‫بسم ال الرحمن الرحيم‬

Chemotherapeutic agents
Introduction:
• Today’s lecture will be the last lecture in the preventive aspects
•
What the Dr wants us to get from this lecture is using clinical
applications in the peado clinics ,and start to implement these
agents in our tt plans from now on
•
Fluoride is considered from the chemotherapeutic agents but
since we’ve covered it in previous lectures we will not mention it
here .
We will talk about four types and they are: CHX,Xylitol,CPP-ACP, and
vaccination .

So lets begin……………………………

CHX(chlorohixidine):
 CHX gluconate is a salt

At ph 7 it dissociates –coz it is a salt-to give +ve charged
molecules
 Products(how its found in the markets )
0.2% CHX as Savacol and plaqacid
0.12%CHX as diffalm,dental solution,savacol freshment ,and peridex

What Dr wants us to know not the products names but that CHX
is available in different concentrations

Its activity comes from the electrostatic interaction with and
consequent impairment of the –ve charged bacterial cell
membrane –coz its +ve charged-
At high concentrations CHX induce coagulation of cytoplasmic
membrane of the bacteria and cell death .
So CHX might be bactericidal or bacterostatic :
Bactericidal at high concentrations and bacterostatic at
low concentrations , but generally we can consider it as
bactericidal agent
We,ve many forms of CHX ………………..

First:CHX mouth rinse :

an example on savacol mouth rinse …………………………………

Savacol Mouth Rinse

regular freshmint
CHX 2 mg/ml2 CHX 1.2 mg/ml 1

Rx: 10 ml for 1 min 15 ml for 1 min


For the 1st type (regular type)0.2%CHX instruct your
patient to rinse by 10 ml for 1 whole minute to get the total
effect (very important )

The patient should use them straight away without dilution
coz dilution will decrease the effect of CHX

For the 2nd type (freshmint type)0.12%,coz it is less
concentrated instruct your patient to use more than 10ml
(nearly 15 ml)to get the same effect .

Second:CHX gel:

 New form of CHX


The problem with CHX mouth rinse _which doesn’t
consider as a problem for normal healthy people _is it
contains alcohol ,these amounts of alcohol will irritate oral
mucosa of cancer therapy patients ,which already have
mucositis from radiotherapy .

So the indications for CHX gel use are cancer patient
receiving radiotherapy and other use is for very young
 children who can’t rinse and with high caries risk so simply
they can put CHX gel on tooth brush and brush their teeth .

Charachteristics of CHX gel:

 No alcohol ,no irritation to the mucosa
 Imperceptible taste during use
 Very slight after taste from sustained release (so children
accept its taste more than CHX mouth rinse)
 Intermittent use gives no staining (unlike mouth rinse which
causes reversible staining)
 Exellant patient compliance
 Low cost
 Used once weekly coz its concentration is high (1%)to
achive suppression of cariogenic bacteria
 Used for infants ,children ,and older patents (no age
constrictions )

60 seconds of tt causes reduction in MOs with
recolonization to base lines within 4-6 weeks .
They started with children at early age and got them to use CHX
gel for 6 months then they found that MOs was reduced to the
baselines and after they stopped the tt MOs returned back to its
levels .
So if you are not using good measures of oral hygine all the time
MOs will easily return back ,coz there is no agent has permanent
effect .

Third :chlorofluro gel:

 CHX 0.2%and NaF 0.003% combined together in the same
product to get the bactericidal effect of CHX and the
remineralization effect of fluoride
 Ions neutralize each other
 There is a study says that it's less effective than using CHX
alone.

by now we have finished CHX forms

Now we will taik about…..
Effects and advantages of CHX(rinse and gel):
 bactericidal:reduces dental plaque

reduces discomfort of mouth ulcers:if you get a child

with mouth ulcers (apthous ulcers )CHX –either the gel or rhe
rinse form –is very effective ,mother can put CHX gel on the
child’s tooth brush and brush his teeth or if the gel is not
available CHX rinse can be used (better than nothing)
staining of teeth :this staining is reversible ,so always
reassure the parents that there will be staining and its reversible
will disappear by tooth brushing or prophylaxis by rubber cup
and prophy paste or pumic

exellant compliance

low cost

ability of CHX to adsorb to anionic substances :for

example hydroxyl apatite,pellicles ,salivary GPs ,MMs and
polysaccharides coats of bacteria.
So that is why we use it for mouth ulcers ,coz it still
affecting even after patient rinses after few hours

slow release gives prolonged anti-bacterial effect

(substantivity)

