
will be mixed together in a certain way –that funny way!!-until the
mix become in the gel form then you insert it in the pocket until
you see the pocket slightly swollen then you should provide the
orifice of the pocket with some sort of glue to prevent the
material from slippage out ,then you examine the pt after two
week to see the results ,and very important to remember that you
. should apply the gel after scaling &root planning

Periodontal clearance will not affect this process ,coz this gel
contains high conc. of the antimicrobial agent ,even with
.periodontal clearance ,and the substantivity very high for atridox

Now(slide#17) this is a case that came to the Dr clinic ,was

diagnosed with aggressive periodontitis,after the Dr has treated the
pt with scaling &root planning ,there is still some areas with severe
recession, deep pockets &bleeding on probing which means that the
disease is active in the maintenance phase, the Dr can not provide
her with any sort of periodontal surgery coz it will make the
recession longer ,then atridox was applied inside the pocket ,as you
see in( slide #18)the pocket is slightly swollen,then we place
adhesive material(cyanoacrylate) at the orifice of the pocket so
when you apply L.D.D.D correctly to where it should be applied you
.(will have 100%success rate(slide 19 afetr atridox ,upper picture

: Another type of L.D.D.D provided in the markets is

Arestin
Is a bioabsorbable sustained delivery system consisting
: of
Minocycline HCL in a matrix of Hydroxyethyl ( 2% )
cellulose
(Amino alkyl methacrylate(as adhesive
Tryasitian & glycerin Magnesium chloride is added to
modify the drug release properties
Bacteriostatic antibiotic , no data regarding the period of
it’s reservoir
:the Dr read what is written in the pruchore of this drug
:Clinical use
7
Periodontitis with pockets >= 5 mm(and sure that don not
(respond to scaling &root planning and not eligible to surgery
:How supplied
Box containing 2 trays each containing 12 cartridges

Cartridge contains 1 mg of minocycline (semisynthetic

tetracycline derivative) microencapsulated in Poly dry
powder

Cartridge inserted into a cartridge handle

:Mechanism of action
Broad spectrum
Bacteriostatic
G.C.F levels maintained at high levels for at least 14
days
As you see in slide #23,figure 1 snap,figure 2 inject the material
,(inside the pocket(it comes as spheres of gel
:Another type is

(®CHX chips(periochip

As we all know the concentration of CHX MW is 0.2%,imagine that

the concentration of the CHX in the biodegradable chips is
.(2.5mg (very high concentration

Used only in pockets > 5 mm

Insertion could be challenging, it should be gently pushed

into pocket
.In slide #25 this is periochip kit ,each kit contains 10chips
Due to its shape &width it can not be inserted at any pocket(look
slide#26)it needs pockets with large width to be inserted in,
(slide#27)in this slide there is wide pocket with missing adjacent
.tooth suitable for CHX chips
Very delicate chips when it get alittle moisture it will shrink by
itself,so you should train yourself very will to apply it immediately
.in its correct position
Q:CHX is not an antibiotic ,so how we use it to kill bacteria in the
???deep pockets

8
Dr:it is an antimicrobial-MOA is homework-mainly bactericidal it
can kill bacteria inside the pocket ,but you can not kill this
bacteria using CHX MW coz as we said it can not reach more than
.4%of the pocket depth,and in low conc.0.2%
:Now we have finished L.D.D.D and we will talk about CHX MW
Forms: digluconate , acetate and hydrochloride salts.the 3
first two are water-soluble
Palque inhibition was first investigated in 1969 by
Schroeder
The definitive study was by Loe& Schiott 1970: showed
that rinsing with 10ml of 0.2%(20mg dose) twice daily in
absence of normal tooth cleaning inhibited plaque
regrowth and development of gingivitis

As you see in slide #29 this the form of

CHX
Bisguinide antiseptic
Strong base & dicationic at pH above 3.5 ◊ extremely
interactive with anions(as you know cations are +ve&anions
(are –ve
Minimally absorbed through skin or mucosa◊ no systemic
toxicity
Can cause neurosensory deafness if introduced into the
middle ear
Has a broad antimicrobial action,G+ve & against some
fungai & yeast as candida ,and against some viruses
including HBV & HIV
No reported bacterial resistance with long term use

Chlorhexidine/ Side effects

Brown discoloration of teeth,dorsum of tongue and
restorative materials( staining of the teeth is exogenic can be
removed by scaling & polishing and this stainig has a certain cause
and part of this cause depend on your instructions of use that you
give to your pt ,you should instruct the pt to rinse 30 mins after
brushing not immediately and not to eat or drink for 30 mins), In
slide #32 you can see brown discoloration of the teeth &the
. tongue
Taste perturbation mainly salt taste◊ bland taste
(Oral mucosa erosion(slide 33 pic.on the left side
9
Unilateral or bilateral parotid swelling???(pic. On the right
(side
?Enhanced supragingival calculus formation
Has a bitter
taste

