ANTI-PLAQUE & ANTICALCULUS AGENTS

PRESENTED BY: DR. AARTI CHOPRA

Plaque: Plaque is defined clinically as a structured, resilient, yellowish-grayish substance that adheres tenaciously to the intraoral hard surfaces, including removable and fixed restorations. Materia alba: refers to soft accumulations of bacteria and tissue cells that lack the organized structure of dental plaque and it is easily displaced with a water spray. Calculus: Calculus is a hard deposit that forms by mineralization of dental plaque and it is generally covered by a layer of unmineralized plaque.

PLAQUE CONTROL

Mechanical plaque control:

With the help of tooth brush, dentrifrices, interdental cleaning aids, gingival massage, oral irrigators.

Chemical plaque control:

With the help of antiplaque and anticalculus agents.

Chemical plaque control Rationale

Gingivitis & periodontitis are highly prevalent diseases and prevention of occurrence or re-ocurrence is dependent on supragingival plaque control. Mechanical tooth cleaning through toothbrushing with tooth paste is the most common method of oral hygiene practiced. Tooth cleaning is largely influenced by the compliance and dexterity of the individual. The concept of chemical plaque control can be justified as a means of overcoming inadequacies of mechanical cleaning.

Uses of antiplaque agents

To replace mechanical tooth brushing when this is not possible in situations like: - After oral or periodontal surgery during the healing
period. - After intermaxillary fixation used to treat jaw fractures. - With acute oral mucosal or gingival infections when pain & soreness prevents mechanical oral hygiene. - For mentally or physically handicapped patients who are unable to brush their teeth.

As an adjunct to normal mechanical oral hygiene in situations where this may be compromised by discomfort or inadequacies: - Following sub-gingival scaling & root planing when
gingivae may be sore for a few days. - Following scaling when there is hypersensitivity due to root exposure. - Following scaling when patients oral hygiene remains inadquate.

Classification of Antiplaque agents

1. On the basis of mechanism of action:

Antiadhesives Antimicrobial Plaque removal Antipathogenic

2. On the basis of chemical nature: Bisguanides: chlorhexidine, alexidine, octenidine Quarternary ammonium compounds: benzalkonium chloride, cetyl pyridinium chloride Phenols and essential oils: listerine Fluorides: sodium fluoride, stannous fluoride, organic amine fluoride Antiseptics: iodine, povidone iodine, chloramine To Antibiotics: penicillin, tetracycline, vancomycin, spiramycin, kanamycin, streptomycin, actinomycin, erythromycin, bacitracin etc. Oxygenating substances: hydrogen peroxide, buffered sodium peroxyborate

Enzymes: protease, amylase, mutanase, amyloglycosidase, glucose oxidase and amyloglucosidase Plant alkaloid: sanuinarine Metal ions: Zn, Cu, Sn Triclosan Other agents: salifluor, delmopinol, detergents, propolis, hexetidine.

3. On the basis of form: Mouthrinses Sprays Irrigators Chewing gums Varnishes

Bisguanides
Several bisguanides possess antiplaque activity, including chlorhexidine, alexidine, octenidine. However chlorhexidine is the most studied and used.

CHLORHEXIDINE

Chlorhexidine- the digluconate of chlorhexidine is a synthetic antimicrobial which was developed in late 1940s. Loe & Schiott introduced this agent as an oral antimicrobial agent (0.2%) and have shown that 5, 2 and even 1 daily rinse prevented plaque accumulation and development of gingivitis over 21 day period of no oral hygiene. Clinical studies of several month duration have reported plaque reductions of 45% to 61% and gingivitis reductions of 27% to 67%.

MECHANISM OF ACTION: Chlorhexidine is a base and is stable as a salt. The most common preparation is chlorhexidine digluconate that is water soluble and at physiologic pH readily dissociates releasing the positively charged chlorhexidine component. Access to the bacterial cell wall is enhanced by the electrostatic force between positevly charged chlorhexidine cations and negatively charged lipoteichoic acid and other components of bacterial cell wall, thereby altering the osmotic equilibrium. Having gained access to the inner cell membrane, chlorhexidine disorientates its lipoprotein structure causing destruction of the osmotic barrier and resulting in the leakage of intracellular components.

