PRESENTED BY G.

SRINIVAS 2ND YEAR PG DEPT OF PERIODONTICS DATE: 19/8/11

Contents
Introduction Definition The concept of chemical supragingival plaque control Chemical supragingival plaque control Rationale for chemical supragingival plaque control Approaches to chemical supragingival plaque control

-Antiadhesive agents -Antimicrobial agents -Plaque removal agents -Antipathogenic agents

Contents
Vehicles for the delivery of chemical agents
Chemical plaque control agents Chlorhexidine mouth wash

-toxicology and side effects -chlorhexidine staining -mechanism of action -chlorhexidine products -clinical use of chlorhexidine References

Introduction
Epidemiological studies revealed a peculiarly high

correlation between supragingival plaque levels and chronic gingivitis ---Ash et al. 1964

Clinical research(Loe et al. 1965) led to the proof that

plaque was the primary etiological factor in gingival inflammation.

Definition
Plaque control is the removal of dental plaque on a

regular basis and the prevention of its accumulation on the teeth and adjacent gingival surfaces.

THE CONCEPT OF CHEMICAL SUPRAGINGIVAL PLAQUE CONTROL

The use of chemical agents should be as adjuncts & are not

replacements for mechanical methods.

These appear partially or totally ineffective alone.

Many individuals remove only around half of the plaque

from their teeth even when brushing for 2 minutes (de la Rosa 1979).
The adjunctive use of chemicals would overcome the

deficiencies in mechanical tooth cleaning habits.

Chemical supragingival plaque control

History of oral hygiene products:
The terminology "oral hygiene products" is recent but

there is evidence dating back at least 6000 years that formulations and recipes existed to benefit oral and dental health (Fischman 1992, 1997).
A considerable number of formulations can be

attributed to the Hippocrates (circa 480 BC).

 Alcohol-based mouthrinses were particularly popular

with the Romans and included white wine and beer.

Urine, as a mouthrinse, appeared to be popular with

many peoples and over many centuries.

Cantabri and other peoples of Spain preferred stale

urine
whereas Fauchard (1690-1761) in France

recommended fresh urine.

Rationale for chemical supragingival plaque control

Etiology of both gingivitis and periodontitis is dental

plaque and plaque bacteria.

This supports the concept of employing chemical

agents to control plaque.

This is the concept that underlies chemical

supragingival plaque control.

Approaches to chemical supragingival plaque control

Chemical agents, on the other hand, could influence

plaque quantitatively and qualitatively via a number of processes . The action of the chemicals could fit into four categories: 1. Antiadhesive 2. Antimicrobial 3. Plaque removal 4. Antipathogenic

Antiadhesive agents
These would act at the pellicle surface to prevent the initial

attachment of the primary plaque forming bacteria.

Acting most effectively on an initially clean tooth surface.

 Prevent the attachment and development of biofilms. Described as antifouling agents.

Antiadhesion and plaque removal, has been shown

effective against plaque and gingivitis (Collaert et al. 1992, Claydon et al. 1996).
Amine alcohol & Delmopinol interferes with the

bacterial matrix formation.

Antimicrobial agents
Antimicrobial agents could inhibit plaque formation

through one of two mechanisms alone or combined. 1. inhibition of bacterial proliferation (bacteriostatic effect). 2. Bacteriocidal effect whereby the antimicrobial agent destroys all of the microorganisms either attaching or already attached to the tooth surface.

Plaque removal agents

Chemical plaque removal agents has attracted the

terminology of "the chemical toothbrush".

There are potential agents, such as the hypochlorites,

which might be expected to remove bacterial deposits.

The nearest success was with enzymes directed at both

the pellicle( e.g. proteases) or the bacterial matrices, e.g. dextranase and mutanase (Kornman 1986).

Antipathogenic agents
Inhibit the expression of the pathogenicity without

necessarily destroying the microorganisms.

In some respects antimicrobial agents, which exert a

bacteriostatic effect, achieve such results.

