Chemical plaque control

The role of dental plaque in the initiation of periodontal inflammatory diseases has been well established 1 Elimination of plaque and preventing its formation is the cornerstone of periodontal therapy. The chemical plaque control as an adjunct to mechanical plaque control has been used effectively to eliminate dental plaque. In an experimental study, it has been shown that a complete inhibition of plaque and prevention of gingivitis could be achieved by daily application of 0.2%  (CHX) 2. Many other studies have supported the significant plaque reduction with the use of chemical plaque control measures 3-6. However, it must be remembered that the chemical plaque control is an adjunct to mechanical plaque control and cannot eliminate plaque when used as monotherapy. Further, presently there are insufficient data, authenticating their long-term usage.

In the previous chapter, we discussed various methods of mechanical plaque control. In this chapter, we shall discuss in detail various chemicals (organic and inorganic) which are used to control plaque formation by inhibiting the accumulation, growth, and survival of microbiota involved in plaque formation.

History of chemical plaque control

Probably the first chemicals used for plaque removal were dentifrices which have been used in conjunction with mechanical aids for centuries. Egyptians used tooth powders or pastes to clean their teeth, as did the ancient Greeks and Romans. Egyptians used to chew sodium carbonate to freshen their breath. They also used to rinse their mouth with honey and water to which goose fat, frankincense, cumin, and ocher had been added. The Romans used to rinse their mouth with Portuguese urine. It was believed that ammonia in urine aided in the disinfection of mouth and could whiten teeth. This practice was so popular that Nero had to place a tax on it. The practice remained popular until the 18th century. The Chinese medicine has been credited with the first reference (around 2700 BC) to use child urine as a mouth rinse to treat gum diseases 7. During the 12th century, Saint Hildegard von Bingen, a German philosopher advised mouth rinses with pure, cold water to prevent plaque and tartar formation. In the 16th century during the medieval period, people used mint and vinegar rinsing solutions to clean their mouth and get rid of bad breath. The chemical plaque control agents which are popularly known today as mouthwashes began their journey in the late 1800s. Alcohol was used as the primary agent in these preparations to reduce bacterial load in the oral cavity. Presently, most of the mouth rinses contain anti-microbial substances which not only inhibit the bacterial plaque formation, but also stay in the oral cavity for a long duration of time for their continued activity.

Classification of chemical plaque control agents

The European Federation of Periodontology in European workshop on Periodontology in 1996 8, used four terminologies to describe various agents used for chemical plaque control,

Antimicrobial agents: According to the consensus report, these are those chemicals that have a bacteriostatic or bactericidal effect in vitro that alone cannot be extrapolated to a proven efficacy against plaque in vivo.

Plaque reducing/inhibitory agents: These are the chemicals that have only been shown to reduce the quantity and/or affect the quality of plaque, which may or may not be sufficient to influence gingivitis and/or caries.

Anti-plaque agents: These chemical agents have an effect on plaque sufficient to benefit gingivitis and/or caries.

Anti-gingivitis agents: These are the chemicals which reduce gingival inflammation without necessarily influencing bacterial plaque (includes anti-inflammatory agents).

Another classification 7, 9 describes 3 generations of chemical plaque control agents (Table 46.1). In this classification, agents in the first and second generation have been classified according to their substantivity 10.

1st generation:  These are antibacterial agents with limited substantivity in vivo. They are capable of reducing plaque scores by 20-50%. The examples include antibiotics, phenols, quaternary ammonium compounds, metallic ions, sanguinarine etc.

2nd generation:   These are antibacterial agents with high substantivity. They are 70-90% more effectively retained by oral tissues than first generation agents and are slowly released. An example includes Bisbiguanides.

3rd generation: These agents are relatively new preparation which inhibits plaque growth and gingivitis by interfering with the plaque matrix formation and also by reducing bacterial adhesion and adherence. An example includes Delmopinol.

Table 46.1 Chemical plaque control agents

Generation
Compounds
Primary components
First generation agentsPhenols and essential oilsThymol
Hexylresorcinol
Eucalyptol
Triclosan
Metal saltsTin
Zinc
Copper
Stannous fluoride
Natural productsSanguinarine
Propolis
FluoridesSodium fluoride
Sodium monofluoro-phosphate
Stannous fluoride
Amine fluoride
Antibiotics and Antimicrobial agentsPenicillin
Vancomycin
Kanamycin
Niddamycin
Spiramycin
Quaternary ammonium compoundsEtylpyridinium chloride
Benzalconium chloride
Oxygenating agentsHydrogen peroxide
Sodium peroxyborate
Sodium peroxycarbonate
EnzymesProtease
Lipase
Nuclease
Dextranase
Mutanase
Surfactants/DetergentsSodium lauryl sulfate
Second generation agents BisbiguanidesChlorhexidine
Alexidine
Octenidine
Third generation agentsAmine alcoholsOctapinol
Delmopinol

The chemical agents used for plaque control can act at various stages of plaque formation. The agents which interfere with the initial bacterial adhesion to the tooth surface can be considered as anti-adhesive agents. These act on the dental pellicle and prevent initial adhesion of bacteria, thus may be considered as the most effective agents for the prevention of plaque formation. Unfortunately, we do not have any effective agent in this category which can be used safely for long-term without unwanted adverse effects. Some recently introduced agents such as amine alcohol and delmopinol have shown properties of inhibiting plaque matrix formation 11, 12.

The next step in plaque formation is plaque maturation which is characterized by the accumulation of Gram-positive and Gram-negative bacteria. These bacteria form a well-organized structure, known as plaque biofilm. At this stage agents who inhibit the plaque maturation are the anti-microbial agents. The anti-microbial agents can act on………………….

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

After the formation and maturation of plaque, chemical agents may be used as plaque removal agents. In other words, we can say that these agents may be used to remove plaque in a similar way as in the mechanical plaque control. Term “chemical toothbrush” has been used to describe these agents. In oral environment, the most closely suited plaque removal agents are enzymes such as proteases or bacterial matrices (dextranase and mutanase) 14. However, the practical applicability of these enzymes in oral environment has not been well established due lack of substantivity and local side effects.

Another approach to control the pathogenic plaque formation in the oral cavity is the probiotic approach. The word probiotic is derived from a Greek word meaning “for life”. Probiotic approach needs a detailed discussion but briefly, Lactobacilli have been shown to interact with various members of oral flora, thereby inhibiting the growth of periodontopathogenic microorganism 15. A study demonstrated significantly reduced gingival index and bacterial plaque amount in patients treated with Lactobacillus reuteri than in a placebo group. The authors concluded that this probiotic was effective in reducing gingivitis and bacterial plaque deposition in patients with moderate-to-severe gingivitis 16. Probiotics have also been shown to reduce the risk for a high Streptococcus mutans level occurrence, thereby reducing caries risk 17-19.

Another approach suggested by Lindhe 20 is the use of anti-pathogenic agents. These agents may reduce the pathogenicity of periodontal pathogens without necessarily destroying them. However, this approach is still hypothetical and requires more research.