At low concentrations of chlorhexidine, small molecule weight substances such as potassium and phosphorus will leach out, exerting a bacteriostatic effect. At high concentrations of chlorhexidine, bactericidal effect occurs due to precipitation and coagulation of cytoplasm. Bactericidal effect is thought to be less important than the bacteriostatic effect, provided by the slow release of chlorhexidine. Chlorhexidine is more effective in preventing plaque accumulation on a clean tooth surface than in reducing pre-existing deposits.

1.

2.

3.

In addition to antibacterial properties, chlorhexidine also reduces bacterial colonization on tooth surface by 3 mechanisms: The effective blocking of acidic group of salivary glycoproteins will reduce their adsorption of hydroxyapatite and formation of acquired pellicle. The ability of bacteria to bind to the tooth surface may also be reduced by the adsorption of chlorhexidine to the extracellular polysaccharides of their capsules or glycocalyces. Chlorhexidine may compete with Calcium ions for acidic agglutination factors in plaque.

SPECTRUM OF ACTIVITY: Chlorhexidine has broad spectrum of activity and is effective against a wide variety of gram+ve and gram-ve organisms, yeasts and fungi. Gram+ve organisms are more sensitive than gram-ve organisms and streptococci are more sensitive than staphylococci. Rinsing with 10ml of 0.2% chlorhexidine for 1 min. has resulted in suppression of new plaque deposits.salivary bacterial counts taken immediately after rinsing with 0.2% solution demonstrated a 80% to 90% reduction of organisms. Subsequent to cessation of drug application salivary count of organisms return to baseline value within 48hrs. M

SUBSTANTIVITY OF CHLORHEXIDINE: The ability of the drug to absorb onto or bind to the soft and hard tissues is known as substantivity. Substantivity of chlorhexidine was first described in 1970s. What gives chlorhexidine its advantage over many other agents is its ability to bind strongly to many sites in the oral cavity. It is this substantivity that enables it to function as a form of slow release device and maintain an ongoing rather than intermittent antibacterial action. The proportion of chlorhexidine retained is directly dependent upon concentration, volume and pH in the mouth.

CLINICAL USAGE: It is accepted by FDA and ADA. Available as mouthwash- 0.2% chlorhexidine, recommended as 10ml per rinse and 0.12% chlorhexidine recommended as 15ml per rinse. Avialable as gel 1% It is more difficult to incorporate chlorhexidine into toothpastes because of binding of chlorhexidine to components in the toothpaste.

SAFETY OF CHLORHEXIDINE: Animal experiments have shown that primary route of ecretion is through faeces. It is poorly absorbed by the GIT and therefore displays very low toxicity. No evidence of carcinogenic or teratogenic alterations has been found. SIDE EFFECTS: Tooth staining High calculus scores Burning sensation Impairment in taste sensation

Quaternary ammonium compounds

Quaternary ammonium compounds such as cetylpyridinium chloride have moderate plaque inhibitory activity. Although they have greater initial oral retention and equivalent antibacterial action to chlorhexidine but they are less effective than chlorhexidine in inhibiting plaque and gingivitis. One reason for this may be that they are readily desorbed from the oral mucosa.

Phenols and essential oils

Phenols, either alone or in combination, have been used as mouthrinses or lozenges. Most phenols exert a non-specific action which is dependent upon the ability of drug. In its non-ionized form, it penetrates through the lipid component of the cell walls of gram-ve organisms and denatures the bacterial proteins. Listerine is an essential oil/phenolic mouthwash which has been shown to have moderate plaque inhibitory effects and some antigingivitis effects. It has been accepted by ADA to be an aid to home oral hygiene procedures.

Goodson et al (1985) demonstrated that after 9 month application of listerine, there was a reduction of nearly 80% in plaque toxic activity. Phenolic compounds are also known as scavangers of oxygen free radicals and hence should have an effect on leucocyte activity. Adverse effects are minimal and safety has been established by quite long clinical use. Some patients find an initial burning sensation and bitter taste. Occasional staining of minimal amount has been found.