CHX FORMS
Mouthwashes: 0.2,0.1 and 0.12%
use 15ml 0.12% equal to 10 ml 0.2%
Gel: must be delivered to all tooth surfaces
.Sprays: for physically or mentally handicapped
Toothpaste :difficult to formulate
Varnish: for root caries prevention

Chlorhexidine/ uses
As the dr noticedc that we prescribe CHX MW haphazardly in the
:clinic,so he said that we should know these indications very well
Adjunct to OH and professional prophylaxis(the most
(important
Postoral surgery
Jaw fixation
Mentally and physically handicapped
Medically compromised predisposed to oral infections
High-risk caries
Recurrent oral ulcerations
orthodontics appliance
Denture stomatitis
Immediate preoperative rinsing
Subgingival irrigation

Chlorhexidine/conclusions
Chlorhexidine to date is the proven most effective
antiplaque agent for which commercial products are
available to the public(so any new MW when you want to make
certain study on it either you test the material with placebo has
the same color ,taste,shape of the new product if the new product
gives better results then I consider it as more effective than the
placebo!but this is not enough to say that this product is effective
against gingivitis and plaque accumulation,the research says that
10
you should test it with another material-positive control-which is
. CHX MW
Chlorhexidine is free from systemic toxicity in oral use,
and microbial resistance and supra-infection do not occur

Local side effects are reported which are mainly cosmetic

problems

The antiplaque action of chlorhexidine appears dependent

on prolonged persistence of antimicrobial action in the
mouth (substantivity

A number of vehicles for delivering chlorhexidine are

available, but mouthrinses are most commonly
recommended

Extrinsic dental staining &perturbation of taste are

variably the two side effects of chlorhexidine mouthrinse
usage which limit acceptability to users and the long-term
employment of this antiseptic in preventive dentistry

:Finaly we will talk about tooth paste

The Dr said that We should know the components of tooth paste,coz
your answer for the next week homework why I should not give CHX
MW immediately after brushing?which means that there is certain
ingredients in the tooth paste that counteract the action of CHX
………MW……search more about
In slide #41 you can see why some tooth pastes come striped with
different colors …..coz it is coated from the inside with the green or
red material…and the white material in the middle so when the TP
.squeezed two colors will exit from the tube

Benefits of toothpastes
:The Dr read them from the slides
Caries control

Fluoride is available in a range of concentrations 250-

.2800 ppm
F]≤ 600ppm → children ≤7years with low caries]
.incidence

11
F] =1000ppm → children ≤7 years with high caries]
risk
.F]1000-1500ppm → all individuals 7 years and above]
F]2800ppm→ high risk adults and elderly]

Gingivitis and :
periodontitis
Triclosan is the most widely used antimicrobial
It also has anti-inflammatory properties &thus could
reduce gingival inflammation independent of its effect on
plaque

:Dentine sensitivity
Strontium chloride 10%
Potassium nitrate
Potassium citrate
Stannous fluoride

Anti calculus))Anti-tartar
Soluble pyrophosphate
Zinc salts
Triclosan

Whitening
The main action is through abrasive removal of
extrinsic stains
Whitening toothpastes

Abrasives
Macleans whitening, colgate platinum
Oxidizing agents
Brilliant whitenning system,Rapid white
Enzymes
Rembrandt original
Detergents
.Aquafresh whitening
EDTA
Boots advance white

: Tooth tips

12
Choose a toothpaste that is fluoridated,
brush for 2 minutes at least twice daily

Studies suggested that bacteria regrow on clean teeth

about 4 hours after brushing -> brush and floss regularly

The mechanical action and the technique of brushing are

much important than the brand of the toothpaste
The most common question the pt will ask you about the best
type of tooth paste that he/her should use ?your answer should
be that the name of the brand is not as important as the
technique of brushing UNLESS your pt want the TP as vehicle of a
medication (CHX,fluoride ,desensitizing agent…..etc)then you
.should recommend your pt with the suitable type
conclusions

Current data suggest that L.D.D of antimicrobials into a

periodontal pocket can improve periodontal health
Monotherapy with them is questionable , adjunctive use
of L.D.D.Dmay enhance the results in sites that don’t
respond to conventional therapy
L.D.D.D. should only be used in specific areas were
conventional forms of therapy may fail to control infection
So it should not be used routinely in situations when
efficacious results can be accomplished with S&RP

The end
Your colleague:Heba.A.Ali

Special thanx to AaAyYaA & S7R for help

.……………………Good luck in the exams

13