 80% reduction in dental plaque when used as

adjunct in oral hygine :so it is very effective as long as you still
using it .
Dr said that there is false belive seen in the public that using CHX
mouth rinse is a replacement for tooth brushing ,it is important to
know that mouth rinse doesn’t remove plaque ,plaque has to be
removed physically then you can use the CHX and get the extra
 effect ……..so you can’t use mouth rinse as a replacement
for tooth brushing

student question which I couldn’t hear but it was about the

effect of CHX mouth rinse staining on newly placed composite
fillings ?Dr answered that composite can be stained by
coffe,tea,and other stains and CHX IS NOT THE ONLY
WORRY and you can polish composite if it get stained!!!

The documented uses of CHX in plaque control:

Documented means that they are evidence-based or based on
studies .
 Caries prevention
 Physically and mentally handicapped patients ,coz these
patients needs extra care

In high risk caries patients with medical history ar dental
history

Removable dentures and fixed orthodontic appliances
 Others,denture stomatitis (c.albicans ,post surgery,adjunct
to mechanical tt in perio scaling ,recurrent oral ulcers and
after traumatic injuries)

It would be nice when you start your ortho clinics in the 5th year and
deliver appliances to ur ptns to prescribe CHX or flouride mouth rinse
to prevent the high caries risk ,but i(Dr)am sure when you go to the 5th
year you will forget about this,and you wil be sending ptn to my clinic
with caries ,you also will fix and put the appliance on caries i(Dr)ve seen
this many times ,so you shouldn’t start an ortho tt before you restore
the teeth coz you will increase the caries risk .

 before a course of CHX is started all dental plaque and

calculus must be removed to allow the drug a fair start
What does that mean?
If patient comes to your clinic with multiple deposits of dental
plaque and very poor oral hygine ,it is good to begin scaling for
him ,clean the teeth then prescribe CHX for him and give OHI
to be applied at home .

Actions:

Bactericidal: cationic means +ve charged so binds –ve charged
MOs cell walls- especially the one that concern us the aciduric
type (S.mutans and Lactobacilli)-and changes the osmotic
equilibrium ,finally cell death

Anti-plaque :binds anionic acid groups of salivary GPs thus
decreasing pellicles formation and plaque colonization ,it binds to
salivary bacteria and prevents adsorption to the tooth .

the last thing about CHX we will taik about……..

side effects:
 staining:yellow brown staining on the gingival ½ and
interproximal sites ,stains can usually be removed by tooth brushing
with conventional tooth paste

 dulling of taste: it makes you hard to feel the taste of the food
after you use it

 increase calculus formation:(not fully understood)

 Desquamation :coz it contains alcohol the superficial epithelial

cells might be desquamed.

Xylitol

A non cariogenic sugar as it is cannot metabolized by
cariogenic MOs:remember that S.mutans have its high virulence
coz it can take sugar (glucose)and turn it into lactic acid by glycolysis
,when you come to xylitol the cell cannot make use of xylitol,it does
enter to this reaction but it doesn’t end up by lactic acid


A non sugar(not glucose) sweetner mass produced
principally from sustainable xylan-rich hard wood sources
such as birch and beech wood


Chemically ,it is a pentitol,which is a 5-c polyol ,it differs
from other polyols (e.g.sorbitol,mannitol )which contain a 6-
c ring

Charachteristics:
 A non cariogenic

In chewing gum it is anti-cariogenic reduces caries by
93%
They used xylitol in chewing gum and gave it to patients to chew ,then
they checked S.mutans rates and they found 93%reduction in the MOs
levels .BUT there was another explanation to what have been happened
,it might be due to xylitol plus the chewing process ,when you chew
gum you get all the food debris,plaque removed and washed away ,coz
chewing process increases salivary rate ,so chewing process plays a big
role in this case ,so it is related to chewing process rather than the gum
sweetners(as the Dr said)

 Inhibition of mother/ child transmission of cariogenic

MOs leading to reduced caries development
They gave the gum to pregnant mothers(coz children always get
bacteria from their mothers) some of which have young children, and
then they came back after a few years to see the results… they found 71-
74% caries reduction in 5 years old children. They compared it with F
& CHX control groups after regular maternal use of Xylitol for 21
months (when children where 3-24 months) & they didn’t chew gum or
use Xylitol products during the study period. The explanation for this is
that maternal use of Xylitol had affected children's probability of being
colonized by S. mutans.
It is well-known that the more you delay the aquisition of S.mutans the
less is the caries risk, coz as these bacteria establish themselves early in
life they will becom stronger and more resistant

 It is considered more effective in caries reduction rather

than sorbitol and mannitol
in this study they compared xylitol with other non cariogenic sweetners
and they found that xylitol is the most effective and this is called terquer
studies!! (sorry I am not sure)


Xylitol may be used in the preventive programs to reduce
caries.