Triclosan

Triclosan, a trichlora-2-hydroxydiphenyl ether, is a nonionic antiseptic which lacks the staining effects of cationic agents. It has been used recently in a number of commercial mouthwashes and toothpastes. It ha a broad antibacterial properties and moderate antiplaque properties when used in combination wit zinc. It has been found to retain in mouth and to have clinical efficacy without side effects.

The primary site of action is bacterial cellular membrane of bacteria. At bacteriostatic conc., triclosan prevents the uptake of essential amino acids. At bactericidal conc., it causes disorganization of the cellular membrane and leakage of cellular contents. Triclosan itself has little or no substantivity, its substantivity can be increased by its combination with copolymers of methoxyethylene and maleic acid ( Gantrex, ISP corps ). Despite its more rapid clearance, triclosan has been shown to be present in an elevated level in plaque and saliva for 8 hrs. and in the oral mucosa for 3 hrs. after tooth brushing. There is evidence that triclosan may also act as an antiinflammatory agent in mouthrinses and toothpastes. Antigingivitis effect of triclosan is due to its antiinflammatory property.

Plant / Benzophenathridine alkaloid

BPA was believed to be the active ingredient in tooth cleaning sticks used by the native cultures in africa. The active ingredient is Sanguinarine. Sanguinarine has been isolated from the alcoholic extract of powdered rhizomes of the blood root plant, Sanguinaria

candensis.

Sanguinarine contains the reactive iminium ions, these ions are retained in the plaque for several hours after use. Sanguinarine has cationic nature and acts by inhibiting thiol dependent enzymes. Acts partly by interferring with the membrane bound metallic constituents, reducing glycolysis and inhibiting the adherence of oral bacteria.

Sanguinarine appears to an effective plaque inhibitory agent but is less effective than chlorhexidine in this regard. Also unlike chlorhexidine it is not able to prevent the development of gingivitis. Mouthwash is much more effective than toothpaste. This may be due to binding of other components in the toothpaste to the chemically reactive site of sanguinarine. Commercial available mouthrinse contains sanguinarine in Zn ions- Viadent (0.03% Sanguinarine Zn chloride).

Enzyme preparations

The rationale of using enzymes as active agents in antiplaque preparations was that they would be able to break the matrix of already formed plaque and calculus. Furthermore, it was accepted that certain proteolytic enzymes would be bactericidal to plaque microorganisms. However, clinical trials on animals and humans have been disappointing. The initial efforts during 1950-1970 were to employ enzymes directly to degrade the intercellular matrix and plaque integrity. The following preparations were tested:

Preparation of dehydrated pancreas (Viokase) Mucinase Protease-amylase Fungal enzymes Dextranase Mutanase
All these preparations are of historic interest and they are not in use now.

Oxygenating agents

H2O2, sodium peroxyborate, peroxycarbonate are useful in ANUG . Futher investigations are required for these substances to act as antiplaque agent.

Antibiotics

Penicillins, Vancomycin, Niddamycin and Kanamycin have been used for antiplaque activity. All of these reduce significant amount of plaque formation. Potential problem with their use is of bacterial resistance. Hypersensitivity reaction on topical application are common. The potential benefit of using long term antibiotics is less than harm.

Metallic salts

Mainly Zn, Sn, Cu salts are having antiplaque and anticalculus activities. At high concentration they can be bactericidal. At sublethal levels: a. can inhibit plaque growth by altering the surface potential of plaque bacteria thus reducing the rate of bacterial deposition onto the teeth. b. can inhibit a number of enzyme systems relating to carbohydrate metabolism. c. can cause proteolysis. Zn citrate ( 0.5%, 1% ) has been utilized for years as antiplaque and anticalculus agent. In the laboratory, it can inhibit acid production by oral streptococci and trypsin like protease of P.gingivalis.

Anticalculus agents

Acids Alkalies Chelating agents Enzymes Urea Antimicrobials Metals Bisphosphonates Victamine C Pyrophosphates Polymers & copolymers

Acids
One of the earliest techniques to dissolve calculus was to use wooden stick moistened with Aromatic sulphuric acid (Barker 1872). This technique was modified by Niles (1881) who suggested the use of Nitomuriatic acid. Other acids included are: 20% trichloroacetic acid Bifluoride of mercury 10% sulphuric acid The problem with acids is that they are caustic to soft tissues and decalcify tooth structure. Stones (1939) reported that ability of an acid to dissolve tooth structure was greater than its ability to dissolve calculus.