Formulations containing chemical plaque control agents

Presently, there are various formulations carrying chemical plaque control agents, including dentifrices (toothpastes and tooth-powders), mouth rinses, sprays, oral irrigators, chewing gums and varnishes.

Dentifrices

Dentifrices are the integral part of daily oral health maintenance. They not only help in cleaning and polishing the teeth, but also the fresh feeling that comes with the use of a dentifrice while tooth brushing is liked by most people. These are available in paste, powder, gel or liquid form. Dentifrice is also the French word for toothpaste.

History of dentifrices:

The history of dentifrices may be tracked back to the time of the Egyptians, Greeks, and Romans. Egyptians are known to make a tooth powder which consisted of ashes of ox hooves, myrrh, powdered eggshells, and pumice. Greeks improved it by adding abrasives such as crushed bones and oyster shells. Romans added powdered charcoal, powdered bark and flavoring agents in it.

Although the prescriptions of toothpastes have been found in the Ebers Papyrus, an Egyptian medical reference book, but Hippocrates (460-377 b.c.) was the first to recommend the use of dentifrices. This dentifrice was made up of ashes from hares and mice, as it was believed that animals which had strong teeth may pass this attribute to humans in the form of ash. The Romans used dentifrice which was made up of the powder obtained from grinding horns and animal skulls mixed with goat’s fat. The Chinese used a mixture of salt, musk, and urine, which they believed cleaned the teeth as well as improved gingival health.

In 1873, toothpaste was mass-produced for the first time. The major initiating factor for the development of new age dentifrices was the ‘chemo-parasitic theory of tooth decay’ proposed by WD Miller in 1890. It created a boom in the toothpaste industry and since then toothpastes with a variety of compositions and properties have been introduced in the market.  The first collapsible tube containing toothpaste was made by Dr. Washington Sheffield in 1892. It was named ‘Dr. Sheffield’s Creme Dentifrice’. Soon after the importance of fluoride in tooth calcification was realized, it was added to the toothpaste. Fluoride was first added to a toothpaste in the 1890s, which contained calcium fluoride as the active ingredient. In the 1950s, fluoride toothpastes received the American Dental Association’s approval. Procter & Gamble in 1955 launched the first clinically proven fluoride containing toothpaste.

Toothpastes:

Toothpastes are the most commonly used agents for the maintenance of oral health. Ideal toothpaste must have the following properties 21, 22,

  • It should cause a slight abrasion,
  • It should produce froth,
  • It should have acceptable taste,
  • It should have a bleaching effect
  • It should prevent plaque, calculus and caries development

 Composition of a toothpaste:Toothpaste is a colloidal suspension of a mixture of ingredients that must be carefully balanced in order to provide an efficacious, safe, and consumer friendly product. The primary ingredients of toothpaste are,

  • Abrasives
  • Thickening / Binding agents
  • Humectants
  • Solvents
  • Surfactants
  • Sweeteners
  • Flavoring agents
  • Coloring agents
  • Preservatives
  • Therapeutic agents

Table 46.2 Composition of toothpastes

Toothpaste components
Percentage by weight
Abrasive20 - 50 %
Water20 - 40 %
Humectants20 - 35 %
Detergent1 - 3 %
Thickening agent1 - 2 %
Flavor0 - 2 %
Sweetener0 - 2 %
Therapeutic agent0 - 2 %
Color or preservative0.05 – 0.5 %

Table 46.3 Components of a toothpaste

Abrasives
Surfactants
Humectants
• Alumina
• Aluminium trihydrate
• Calcium carbonate
• Sodium bicarbonate
• Sodium metaphosphate
• Calcium pyrophosphate
• Pumice
• Silica
• Bentonite
• Dicalcium phosphate
• Hydroxyapatite
• Kaolin
• Methacrylate
• Perlite (a natural volcanic glass)
• Polyethylene
• Zeolites
• Sodium lauryl sulfate (SLS)
• Sodium N lauryl sarcosinate
• Sodium stearyl fumarate
• Sodium stearyl lactate
• Sodium lauryl sulfoacetate
• Amine fluorides
• Dioctyl sodium sulfosuccinate
• Water
• Glycerol
• Pentatol PPG (polypropylene glycol ethers)
• Sorbitol
• Xylitol
• PEG 8 (polyoxyethylene glycol esters)
Thickening / Binding agentsFlavorsPreservatives
• Carbopols
• Sodium alginate
• Sodium aluminum silicates
• Carboxymethylcellulose
• Silica thickeners Carrageenan
• Hydroxyethylcellulose
• Plant extracts (alginate, guar gum, gum arabic)
• Algae extracts (Carrageenan and Carbomer)
• Viscarine
• Xanthan gum
• Aniseed
• Clove oil
• Eucalyptus
• Peppermint
• Spearmint
• Fennel
• Vanilla
• Menthol
• Wintergreen
• Alcohols
• Benzoic acid
• Phenolics (methyl, ethyl, propyl)
• Ethyl parabens
• Formaldehyde Methylparaben
• Polyaminopropyl biguanide
ColorsSweetenersTherapeutic agents
• Chlorophyll
• Titanium dioxide
• Acesulfame
• Aspartame
• Saccharine
• Sorbitol
Anti-caries agents
• Fluoride
• Xylitol
• Calcium/Phosphate
• Sodium Bicarbonate
Anti-plaque agents
• Sodium Lauryl Sulfate (SLS)
• Triclosan
• Metal-ions
• Amyloglucosidase and Glucose oxidase
• Essential oils
• Chlorhexidine
Anti-calculus agents
• Pyrophosphate
• Zinc
Anti-dentine hypersensitive agents
• Potassium salts
Anti-halitosis agents
• Zinc
Whitening agents
• Abrasives
• Dimethicone
• Papain
• Sodium bicarbonate

Abrasive:

The primary function of abrasives is to remove plaque and stain from teeth. There are various abrasive agents used in toothpastes (Table 46.3). Almost 50% of toothpaste is made up of the abrasive agent. They are insoluble and help in plaque removal due to their abrasive action. These agents remove stains, polish the tooth surfaces and give a pleasing appearance to teeth.

Thickening / Binding agents:

These agents bind to water and control the viscosity of the toothpaste. They also prevent the toothpaste from drying out. They also give the toothpaste a creamy consistency. These agents have an emulsifying action, preventing the solid and the liquid substances from separating. These may be chemical compounds or natural plant or algae extracts (Table 46.3).

Humectants:

Toothpastes may become dry when they come in contact with air. Humectants are short-chained polyalcohols, added in the toothpastes to prevent loss of water and thus preventing drying of toothpaste. They also provide a creamy texture to the toothpaste. Most frequently used humectants are glycerine and sorbitol.

Solvents:

Water acts as a solvent in toothpaste, allowing all the contents to dissolve and make a uniformly thick paste. In preparations like mouth rinses, alcohol is used as a solvent which, along with acting as a solvent, also acts as a taste enhancer.

Surfactants:

Surfactants or detergents are important components of toothpastes. They produce…………

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

Sweeteners:

These are added in the toothpaste to provide it a mild sweet taste. The commonly used sweeteners include sodium saccharin, sorbitol, and glycerin. Toothpastes made for children are usually made sweeter than that for adults. Xylitol is a sweetener that is also claimed to provide anti-caries activity.