Vehicles for the delivery of chemical agents

The carriage of chemical agents into the mouth for

supragingival plaque control has involved a small but varied range of vehicles ( Addy 1994, Cummins 1997).

Tooth pastes
Ideal vehicle for the carriage of plaque

control agents is toothpaste.

The major ingredients may be

classified under the following headings: 1.Abrasives 6. Flavors 2.Detergents 7. Actives 3.Thickeners 4.Sweeteners 5. Humectants

 The addition of cationic antiseptics to toothpastes is

difficult but chlorhexidine has been formulated into toothpastes and shown to be effective ( Yates et al. 1993, Sanz et al. 1994).

Mouthrinses
Mouthrinses are less complex

than toothpastes.
Anionic detergents are included

in some products but, again, cannot be formulated with cationic antiseptics such as cetylpyridinium chloride or chlorhexidine (Barkvoll et al. 1989).

 Ethyl alcohol is commonly used both to stabilize

certain active ingredients and to improve the shelf-life of the product.

The proportion of alcohol is usually less than 10% but

some rinses have in excess of 20% alcohol.

Spray
Spray delivery of chemical plaque control agents has

attracted both researchers and manufacturers.

Sprays have the advantage of focusing delivery on the

required site.
The dose is clearly reduced and for antiseptics such as

chlorhexidine this has taste advantages.

 When correctly applied chlorhexidine sprays were as

effective as mouthrinses for plaque inhibition although there was no reduction in staining (Francis et al. 1987a, Kalaga et al. 1989a).

Chlorhexidine sprays were found particularly useful for

plaque control in physically and mentally handicapped groups (Francis et al. 1987a,b, Kalaga et al. 1989b).

Irrigators
Irrigators were designed to spray

water, under pressure, around the teeth.

They only remove debris, with

little effect on plaque deposits ( Frandsen 1986).

Chewing gum
Significant benefits to dental

health through the use of sugarfree chewing gum.

Unfortunately, chewing gums

alone have little plaque control benefits particularly at sites prone to gingivitis ( Addy et al. 1982a).

Varnishes
Though Varnishes have been

employed to deliver antiseptics including chlorhexidine, but the purpose has been to prevent root caries rather than as a reservoir for plaque control.

CHEMICAL PLAQUE CONTROL AGENTS

The number and variation of chemical agents

evaluated are quite large,

Most have antiseptic or antimicrobial actions and

success has been variable at the extreme.

 The most effective agents inhibit the development of

plaque and gingivitis

Limited to affect established plaque and gingivitis. Chemical plaque control agents have been the subject

of many detailed reviews since 1980 (Hull 1980, Addy 1986, Kornman 1986)

 Persistence of action, sometimes termed

substantivity (Kornman 1986), appears to dependent on several factors:

1. Adsorption and prolonged retention on oral surfaces

including, importantly, pellicle coated teeth.

2. Maintenance of antimicrobial activity once adsorbed

primarily through a bacteriostatic action against the primary plaque forming bacteria.
3. Minimal or slow neutralization of antimicrobial

activity within the oral environment or slow desorption from surfaces.

1. Bisbiguanide antiseptics 2. Quaternary Ammonium Compounds 3. Phenolic Antiseptics 4. Hexetidine 5. Povidone Iodine 6. Triclosan 7. Delmopinol 8. Salifluor 9. Metal Ions 10. Natural Products 11. Oxygenating Agents

1. Bisbiguanides (Addy et al1994)

Kills a wide range of

microorganisms by damaging cell wall.