“probably from now on when you write your tt plan in the clinic you
can include xylitol chewing gum within your preventive regimin like
CHX mouth rinse and fluoride gel ,you can advice the pnt to use CHX
mouth rinse at morning and fluoride gel befor going to sleep “Dr said

Xylitol chewing gums are available in the markets under different

names (Extra,wregly’s……..)fe nas 7ko 3lkt sh3rawi !!!!!!2keed l2 ya
s7r!!!!!!!

Disadvantages:
 the biggest disadvantage of xylitol is their liability to cause
osmotic diarrhea if eaten in large amounts .
For xylitol little discomfort is experienced with intakes of
about 20g per day although threshold should be lower for
children

Actions:
 
On plaque :it is non fermentable by MOs (will be explained
later),so it reduces plaque quantity( by chewing)and bacteria ,it
renders the produced strains with reduced virulence and it
participates in futile metabolic cycle also it reduces the
adhesion of plaque flora so reduces the transmission of bacteria


On saliva:it changes the quality and the quantity of saliva the
quantity will increase and the quality it will become more
flowable and watery (that is what we want) so you can use it for
xerostomic patients to increase their salivary flow and decrease
their caries risk


On enamel: it aids in remineralization of enamel .

Now we will taik about :

Xylitol mechanisms in reducing MOs:

 Non specific mechanisms:

Coz it is not fermentable ,it doesn’t encourage bacterial growth

 Specific mechanisms:
 When MOs exposed to xylitol they develop mutan –xylitol
resistant strains (coz of mutation)and this strain is less
virulent .

Increase in concentration of amino acids and NH4+
(alkaline)in plaque will neutralize plaque acids .
 It can act in a bacterostatic way ,some streptococci take up
xylitol -5-p resulting in the formation of intracellular
vacules and degradation of the cell membrane .

Xylitol can cause the futile metabolic cycle (useless cycle),it
enters the cell and exits the cell without anything happening
to it ,so streptococci take xylitol phosphorylate it to xylitol-
5-p then splits it by the action of phosphatases to phosphate
and xylitol and then xylitol is expelled outside the cell ,what
did the cell gain ?nothing ,looses its energy for nothing !
Casein phosphopeptides(CPP):
CPP is the tooth mousse ,it is available in the DTC and it costs 8JD for 1
tube !it comes with different flavours ,prof.Eric Reynold was the one
who reached the formula of CPP ,it contains Ca and P .
RecaldentTM :is the chewing gum form of CPP
Tooth mousse:is the cream form of CPP.
So the original product is CPP-ACP(casein phosphopeptide amorphous
calcium phosphate )
What do mean by amorphous ?this word is very meaningfull to indicate
that Ca and P are not bound together (in the ionic form)and this is
important coz you want Ca and P to be adsorbed to the tooth surface .
 Each molecule of CPP binds 25Ca ,15P and 5F ions .

CPP is derived from the casein, part of the protein found in the
cow’s milk

CPP increases levels of Ca and P up to 5 folds in human in situ
caries models and short term mouth wash studies .so by
application of tooth mousse on the tooth surface it increases the
levels of Ca and P in the saliva 5 folds

The proposed mechanism of their anticariogenicity is that they
act as a calcium-phosphate reservoir, buffering the activity of free
Ca & P ions in the plaque fluid helping to maintain a state of
supersaturation(after increasing levels of Ca and P in the saliva 5
folds they maintain this supersaturation by preventing them from
binding together coz of the high affinity of Ca and P ions toward
each other )with respect to enamel mineral,theraby depressing
enamel demineralization and enhancing remineralization


CPP have the ability to bind & stabilize Ca & P in solution &
bind to dental plaque & tooth enamel. i.e., it prevents P & Ca
from uniting together it keeps them in the amorphous non-
crystalline state which is the best state in means of absorbing
minerals by enamel. CaP is normally insoluble & non-absorbable
by enamel.
 
The  concentration of P & Ca ions in plaque was proven to
reduce demineralization & promote remineralization of enamel.