Flavoring agents:

These are the essential oils which have the primary action of masking the bad taste of surfactants and other agents and also to give a pleasant flavor to the toothpaste. Most commonly used essential oils as flavoring agents are spearmint, peppermint, eucalyptus, and menthol. These are dissolved into the toothpaste with the help of surfactants. Various flavoring agents are added to the toothpastes by different companies, according to the demand from the customers.

Coloring agents:

These provide an attractive color to the toothpaste. The Color Index is used to classify the color of the coloring agent. Titanium oxide and chlorophyll are the most commonly used coloring agents in the toothpastes.

Preservatives:

Preservatives are added to the toothpastes to prevent the growth of microorganisms. The most commonly used preservatives are sodium benzoate, methylparaben, and ethylparaben.

Therapeutic agents:

Various therapeutic agents can be added to impart a specific property to the toothpaste. The most commonly added therapeutic agent is fluoride, which prevents caries. Sodium fluoride (NaF) is most commonly used to make fluoridated toothpastes. Other agents used include mono-fluoro-phosphate (MFP) and stannous fluoride (SnF). The fluoride content in fluoridated toothpastes is between 0.10 – 0.15 %. Xylitol is another sugar alcohol, which cannot be fermented by oral microorganisms, hence is used as a cariostatic agent.

The commonly added anti-plaque agent in toothpastes is Triclosan. It is a synthetic non-ionic chlorinated phenolic agent with antiseptic qualities. It has an inhibitory effect on a broad spectrum of Gram-positive and Gram-negative microorganisms. It acts on the cell membrane of the microorganisms and causes cell death due to leakage of cellular constituents. Other metal ions used as anti-plaque agents are zinc (Zn2+) and stannous (Sn2+) ions. These ions inhibit the glycolytic sequence in oral anaerobic bacteria, thereby inhibiting their growth. Certain enzymes such as amyloglucosidase and glucose oxidase are also used as anti-plaque agents. They inhibit the growth of micro-organisms by activating the antibacterial lactoperoxidase-thiocyanate system in saliva 24. Essential oils such as thymol, menthol, eucalyptol and methyl salicylate also have anti-plaque effects. They exert their anti-bacterial activity by altering the bacterial cell wall.

Know more……………

Chlorhexidine (CHX) rinses combined with tooth brushing:

The majority of people do CHX mouth rinses immediately after tooth brushing. However, CHX rinses should not be combined with tooth brushing. The reason for that is…………………..

Content available in the book

Content available in the book

Content available in the book

Content available in the book

Content available in the book

Content available in the book

 

Anti-calculus agents added to the toothpastes exert their anti-calculus action by delaying dental plaque calcification 26. The commonly used anti-calculus agents are pyrophosphates (tetrasodium pyrophosphate, tetrapotassium pyrophosphate or disodium pyrophosphate). These have a high affinity towards the hydroxyapatite surfaces. By interacting with the tooth surfaces, they reduce the protein binding capacity of the tooth surface, hence delaying plaque formation. However, the plaque and salivary phosphatases enzymatically hydrolyze the P-O-P bond in the pyrophosphates. Hence, the effect of the anti-calculus activity of pyrophosphates lasts within a limited duration following toothbrushing.

Anti-dentinal hypersensitivity toothpastes are becoming increasingly popular these days. The most common anti-dentinal hypersensitivity agents used in toothpastes are potassium ions. These act by blocking the open dentinal tubules, thereby blocking action potential generation in intradental nerves 27.

Tooth whitening toothpastes are also becoming popular these days. It must be noted here that no therapeutic agent can change the natural color of the tooth. These agents, which are added to toothpastes for tooth whitening primary prevent staining of the teeth and help in the elimination of extrinsic and to some extent intrinsic stains on the teeth. Dimethicones which are………………….

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

Toothpastes manufactured nowadays, serve multiple purposes at the same time and, thus, possess a complex chemical composition. Again, it must be emphasized that the primary determinant of maintenance of dental and periodontal health is an accurate brushing technique rather than a toothpaste.

Table 46.4 Herbal toothpastes available in Indian market

Tooth paste type
Examples
Fluoridated ToothpastesPatanjali Dant Kanti
Colgate Herbal
Himalaya Complete Care
Neem Active
Non-Fluoridated ToothpastesHerbodent
Babool Neem
Meswak Complete Oral Care

Mouth rinses

As already discussed, the use of mouth rinses for good oral health and elimination of bad breath can be dated back to centuries. They are less complex than toothpastes and are used as an adjunct to mechanical plaque control. The ideal properties of a mouth rise are,

  • It should significantly reduce plaque formation.
  • It should exhibit the property of substantivity.
  • It should eliminate the pathogenic micro-organisms only.
  • It should be able to prevent the development of resistant bacteria.
  • It should not cause any adverse reaction with oral soft tissue.
  • It should not stain teeth or alter the taste sensation.
  • It should not react or have an adverse effect on dental materials.
  • It should be easily available, inexpensive and easy to use.

In presently availably mouth rinse formulations, ethyl alcohol is the most commonly used ingredient which stabilizes certain active components of the mouth rinse and improves its shelf life. However, the use of alcohol in mouth rinses has been suspected to have a possible correlation with the development of oropharyngeal cancer 28. Accidental ingestion of alcoholic mouthwash by children may cause convulsions, brain damage, or coma.  The alcohol in mouth rinses may also adversely affect the physical properties of certain restorations.

Sprays:

The spray is an effective way of delivering the therapeutic agent to a specific site. When applied accurately, sprays containing CHX have been used with almost equal efficacy as with CHX mouth rinses 29, 30. These are useful in case of physically or mentally handicapped children.

Oral irrigators:

The oral irrigators are very useful in the elimination of plaque and debris from the periodontal pockets. These function by producing a water jet with pressure in continuous or pulsated mode, thereby eliminating plaque and debris. A detailed description of oral irrigators has been given in the previous chapter on mechanical plaque control. The oral irrigators have been used to deliver a variety of chemotherapeutic agents for plaque elimination. Various investigations have analyzed the efficacy of CHX irrigation in reducing plaque. In one investigation usage of 0.2% CHX digluconate in a pulsated jet irrigator as part of daily dental home-care measures was analyzed. The results of the study demonstrated that 0.2% CHX used twice daily in an oral irrigator was effective at reducing plaque deposition, periodontal inflammation and probing pocket depths 31. Another study by Lang et al. (1981) 32 compared the plaque reduction efficacy of CHX digluconate (0.05%) used as a mouth rinse and in oral irrigators during experimental gingivitis. The study showed that the fractionated jet irrigator delivering CHX digluconate was most effective in plaque reduction. These findings were supported by a two-month experimental study where 44 subjects with at least 6 interproximal sites which bled on probing were randomly distributed on a double-blind basis into 4 treatment groups. These groups were placebo-rinse, CHX-rinse (0.12%), placebo-irrigation and CHX–irrigation (0.06%). The parameters were recorded at baseline and at 60 days. The results of the study demonstrated that gingivitis was significantly reduced in the group using an oral irrigator delivering CHX (0.06%) 33.