Bisbiguanide antiseptics

that possess antiplaque activity are: Chlorhexidine Alexidine Octenidine

2. Quaternary Ammonium Compounds (Mandel 1988)

Have moderate plaque inhibitory activity Greater oral retention and equivalent

antibacterial activity to chx

Less effective in inhibiting plaque and

preventing gingivitis

 Example of QAC are Benzalconium chloride

cetylpyridinium chloride (CPC)

Most effective in 0.05% formulations

Available as CPC rinses and CPC

lozenges (Cepacol)
Causes staining

3. Phenolic Antiseptics (Mandel 1988)

Used either alone or in combination with mouth rinses

or lozenges
Has moderate plaque inhibiting effects and some anti-

inflammatory effects in reducing gingivitis

E.g. is Listerine, which is an essential oil/phenolic

mouthwash

 Its lack of profound plaque inhibitory effect is because

of poor oral retention

Thus, Listerine has moderate effect on plaque re-

growth and some anti inflammatory effect which may reduce the severity of gingivitis

4. Hexetidine
Has some plaque inhibitory activity
Oral retention: 1 3 hours, which

accounts for the low plaque inhibitory effects Concentrations > 0.1% can cause oral ulceration Combining zinc with hexetidine improves its plaque inhibiting activity Product: Oraldene

5. Povidone Iodine
No significant activity when used

as 1% mouthwash

Can cause iodine sensitivity

Either full strength or equal parts

of povidone iodine and water is used for subgingival irrigation.

6. Triclosan
Non-ionic antiseptic

Has moderate plaque inhibitory effects

Usually used in combination with zinc to increase oral

retention

 Acts as an anti-inflammatory agent in mouth rinses

and toothpastes Inhibits cyclo-oygenease and lipooxygenase thus reducing prostaglandins and leukotrienes

Anti-inflammatory effect depends on its ability to

penetrate into gingival tissues.

 Brushing with a Triclosan

toothpaste reduces gingival inflammation

Effective formulations:

Triclosan/ Copolymer Triclosan/ Zinc Citrate

7. Delmopinol
Has plaque inhibiting effects:

Interferes with plaque matrix formation and reduction of bacterial adherence

Formulations: 0.1% and 0.2%

Possesses anti-inflammatory effects

 Reductions in dextran-producing

streptococci

Side effects:

Transient numbness of tongue Tooth and tongue staining Taste disturbances Mucosal soreness Erosion

8. Salifluor
Is a salicylanide which has anti-bacterial and

inflammatory properties
Mechanism of action is not fully understood Experimentally 0.12% is as effective as 0.12%

chlorhexidine.

9. Metal Ions
Zinc, copper, and tin possess

(Addy et al. 1994)

plaque inhibitory effect

Copper and tin causes staining Fluoride compounds such as

stannous fluoride and amine fluoride have plaque inhibitory effect .

 Zinc is retained by dental plaque and inhibits its

regrowth without disrupting oral ecology

Zinc has additive or synergistic effect with hexetidine,

Triclosan and sanguinarine

10. Natural Products (Mandel 1988)

1. Sanguinarine 2. Propolis

Sanguinarine:
Is retained in plaque for several hours after use and is

poorly absorbed by GIT

Mode of action: inhibition of glycolysis with assistance

from zinc

 Is an effective plaque inhibitory

agent but less effective than chlorhexidine

Prevents development of gingivitis

Mouthwash is more effective plaque

inhibitory agent than toothpaste.

Propolis:
Has an antiseptic, anti-

inflammatory, antimycotic and bacteriostatic effect

Not effective as mouthwash

11.Oxygenating Agents(Addy et al. 1994)

Examples:

Hydrogen peroxide Buffered sodium peroxyborate Peroxycarbonate

Inhibits anaerobic bacteria

As obligate anaerobes are important in

the development of gingivitis and periodontitis, these effects are useful

Alcohol Content of Mouthwashes

Many mouthwashes contain significant quantities of alcohol,

which leads to a number of possible disadvantages:

If accidentally swallowed by young children it can cause alcohol toxicity Can increase the incidence of oral and pharyngeal cancer Reduces hardness of composite and hybrid-resin restorations

CHLORHEXIDINE
Chlorhexidine is

available in three forms,

1.digluconate, 2.acetate and 3.hydrochloride salts.