As we said Recaldent TM is the chewing gum form of CPP-ACP ,it
is available in the markets as a gum or tablets which you can
chew ,so it is a sugar free gum has the ability to remineralize
enamel subsurface lesions in human in situ models ,where the
addition of CPP-ACP to either sorbitol or xylitol –based sugar
free gum resulted in a CPP-ACP does-related increase in enamel
subsurface remineralization


They found after studies by Walsh that CPP-ACP will enhance
the effect of fluoride when combined together ,so a new product of
tooth mousse was used since the last year (CPP+F incorporated
together)

“chewing a sugar free gum containing Recaldent immediately after

brushing with fluoride toothpaste ,or proffessional gel application will
enhance the remineralization activity of the fluoride “Dr said .

BUT how CPP will enhance the effect of fluoride?

CPP keeps Ca ,P, and F in the solution(ionic) form theraby enhancing
the efficacy of the fluoride as a remineralizing agent


F won't remineralize teeth under low pH, as there isn’t available
Ca & P; CPP-ACP overcomes the pH barrier preventing F from
working

Student question which I couldn’t hear !but it was about if tooth

mousses with fluoride will increase flurosis?
Dr answered NO!coz fluoride is a developmental defect ,and it doesn’t
increase by any thing .

Uses of tooth mousse:

 
Caries prevention : protect teeth from effects of demineralization
even under extreme challenges from strong acids ,reverses early
white spot lesions .

It may be used for remineralization of hypoplastic molars also for
enamel hypoplasia and amelogenesis imperfecta it is very
effective.

Remineralizing erosion areas .

Remineralize white spot lesions(incipient caries that start as
chalky white lesions after orthodontic tt or ortho. Brackets .

Dentin hypersensitivity.

Incorporated into GIC restorative materials .

 Patients with a known allergy to cow’s milk should avoid this

product
There is no age constrictions on CPP use

Instructions:
When you prescribe tooth mousse for your patient you should :
 Explain the product :
 Tooth mousse is commercially available only through
dentists (not available in the pharmacies)
 Active ingredients of CPP-ACP is derived from cow’s
milk ,so if there is any allergies to milk the child shouldn’t
use it

It is OK to use with lactose intolerance (there is no lactose
in tooth mousse )
 Extensively tested ,very safe ,minimal side effects if any .
(some patients may feel nausea but this nausea is also felt in
these people after drinking milk ,so it is not considered an
allergy )
 Highly effective in remineralizing enamel
 It works well with fluoride
The regimen that the the Dr use usually with her patients ,she get them
to brush their teeth ,prescribe fluoride mouth rinse for them ,and give
them tooth mousse to use before sleep

 Explain benefits of tooth mousses (uses)


Explain how should it be used :

Rub on tooth surfaces after brushing.
Apply it by fingers like any cream or the child can place it
on his tooth brush and simply brush his teeth and by a
floss the child can get it interdentaly ,in the clinic you can
place it in fluoride gel tray and apply for 5 minutes

Recommend the use twice daily
after morning brushing and befor going to bed .
 Obtain consent from parents for use.

Explain need to evaluate product to determine effects
on your patient for long time use.(patients may don’t
like the product‘s taste or may feel nausea so it is
good to ask your patient about the product)
 Explain need to contact us if there are any problems.
Evaluate product use/patient at 1, 3, 6, 12 months. File in
case notes in patient's chart.

The last topic that we will talk about is the immunization:

 It is only under research

The only Ig reaching the mouth in appreciable amounts is
IgA in saliva. IgG & IgM are present in the exudates
from the gingival crevice in small amounts (as they come
from the plasma).
 Problems facing vaccination against caries are:
 Safety, it's not worthwhile to produce a vaccine against S.
mutans that produces side effects worse than caries. So since
caries is not a dangerous disease vaccination shouldn’t cause
side effects ,which are more dangerous than the disease itself .
 effictivness there is no vaccine 100%effective

 specifity ,vaccines are highly specific .

 acceptability of the parents (fears and cost),there is increased

public antipathy towards vaccination .

Recommendations:
Plus wearing gloves ,masks,and glasses when you touch the
patient ,doing FS or what ever you do to ur patient you should:

Prescribe CHX when indicated 2 caries (use gel for
those who can't rinse).

Prescribe F m/rinses (daily .05%) & F gel, encourage TB
twice/day.
 Encourage pregnant mothers & caregivers, & children 2
chew sugar-free gum

Use of CPP (tooth mousse, Recaldent gum.
Finaly ,what the Dr wants us to know after this lecture that
we can use all of these agents ,the more we use the better
(within accepted limits)and when you combine them
together you get the most effect

done by your sister :Heba .A .Ali

The end