Varnish:

Various chemotherapeutic agents have been formulated in varnishes. These leave a thin layer of the active component on the applied surface which exerts its effect. CHX varnishes have been developed, however, their use is primarily restricted to prevent root caries rather than plaque control.

Detailed description of various chemical plaque control agents

First generation agents:

Phenols and essential oils:

Phenols and essential oils have a long history of use in the oral cavity as either mouth rinses or throat lozenges. The most well-known compound in this group is Listerine which has a long history of usage as an antiseptic agent. Listerine is made up of two phenol-related essential oils, thymol (0.064%) and eucalyptol (0.092%) mixed with menthol (0.042%) and methyl salicylate (0.060%), dispersed in a 21.6% – 26.9% hydroalcoholic vehicle. Many newer formulations have reduced alcohol content.

The history of Listerine goes back to 1860’s when an English doctor, Sir Joseph Lister applied Louis Pasteur’s theory that infections are caused by invisible germs, and pioneered antiseptic surgery. In 1865, he became the first surgeon to carry out an operation in a chamber sterilized by pulverizing antiseptic in the air. The mortality rates in the patients were markedly reduced with this asepsis procedure.  His work inspired Robert Wood Johnson and his brothers to start………………………….

123

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

However, when compared with CHX, essential oils are less efficacious in plaque reduction 41-43. One study demonstrated a 25% reduction in plaque by Listerine as compared to CHX (0.12%) which showed 75% reduction in plaque 41. Other studies were done to compare the comparative efficacy of Listerine®, Meridaol (amine/stannous fluoride solution), and CHX under an experimental gingivitis situation 44 and as an adjunct to routine oral hygiene 45 over a period of 3 weeks. The results of the studies demonstrated that Listerine was only 50% as effective as CHX in supragingival plaque reduction and development of gingivitis.

Triclosan, another phenol derivative which is chemically 2,4,4′-trichloro-2′-hydroxydiphenyl ether, has been used for years for making deodorants, soaps, and body powders. As with other phenolic compounds, it damages the bacterial cytoplasmic membrane, leading to the leakage of cellular components resulting in cell death. Its use as an anti-plaque agent has been studied and it has been shown to be 65% as effective as CHX 46, 47. Triclosan is non-ionic as compared to CHX and is compatible with dentifrice ingredients. It does not possess good substantial substantivity, however; if it is mixed in special formulations, its substantivity is increased 48. These include zinc citrate or the co-polymer, polyvinylmethyl ether maleic acid formulations 49. Triclosan is primarily used in toothpastes and has been studied for its anti-plaque and anti-gingivitis activity. Some studies have demonstrated no effect of triclosan-containing toothpastes over triclosan non-containing toothpastes in plaque or gingivitis reduction 50-53.  Other studies have shown a greater anti-gingivitis effect as compared to anti-plaque effect with the use of triclosan, which has been explained on the basis of its anti-inflammatory action 54.  Triclosan does not cause staining of the teeth as seen with CHX.

Metal salts:

Silver nitrate, zinc chloride, and bichloride of mercury were among the heavy metal ions initially investigated for their anti-plaque activity 7. The use of silver and mercury compounds in the oral cavity is limited because of the effects like tooth staining and soft tissue and systemic side effects. Zinc is the most commonly used heavy metal ion as an anti-plaque agent. The anti-bacterial action of zinc is attributed to its inhibitory effect on the conversion of glucose to lactic acid by inhibiting enzymes of glycolysis in bacteria. Zinc ions also inhibit the enzymes required for glucose uptake by S. sanguis and S. mutans. It is used in the form of zinc lactate, zinc citrate, zinc sulfate or zinc chloride. Zinc ions have been shown to have good substantivity. It has been demonstrated in one study that following toothbrushing with toothpaste containing zinc citrate, approximately 30% of total zinc citrate is retained in oral cavity 55. Gilbert and Ingramm (1988) 56 in one study showed that after brushing with 1 gm toothpaste containing zinc, 38% of the zinc was retained in the oral tissues. Also, increased levels of zinc were observed in bacterial plaque and saliva. In another study on mouth rinse containing 0.5% and 1% zinc citrate, Gilbert et al. (1989) 57 demonstrated an increase in the concentration of salivary zinc levels, which correlated with zinc citrate concentration in the mouth rinse.

Another heavy metal compound used as an anti-plaque agent is stannous fluoride. It has been used in dentifrices and gels since 1940s. The anti-bacterial action of stannous fluoride is attributed to its adherence to the bacterial surface, inhibition of bacterial colonization, penetration into the bacteria cytoplasm and interference with the bacterial metabolism 58. However, the major problem associated with its formulations is that it is not stable and its hydrolysis occurs in the presence of water 59. The most commonly used stable combinations of stannous fluoride are stannous fluoride and amine fluoride and 0.454% stabilized stannous fluoride, which may or may not be combined with sodium hexametaphosphate (SHMP). In a review, various studies have been highlighted which have demonstrated beneficial effects of different SnF2 formulations on the reduction in plaque accumulation and gingival inflammation 60. The stannous fluoride formulations have been shown to cause tooth staining, the mechanism of which is similar to that of CHX staining and staining caused by other cationic antiseptics which interact with dietary chromogens 61, 62. Other heavy metals such as copper also cause dental staining; however, its oral hygiene preparations are not available.

Natural Products:

Various natural products have been used for their anti-plaque action in the oral cavity. These include sanguinaria extract, propolis, chamomile, sage, myrrh, echinacea, rhatany and peppermint oil.

Sanguinarine:

Sanguinarine is commonly used anti-plaque and anti-gingivitis natural product. Chemically, it is a benzophenanthridine alkaloid derived from the alcoholic extraction of powdered rhizomes of the bloodroot plant, Sanguinaria canadensis 63. Following alcoholic extraction and purification, an orange powder is obtained which contains 30–35% sanguinarine. The anti-bacterial activity of sanguinarine is attributed to the chemically reactive iminium ions. It has been demonstrated that its concentration of 16 µg/ml completely……………..

123

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

Propolis:

Propolis is a naturally occurring honeybee product, resinous in nature. Honeybees collect propolis from the buds and exudates of certain trees and plants and use it to seal openings in their hives 73. It is a natural remedy and has been used extensively since antiquity. It was first used as an antiseptic, anti-inflammatory, antimycotic, and bacteriostatic agent by the Egyptians and then by the Greeks and Romans. The primary components of propolis are flavones, flavanones, and flavanols 74, 75. The most effective flavonoid agents against bacteria are galangin, pinocembrin, and pinostrobin. Other chemicals in propolis, which contribute to its antibacterial action are ferulic acid and caffeic acid 76.

Its usage has been advised in multiple oral conditions such as in stomatitis, orthodontic traumatic ulcers, halitosis, periodontal pocket / abscess, as a mouthwash, in the treatment of dentinal hypersensitivity, lichen planus, candidal infections and angular cheilitis. It has also been used as a pulp capping agent, in the treatment of dry socket and pericoronitis 77-82.