 Most studies and most oral formulations and products

have used the digluconate salt, which is manufactured as a 20% V/V concentrate.

Digluconate and acetate salts are water-soluble but

hydrochloride is very sparingly soluble in water.

 Chlorhexidine was developed in the 1940s by Imperial

Chemical Industries, England, and marketed in 1954 as an antiseptic for skin wounds.
Later, the antiseptic was more widely used in medicine

and surgery.
Use in dentistry was initially for presurgical

disinfection of the mouth and in endodontics.

 Plaque inhibition by chlorhexidine was first

investigated in 1969 (Schroeder 1969).

The definitive study was performed by Loe and

Schiott (1970).

This study showed that rinsing for 60 seconds twice

per day with 10 ml of a 0.2% (20 mg dose) chlorhexidine gluconate solution in the absence of normal tooth cleaning, inhibited plaque regrowth and the development of gingivitis.

 Chlorhexidine is a bisbiguanide antiseptic, Being a symmetrical molecule consisting of four

chlorophenyl rings,
Two biguanide groups connected by a central

hexamethylene bridge.

 The compound is a strong base and dicationic at pH

levels above 3.5, with two positive charges on either side of a hexamethylene bridge (Albert & Sargeant 1962).

Indeed, it is the dicationic nature of chlorhexidine,

making it extremely interactive with anions, which is relevant to its efficacy, safety, local side effects and difficulties with formulation in products.

Safety, toxicology and side effects

The cationic nature of chlorhexidine minimizes

absorption through the skin and mucosa, including from the GI tract.
Systemic toxicity from topical application or ingestion

is therefore not reported,

There is no evidence of teratogenicity in the animal

model.

 Neurosensory deafness can occur if chlorhexidine is

introduced into the middle ear.

In oral use as a mouthrinse, chlorhexidine has been

reported to have a number of local side effects (Flotra et al. 1971).

Chlorhexidine staining
The mechanisms proposed for chlorhexidine staining

can be debated (Eriksen et al. 1985, Addy & Moran 1995, Watts & Addy 2001) but have been proposed as:

1. Degradation of the chlorhexidine molecule to release parachloraniline 2. Catalysis of Maillard reactions 3. Protein denaturation with metal sulfide formation 4. Precipitation of anionic dietary chromogens.

 Oral mucosal erosion

appears to be an idiosyncratic reaction and concentration dependent. Dilution of the 0.2% formulation to 0.1%, but rinsing with the whole volume to maintain dose, usually alleviates the problem. Erosions are rarely seen with 0.12% rinse products used at 15 ml volume.

 Unilateral or bilateral

parotid swelling
This is an extremely rare

occurrence and an explanation is not available

 Taste perturbation where the salt taste appears to be

preferentially affected (Lang et al. 1988) to leave food and drinks with a rather bland taste.

Chlorhexidine also has a bitter taste, which is difficult

to mask completely

Enhanced supragingival calculus formation.

 This effect may be due to the precipitation of salivary

proteins on to the tooth surface, thereby increasing pellicle thickness and/or precipitation of inorganic salts on to the pellicle layer.

Certainly pellicle forming under the influence of

chlorhexidine shows an early and highly calcified structure (Leach 1977).

Mechanism of action
Chlorhexidine is a potent antibacterial substance but

this alone does not explain its antiplaque action.

The antiseptic binds strongly to bacterial cell

membranes.
At low concentration this results in increased

permeability with leakage of intracellular components including potassium (Hugo & Longworth 1964, 1965).

 At high concentration, chlorhexidine causes

precipitation of bacterial cytoplasm and cell death (Hugo & Longworth 1966).

In the mouth chlorhexidine readily adsorbs to surfaces

including pellicle-coated teeth.

Once adsorbed chlorhexidine shows a persistent

bacteriostatic action lasting in excess of 12 hours (Schiott et al. 1970).