Alkalies

Badanes (1929) noted the beneficial effect of Natural mineral waters on the removal of calculus because of its alkalie content. It dissolves the three principle constituents of salivary calculus; globulin, mucin and calcium oxalate. But this idea did not find support.

Chelating agents

Chelating agents are used to dissolve crystallized calcium salts and are capable of combining with calcium to form stable compounds. Sodium hexametaphosphate was found to remove supragingival calculus from extracted teeth in 10-15 days (Kerr & Field 1944). Warren et al (1964) found that with sodium hexametaphosphate decalcification of cementum was greater than that of calculus. Because of this finding its use was ceased. EDTA gel ( Sofscale) has been used as a prescale gel to soften the caculus by Jabro etal in 1992. but its efficacy has not been supported by other studies.

Enzymes

The mode of action of enzyme preparation is to break down plaque matrix or to affect the binding of calculus to the tooth. The first enzyme to be tested was mucinase (Stewart 1952) and it was found to reduce caculus formation and calculus which did form was softer and more easily removed. Dehydrated pancreas ( Viokase ) was found to rduce calculus formation by 60% (Jensen et al 1959). Viokase was introduced into chewing gums. Enzymes of fungal origin have been found to be superior to Viokase in reducing calculus formation (40.5% v 14.5%).

Urea

The idea of using urea as a anticalculus agent stems from its solvent action on protein. Urea at a concentration of 30% causes maximum reduction of calculus. Acetohydroxamic acid ( AHA ) irreversible inhibitor of urease has been studied as an anticalculus agent but results are not significant and further it leads to increase in caries.

Antimicrobials

Penicillin, Cetylpyridinium chloride, Niddamycin, Triclosan and chlorhexidine have been studied as an anticalculus agent. Out of these penicillin and cetylpyridinium chloride have not been found to decrease calculus levels. Although chlorhexidine is a potent antiplaque agent but it leads to increase in calculus levels ( Loe etal 1976, Lang et al 1982, Grossman et al 1986 ). Niddamycin (CC10232) has been found to decrease calculus formation but it is not used because of concern for bacterial resistance. Triclosan has been found to asist in plaque control and inhibition of calculus formation although to what extent, its not clear. It is predominantly used in combination with other anti-calculus agents.

Metals

Metal salts inhibit calculus formation by two mechanisms. Firstly they inhibit plaque formation by causing metabolic changes in bacterias. Secondly they inhibit mineralization. A dentrifrice containing zinc chloride and sodium floride has been shown to retard calculus formation.

Bisphosphonates
Bisphosphonates are a group of synthetic pyrophosphate analogue which prevent calculus deposition by inhibiting crystal growth. The bisphosphonates studied for their anticalculus effect are as follows and all of them have been found to reduce caculus formation.

EHDP (Ethanehydroxydiphosphonate) Sodium etidronate DPD (Diphosphono-propane-dicarboxylic acid) AHP ( Azacycloheptane 2,2-diphosphonic acid ) PBTA ( 2-phosphonobutane 1,2,4 tricarboxylate )

Victamine C

It is a surface active organophosphorous compound that has been found to be effective in inhibiting the invitro crystallization of calcium phosphate onto the smears of supragingival calculus. Victamine C has a specific taste that leads to increased salive flow that leads to reduction in calculus.

Pyrophosphates

Prevent calcification by interrupting the conversion of amorphous cacium phosphate to hydroxyapatite. The results from clinical studies are not found to be significant so they are not in use.

Polymers and copolymers

The following agents have been tried: Oligomer of sufoacrylic acid EDITEMPA BTC/copolymer mixture Gantrez (0.05% solution of methoxyethylene and maleic acid) All of them have been shown to have anticalculus effect either alone or in combination with other agents such as combination of incorporation of copolymer in a periodontal pyrophosphate/NaF paste.