The efficacy of propolis as an anti-plaque and anti-gingivitis agent has been investigated. The propolis extract has been used as a mouth rinse in many studies 73, 83-86. Plaque inhibition by a propolis mouth rinse was compared to a positive and negative control in a double-blind, parallel, de novo plaque formation study design. CHX was significantly better in plaque inhibition as compared to propolis and the negative control group. The plaque inhibition in propolis group was marginally better than the negative control, but this difference was not significant 73. Because of its low effectiveness in plaque inhibition, its use as anti-plaque mouth rinse is limited.

Fluorides:

Fluorides primarily have anti-caries action. They do not possess anti-plaque or anti-gingivitis activity. However, stannous fluoride (SnF2) and amine fluoride demonstrate plaque inhibitory activity, particularly when they are combined together. Short-term studies have shown a significant reduction in plaque and gingival inflammation with the use of SnF2 mouth rinse 87, 88. However, long-term studies have demonstrated minimal beneficial effects of these agents in reducing plaque and gingivitis 89, 90. Furthermore, the plaque inhibitory action of these agents is derived from the non-fluoride portion of the molecule. Home use studies have shown their inhibitory effects against plaque and gingivitis 91-93, but it was less as compared to CHX. The only adverse effect associated with the use of stannous fluoride is a small amount of tooth-staining in some patients 89.

Antibiotics and Antimicrobial agents:

The primary etiology of periodontal diseases is microbial. For this reason, the systemic and local use of antibiotics and antimicrobial agents has been a matter of discussion for a long time now 94. Antibiotics and antimicrobial agents are not indicated for the control of plaque and gingivitis, but they may be used as adjuncts in the treatment of other periodontal diseases. Three topical antibiotics have been evaluated for their anti-plaque and anti-gingivitis action. These are niddamycin, vancomycin, and kanamycin 95-97. However, the side effects of these antibiotics and antimicrobials are of great concern when they are used for long term. Even when they are used locally, few side effects can be seen. Most important of these side-effects is the development of antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) which may cause serious life-threatening infections.

Quaternary ammonium compounds:

The quaternary ammonium compounds have been widely used in food, water treatment, and the textile industry because of their relatively low toxicity and broad antimicrobial spectrum. Cetylpyridium chloride (CPC) and benzalkonium chloride are the most studied compounds in this group. These compounds are……………………………….

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

The positively charged hydrophilic region is primarily involved in its antimicrobial activity. The interaction of the hydrophilic region with bacterial cell membrane disrupts its integrity which causes leakage of cytoplasmic components, interfering with cellular metabolism, inhibition of cell growth and cell death 101-103. Two commercially available CPC preparations are Cepacol and Scope, with concentrations of 0.05% and 0.045% CPC, respectively. In addition to CPC, Scope contains 0.005% domiphen bromide.

Various short and long term studies have evaluated the anti-plaque and anti-gingivitis properties of quaternary ammonium compounds. The short-term studies have reported an average plaque reduction of 35% with mixed effects on gingival health 104-106. One six month trial investigated the anti-plaque and anti-gingivitis activity of CPC. The results of the study reported a 14% reduction in plaque and a 24% reduction in gingivitis 107. Pre-brushing CPC mouth rinse as an adjunct to mechanical oral hygiene was investigated in one study for its effects on plaque accumulation. The results of the study showed addition benefits of CPC pre-brushing mouth rinse on plaque accumulation 108. The side effects reported with the use of quaternary ammonium compounds as mouth rinses include tooth staining, mucosal ulceration and discomfort 3.

Although, quaternary ammonium compounds have substantial anti-plaque and anti-gingivitis activity, but they are less efficient than CHX, which limits their use.

Oxygenating agents:

Oxygenating agents such as hydrogen peroxide (H2O2) and buffered sodium peroxyborate and peroxycarbonate have been investigated for their use as anti-plaque and anti-gingivitis mouth rinses. Hydrogen peroxide has been used for a long time for cleaning the oral tissues, but its use an anti-plaque or anti-gingivitis agent is limited. Another problem with H2O2 is that it is unstable and difficult to formulate and store in concentration acceptable for human use (<3%). H2O2 is effective in the inhibition of anaerobic bacteria which are involved in the development of gingivitis and periodontitis 109.

Various short and long term studies have revealed unimpressive results with regard to their use as anti-plaque and anti-gingivitis agents 110-113. Further, H2O2 in a concentration of 3% has been shown to increase the tissue injury in existing wound and delay wound healing, which raises its safety concern 114, 115. Finally, the efficacy of H2O2 in a concentration of less than 3% in plaque and gingival inflammation reduction is less as compared to CHX, which limits its clinical use as a mouth rinse.

Enzymes:

The enzymes used for anti-plaque activity can be divided into two categories: enzymes that disrupt the early plaque matrix and enzymes that enhance the host defense mechanism. The first group contains enzymes such as dextranase, mutanase and various other proteases which disrupt the plaque matrix. In the late 1960s and early 1970s, these enzymes were analyzed for their anti-plaque action. However, their poor substantivity and local side effects such as mucosal erosion, limited their use as an anti-plaque agent. In two studies dextranase was evaluated for its anti-palque activity, but the results were disappointing 116, 117. Mutanases, another enzyme which inhibits bacterial adhesion to teeth showed beneficial results against plaque, but caused adverse effects to oral soft tissues 118, 119.

The second group of enzymes included glucose oxidase and amyloglucosidase that act to enhance the host defense system by catalyzing the synthesis of hypothiocyanite from thiocyanate through the salivary lactoperoxidase system. The hypothiocyanite has an inhibitory effect on the bacterial metabolism, thus exerting its anti-bacterial action. However, when hypothiocyanite was added to toothpaste and its clinical evaluation was done for its anti-plaque activity, the results were disappointing 120-123. No long-term (6-month) studies are available to support the long term use of enzymes as anti-plaque or anti-gingivitis agents.

Surfactants/Detergents:

Sodium lauryl sulfate (SLS) is the most common component of toothpastes and mouth rinse products. Because of its detergent action, SLS exerts its antimicrobial action by acting on the bacterial cell membrane 124 SLS has moderate substantivity between 5 to 7 hours in the oral cavity which is almost similar to triclosan 124, 125. Mouth rinses containing only SLS are not available commercially and there are no long-term studies supporting their usage for a long duration.

Second generation chemical plaque control agents

Bisbiguanides:

Bisbiguanides are a class of chemically related organic compounds which are known for their bactericidal properties. This group of chemical compounds contains agents like chlorhexidine, alexidine, and octenidine. CHX is presently the most widely used anti-plaque and anti-gingivitis agent.

Chlorhexidine (CHX):

Presently, CHX is the most effective anti-plaque and anti-gingivitis agent. It is effective against Gram +ve and Gram -ve bacteria as well as against facultative aerobes and anaerobes 126-128. It has also been shown to inhibit the growth of yeast and fungi 129. Although CHX is not considered virucidal, but it shows some activity on the lipid envelopes of viruses such as HIV, Herpes 1 and 2 and Influenza A 130. Structurally, it is a cationic poly-biguanide (bisbiguanide) and is used primarily as its salts, dihydrochloride, diacetate, and digluconate because the base molecule is relatively insoluble in water.