 A more recent study and review suggested that plaque

inhibition is derived only from the chlorhexidine adsorbed to the tooth surface (Jenkins et al. 1988).

It is possible that the molecule attaches to pellicle by

one cation leaving the other free to interact with bacteria attempting to colonize the tooth surface.

It would also explain why anionic substances such as

sodium lauryl sulfate based toothpastes reduce the plaque inhibition of chlorhexidine if used shortly after rinses with the antiseptic (Barkvoll et al. 1989).

 A more recent study has demonstrated that plaque

inhibition by chlorhexidine mouthrinses is reduced if toothpaste is used immediately before or immediately after the rinse (Owens et al. 1997).

Plaque inhibition by chlorhexidine mouthrinses

appears to be dose related (Cancro et al. 1973, 1974, Jenkins et al. 1994).

Chlorhexidine products
Mouthrinses:

0.2% 0.1% 0.12%

Gel:

1% chlorhexidine gel 0.2%, 0.12% are also available

 Sprays:

0.1% and 0.2% chlorhexidine sprays

Varnishes: Toothpaste:

More recently, a 1% chlorhexidine toothpaste with and without fluoride was found to be superior to the control product for the prevention of plaque and gingivitis in a 6-month home use study (Yates et al. 1993).

CLINICAL USES OF CHLORHEXIDINE

As an adjunct to oral hygiene and

professional prophylaxis
Postoral surgery including periodontal

surgery or root planing

For patients with jaw fixation For oral hygiene and gingival health

benefits in the mentally and physically handicapped

 Medically compromised individuals predisposed to

oral infections
High-risk caries patients
Recurrent oral ulceration, Subgingival irrigation Removal and fixed orthodontic appliance wearers

In denture stomatitis
Immediate preoperative chlorhexidine rinsing and

irrigation

conclusion
The concept of chemical plaque control may be

justified as a means of overcoming inadequacies of mechanical cleaning.

Chemical plaque control can augment mechanical

plaque control procedures.

The use of chemical agents should be as adjuncts and

not replacements for the more conventional and accepted effective mechanical methods.

References
Lindhe ; Clinical periodontology and implant

dentistry; 4th and 5th edition. Carranza; Clinical periodontology; 9th and 10th edition. Antimicrobial mouthrinses: overview and update; MandelD; J Am Dent Assoc. 1994 Aug;125 Suppl 2:2S10S. Cytotoxicity of Mouthrinses on Epithelial Cells by Micronucleus Test; Ebru Olgun Erdemira, DDS, PhD. In-vitro evidence for efficacy of antimicrobial mouthrinses; Pauline C. Pana,*; J Dent. 2010 June ; 38(Suppl 1):

 0.2% Chlorhexidine Mouthwash With an

Antidiscoloration System Versus 0.2% Chlorhexidine Mouthwash: A Prospective Clinical Comparative Study; Carols Sols,*; J Periodontol 2011;82: 80-85. Modern supragingival plaque control; Iacono VJ; Int Dent J. 1998 Jun;48(3 Suppl 1):290-7. New agents in the chemical control of plaque and gingivitis: reaction paper; O'Mullane D; J Dent Res.1992 Jul;71(7):1455-6. Clinical and microbiological benefits of strict supragingival plaque control as part of the active phase of periodontal therapy; Magda FERES; J Clin Periodontol. 2009 October ; 36(10): 857867.

 Chemical agents to prevent and regulate plaque

development; DANIELH . FINE; Periodontology 2000, Vol. 8, 1995, 87-107. Current patterns of oral hygiene product use and practices; BASHARB AKDASH; Periodontology 2000. Vol. 8, 1995, 11-1 4. O.O. AKANDE, A.R.A. ALADA; EFFICACY OF DIFFERENT BRANDS OF MOUTH RINSES ON ORAL BACTERIAL LOAD COUNT IN HEALTHY ADULTS; African Journal of Biomedical Research, Vol. 7 (2004); 125 128.