Historical aspect:

CHX has been used for more than 60 years as an effective plaque control and anti-gingivitis agent. This chemical compound was first discovered by the Imperial Chemical Industries, Limited (Manchester, UK) in 1950 while researching the synthesis of anti-malarial agents 131. Davis et al. (1954) 126 found that a bisbiguanide with a chemical structure 1,6 bis-4 chloro, phenyldiguanidohexane had the greatest bacteriostatic and bactericidal properties. In 1954, they published an article, entitled “1:6-Di-4′-Chlorophenyldiguanidohexane (“Hibitane”). Laboratory Investigation of a New Antibacterial Agent of High Potency” In the same year, CHX gluconate was registered by Imperial Chemical Industries Co. Ltd of Macclesfield (United Kingdom) as Hibitane®, the first internationally accepted antiseptic for cleansing wounds and the skin. In 1957, Chlorhexidine digluconate was first introduced commercially in the United Kingdom as a disinfectant and topical antiseptic. In the United States, it was first introduced commercially in 1970’s as a disinfectant and topical antiseptic under the name “Hibiclens”, which is 4% CHX gluconate solution primarily used as an antimicrobial skin cleanser. Löe and Schiött (1970) 132 were first to demonstrate the anti-plaque property of CHX, when they introduced 0.2% CHX gluconate mouth rinse and in an experimental gingivitis study, demonstrated that twice or even once oral rinses with 10 ml of 0.2% CHX rinses for 60 seconds prevented plaque growth and development of gingivitis over a period of 21 days in which no oral hygiene measure were used. The first study, which evaluated the application CHX mouth rinse with toothbrushing was carried out by Flotra et al. 133 in 1972, who on a group of soldiers used twice daily CHX mouth rinses along with tooth-brushing for a period of 4 months. The authors reported 66% reduction in plaque and 24% reduction in gingivitis. Since then, numerous studies have been done on CHX which have proved its anti-plaque and anti-gingivitis efficiency and presently, it is considered as the gold standard anti-microbial agent, against which the effectiveness of various other anti-plaque and anti-gingivitis agents is assessed.

Chemical structure:

Structurally, CHX molecule is an amphipathic molecule with both hydrophilic and hydrophobic groups. It is cationic at physiological pH. CHX is made up of two symmetrical chlorophenol rings (4-chlorophenyl) and two biguanide groups, united by a central hydrophobic hexamethylene chain. As already stated, CHX is used in salt form because of the relative insolubility of the base molecule. In the majority of mouth rinses, gels and varnishes digluconate salt is used because it is most water and alcohol soluble.  Because of the highly cationic nature of CHX, it is difficult to formulate in dentifrices due to the risk of inactivation of the CHX molecule with other anionic ingredients.

Mechanism of action of CHX:

CHX has a broader antibacterial spectrum as well as quicker killing rate than many other antimicrobials 134. CHX is a membrane active agent. The primary action of CHX is…………………………….

123

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

The bacteriostatic and bactericidal concentrations of CHX vary for different bacterial species. CHX is more effective against Gram +ve bacteria (≥ 1 µg/l) as compared to Gram -ve bacteria (10 to >73 μg/ml) due to the difference in their cell wall structure 143.

Figure 46.1 Mechanism of action of chlorhexidine (CHX).

Mechanisms of plaque inhibition by CHX:

There may be multiple mechanisms of plaque inhibition be CHX. Most of the authors 144, 145 have proposed three mechanisms of plaque inhibition be CHX,

  1. The blocking of salivary glycoproteins by CHX prevents their binding to the tooth surface, hence inhibiting the acquired pellicle formation.
  2. Another proposed mechanism of CHX mediated plaque inhibition is………..

123

  1. The third proposed mechanism of CHX is that it may compete with calcium ion agglutination factors in plaque, as it has been shown that CHX may bind to hydroxyapatite on the tooth structure 147. However, this interaction is of less significance because CHX primarily attaches to acidic proteins in pellicle, plaque, bacterial cell membranes and oral mucosa 148.
Know more…………..

0.12% and 0.2% preparations of CHX:

One of the primary disadvantages of CHX is staining of teeth and soft tissue because of its affinity for dietary compounds, some of which cause staining 149. Sometimes, this staining is so severe that professional prophylaxis is required to remove these stains. Also, tongue brushing may be required to remove the stains from the surface of the tongue 150. Another major side effect of CHX is the altered taste sensation. To overcome these side effects of CHX, its lower concentrations have been formulated such as Peridex (0.12% CHX) and Eludril (0.1% CHX). In one experimental study staining of acrylic specimens were evaluated following the application of 0.2% and 0.1% CHX preparations. The results of the study demonstrated heavy staining with 0.2% CHX whereas 0.1% CHX produced no staining of acrylic specimens greater than that of controls. The anti-microbial effects of both the preparations were similar. The overall activity of CHX in 0.1% CHX preparation was partially or completely inactivated, which, according to the authors was because of the presence of detergent. The authors further stated that the anti-microbial activity of the solution (0.1% CHX) was derived more from the detergent than CHX 151. These findings were supported by another short-term single-blind crossover study in which 0.2% (Corsodyl) and 0.1% (Eludril) preparations of CHX were used on a group of 14 volunteers. During the course of the study, observations were made for plaque formation, gingivitis, and staining. The authors reported significantly less gingivitis in 0.2% CHX group at 12 and 19 days as compared to 0.1% CHX group, but staining was markedly reduced in 0.1% CHX group. The authors concluded that the reduced anti-plaque activity in lower CHX concentration preparation was due to some components in its preparation which inactivated CHX 152.

 

Some other authors have preferred 0.1% CHX preparation over 0.2% CHX preparation as a prophylactic mouth rinse after oral surgery because of its better patient acceptance and fewer side effects  153.

 

Pharmacokinetics and Pharmacodynamics of CHX in the oral cavity:

The local application of CHX in the form of mouth rinses or irrigation follows principles of first order kinetics, where high initial concentrations of the agent along with multiple applications are required to provide sustained effectiveness. To improve the sustained release of CHX, controlled delivery systems have been designed. Controlled drug delivery system was proposed by Judah Folkman in mid-1960’s. In this system, the drug is released in a controlled manner when a polymer, whether natural or synthetic, is judiciously combined with a drug or other active agent in such a way that the active agent is released from the material in a pre-designed manner 154. The basic components of a controlled delivery system are drug reservoir, the rate-controlling element, and biological platform. These systems are the basis of local drug delivery. Periochip® is CHX chip placed in the periodontal pockets for sustained release of the active agent (discussed in detail in “Local drug delivery in periodontics”).

Since most of the surfaces in the oral cavity are negatively charged; CHX gets well dispersed in the oral cavity. Also, due to its high affinity towards negatively charged surfaces, it is not easily displaced and stays for a longer duration of time which accounts for its good substantivity 155. The attached CHX molecules are slowly displaced by the calcium ions in saliva. However, its high affinity towards negatively charged surfaces is not only responsible for its efficacy, but also contributes to its side effects 156.

The substantivity of CHX depends on its concentration used, rinsing time, temperature and pH 98. 157. 0.2% and 0.12% concentrations of CHX are widely used in mouth rinses.  CHX does not penetrate the oral mucosa and most of it is retained on the oral surfaces primarily bound to glycoproteins. The interactions between surface glycoproteins and CHX are electrostatic in nature, reversible and pH dependent 158. Basic pH favors the retention of CHX in the oral cavity. It has been demonstrated that retention of CHX to oral surfaces is inhibited by lowering the pH of the rinsing solutions (pH=3), resulting in a reduced plaque inhibition 159.

CHX has a good substantivity in the oral cavity and most of the studies have shown its substantivity up to…………..

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

Synergistic effect of CHX with other agents:

CHX has been shown to have synergistic effects when combined with some other agents. The addition of fluoride or thymol in CHX containing varnish has been shown to increase the anti-caries activity of varnish 171. The combination of CHX and copper (Cu2+) has been shown to be synergistic in inhibition of growth of Streptococcus mutans, Actinomyces viscosus, and Actinomyces naeslundii 172. Low concentrations of CHX combined with copper (Cu2+) can be used in a rinse form to reduce caries risk as well development of gingivitis. Another synergism reported with CHX is with zinc ions. One study reported that Porphyromonas gingivalis proteinases (gingipains) were effectively inhibited by CHX and the inhibitory effects of CHX were enhanced 3 to 30-fold by Zn ions 173. CHX has also been shown to act synergistically with ozone in root canal disinfection. The study reported that application of 2% CHX followed by application of ozone gas for 24 seconds promoted the complete elimination of Candida albicans and Enterococcus faecalis 174. Another study reported the synergistic action of CHX and hydrogen peroxide against Enterococcus faecalis when used as an intracanal irrigant 175.

CHX delivery systems:

The CHX formulations are available in various formulations such as mouth rinses, gels, sprays, toothpastes and chewing gums.

Mouthrinses:

These are the most commonly used formulations of CHX. Most of the commercially available formulations contain CHX gluconate solution in a suitable flavored and colored vehicle. The mouth rinses are available in 0.12% or 0.2% CHX concentrations. CHX is bitter in taste and various agents are added in the mouth rinses to make its taste acceptable to the patients. However, masking of the taste by the addition of various agents is also associated with the decreased activity of CHX.

Gels:

The CHX preparations in gel form are effective formulations for plaque control, especially in handicapped individuals 176. These can be delivered with the help of a toothbrush or tray. CHX gels are available in both 0.12% and 0.2% preparations. 2% gel formulation of CHX has also been shown to be an effective root canal lubricant. However, the gel formulation required significantly more time for killing microorganisms as compared to the corresponding concentration in liquid form 176.

Sprays:

Both 0.1% and 0.2% CHX sprays are available commercially. These are very useful in physically and mentally handicapped patients. It has been shown that twice daily spray of non-aerosol CHX delivers approximately 1.4 to 2 ml of CHX which is one-seventh of the optimal mouth rinse dose of 0.2% CHX. However, the effects on plaque and gingival bleeding observed in both cases were the same 28.

Toothpastes:

As already stated, CHX formulation in toothpastes is associated with the problem of CHX inactivation due to its highly cationic nature because of which it can bind to the components in the toothpaste. CHX is inactivated by sodium lauryl sulfate (SLS) which is commonly used as a surfactant in toothpastes. However, toothpastes with high active CHX availability have been formulated and tested for their anti-plaque, anti-gingivitis effectiveness 177. An example of CHX containing toothpaste is Cariax® which has 0.12% CHX.

Chewing gums:

Chewing gums are an effective method for delivering various topical dental prophylactic and therapeutic agents. Chewing gums containing various therapeutic agents such as fluorides, xylitol, metal salts, enzymes and CHX diacetate have been made commercially available by various companies. Most of the CHX containing chewing gums have been formulated in such a way that they deliver unbound active CHX molecules. These are particularly indicated in patients with xerostomia and malodor. It may also be advised as an adjunct to routine mechanical plaque control in patients undergoing treatment for active periodontal diseases. The patient may be advised to chew 4-6 pieces of chewing gum daily for approximately 20 minutes. One chewing gum contains  5mg of CHX, so 20- 30 mg of CHX is delivered in a day 28. The contraindication for using CHX containing chewing gum is hypersensitivity to CHX or any other component of the chewing gum.

Varnishes:

Varnishes are an effective way of professionally delivering therapeutic agents. It does not require patient’s compliance and the effects can be monitored by the operator. They do not cause discoloration and staining. Presently, commercially available CHX varnishes are EC40, Chlorzoin and Cervitec 178. The advantage of varnish application is that it can provide sustained delivery of CHX, however, it requires repeated application of the varnish 178. Further, it provides caries prevention benefits similar to that of topical fluoride applications in the permanent teeth of teenagers 179. These are also beneficial in preventing root surface caries 180. The application of subgingival CHX varnish in conjunction with root planing has been shown to reduce pocket depth at initially deep sites 181.

Side effects of CHX:

Various side effects associated with the use of CHX are, brown discoloration of the teeth, restorative materials and dorsum of the tongue, taste perturbation, increased calculus formation, sometimes there can be dose dependent oral mucosal erosion which is an idiosyncratic reaction and parotid swelling 2, 182, 183.

CHX staining:

The long term use of CHX is associated with staining. The CHX stains are yellowish brown and can be seen on the teeth, dorsum of the tongue, composite restorations and on artificial teeth. The possible mechanisms involved in CHX associated staining include non-enzymatic browning……………………………………………….

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

Another proposed mechanism of CHX associated staining is the formation of the pigmented sulfides of iron and tin. It has been suggested that CHX denatures the pellicle because of which the sulfur radicals are exposed. These exposed sulfur radicals react with metal ions to form the metal sulfides responsible of discoloration. Iron and tin ions have been shown to be particularly associated with the formation of metal sulfides. In a study, Warner et al. (1993) 189 showed that levels of iron and sulfur were increased in subjects treated with CHX as compared to water controls. The authors concluded that the chromophore was not a sulfide, but sulfur containing organic compound and metal ion complex. The authors also stated that deposition of sulfate proteins was accelerated by CHX.

Many clinical studies have suggested that staining is caused by the interaction or precipitation of dietary chromogens with locally adsorbed CXH 190-192. The CHX can react with polyphenols in dietary substances to produce staining. It has been shown that in the presence of food components, CHX dyes produce colored compounds on hydroxyapatite 193. Tea, coffee, and red wine have been found to be particularly chromomeric when used with CHX 194.

 

Know more……..

CHX associated staining theories, which are no longer accepted:

There are two proposed mechanisms of CHX associated staining which are no more accepted. According to the first mechanism, the breakdown of CHX in the oral cavity resulted in the formation of parachloroaniline which was proposed to cause staining 195. Parachloroaniline also has carcinogenic potential 196. The other mechanism proposed was reduced bacterial activity due to CHX which resulted in partly metabolized sugars which were broken down and then degraded over time to produce brown-colored compounds 197.

 

 

Taste disturbance (dysgeusia):

The aqueous solution of CHX is very bitter which causes altered taste perception. The major taste perceptions being affected are sweet and salt 198. The bi-cationic nature of the CHX molecule which is responsible for its antimicrobial activity seems to be associated with taste disturbance. This taste disturbance is thought to be caused by denaturation of surface proteins on the taste buds by CHX molecules. The altered taste sensation is transient and it returns to normal after the cessation of the drug.

Oral mucosal erosion, which is an idiosyncratic reaction:

Occasionally, burning sensation and painful desquamative lesions on oral mucosa have been reported. The reason for these oral lesions seems to be precipitation of the mucin layer with a resultant reduction in its lubricating effect 199. These reactions are dose dependent and resolve afterthe cessation of the drug.

Increased calculus formation:

The exact mechanism of increased calculus formation with………………..

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

Unilateral or bilateral parotid swelling:

This is a rare side effect of CHX where unilateral by bilateral parotid swelling is observed. The exact mechanism of the precipitation of this condition has not been explained well. However, the involvement of viral infection (parotitis) in connection with CHX mouth rinses has been suggested by some authors that might be co-incidental, but cannot be completely disregarded 133. Another explanation is the inhibition of antiviral activity of secretory IgA. The secretory IgA accumulate on the mucous membrane and probably the precipitation of acidic proteins in the mucin layer which coats the mucous membrane may interfere with the anti-viral activity of IgA 201.

Another proposed cause of CHX associated parotid gland swelling is vigorous rinsing. Vigorous rinsing may cause the CHX to enter the parotid duct, which may lead to an inflammatory reaction involving the duct wall and the gland parenchyma. Due to the inflammation, there may be narrowing of the duct lumen and thus transient obstruction in salivary flow 202.

Uses of CHX other than mouth rinses:

CHX is a very effective anti-microbial agent. It has many uses in dentistry other than mouth rinses. These are,

  • It is used for disinfecting hands, skin and washing the wounds.
  • It is used in chemical sterilization.
  • As an endodontic irrigant. 0.2 % CHX can be used as an endodontic irrigant and intracanal dressing.
  • It has been used to reduce the severity of gingival overgrowth.
  • Application of bioadhesive2% CHX gel in the socket after 3rd molar extractions can help in reducing the chances of alveolitis (dry socket).
  • Treatment of dental unit water lines with 0.12% CHX gluconate reduces bacterial load in dental unit waterlines.
  • Pre-treatment rinses with 0.2 or 0.12% CHX are effective in reducing bacterial aerosols.

Third generation agents

Delmopinol:

Delmopinol is a low molecular weight, surface active compound which is chemically, 3-alkyl substituted N-hydroethyl morpholine. It belongs to the amine alcohols and the other agent in this group is octapinol. Delmopinol has demonstrated good potential as a mouth rinse for the management of dental plaque and treatment of gingivitis. Its mechanism of action is through inhibition and disruption of the biofilm extracellular matrix. In other words, it is not an anti-microbial agent because it disrupts already established biofilm. Delmopinol has been shown to inhibit glycan synthesis by streptococcus mutans 203, 204. Its application results in……………………………………

123

123

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

Another study showed that daily rinsing of 0.1%, 0.5% and 1% of delmopinol reduced 16%, 56% and 56% of mean plaque extension and significantly reduced the mean gingival index when compared to the placebo 205.

When compared with 0.2% CHX, 0.2% delmopinol showed a comparable reduction in plaque scores. However, the reduction in gingivitis was similar to that of placebo mouth rinse, doubting its anti-gingivitis efficacy 206.

Delmopinol has been incorporated in various products such as mouthwash, sprays, toothpastes and lozenges. The major side effect associated with long-term use of delmopinol is transient tingling and numbness of the tongue or other parts of the oral mucosa 206-208.

Other agents

Salifluor:

Chemically, salifluor is 5 N-oetanoyl-3’trifluormethylsalieylanilide. It is a broad spectrum antimicrobial agent and has been investigated for its ability to inhibit dental plaque formation. It has demonstrated excellent activity against a wide variety of Gram-positive and Gram-negative oral microorganisms, including Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and Tenerella forsythia 209. Salifluor also possesses anti-inflammatory properties 210. However, the mechanism involved in the anti-microbial and anti-inflammatory properties of salifluor has not been understood completely. Studies have shown the significant anti-plaque activity of salifluor as compared to placebo controls 211, 212. Further, the anti-plaque activity of salifluor mouth rinses and CHX 0.12% was found to be similar 211. Salifluor is a relatively newer anti-plaque and anti-gingivitis agent which requires further investigations before it can be used as a routine chemical plaque control measure.

General indications for mouth rinses

Oral malodor:

The most common indication for the use of mouth rinses is oral malodor. Many chemical plaque control agents such as CHX, CPC, essential oils, triclosan etc. reduce the volatile sulfur-producing bacteria in the oral cavity, thus reducing oral malodor. These agents must be differentiated from mouth fresheners which do not kill the micro-organisms causing malodor.

Anti-plaque agents:

Although, mechanical plaque control is the primary method for controlling plaque accumulation, chemical plaque control agents may be used as an adjunct to mechanical plaque control. It must be remembered that chemical plaque control agents should not be advised to each and every patient. Those patients, who are not able to maintain an adequate oral hygiene due to any reason or patients with periodontal diseases, may be advised to use these agents. The most commonly used anti-plaque agent is CHX.

Anti-gingivitis:

Gingivitis is the result of plaque accumulation and resultant inflammation due to host-bacterial interaction. Adequate mechanical plaque control is the primary measure to reduce gingivitis. However, some mouth rinses may be advised to the patient to control gingival inflammation, including essential oils (Listerine), CHX etc.

Calculus control:

In high calculus formers, agents which reduce the calculus formation are useful. These contain ingredients like zinc chloride, which retards calculus formation.

Anti-caries:

Patients with high caries risk may get benefited from the use of mouth rinses congaing fluorides. Fluoride preparations such as sodium fluoride, acidulated phosphate, stannous fluoride or combination of fluoride sources may be advised in these patients.

Conclusion

Chemical plaque control measures are widely used for controlling plaque formation and preventing the development of gingival inflammation. Dentifrices are the most commonly used chemical plaque controlling agents, used in combination with tooth-brushing. Along with providing clean teeth, they also provide fresh breath. The therapeutic agents added in dentifrices also help in reducing incidences of caries and periodontal diseases. Mouth rinses are commonly used for the prevention of halitosis with CHX formulations being the most commonly available over the counter mouth rinses worldwide. Although various mouth rinses have shown their anti-plaque and anti-gingivitis effects, they cannot be used alone as monotherapy to control plaque but are used in conjunction with mechanical plaque control. The regular use of mouth rinses is associated with some side effects. Presently, CHX is considered as gold standard for chemical plaque control, but it does not fulfil all the qualities of an ideal anti-plaque and anti-gingivitis agent. More research is required to formulate a chemical plaque control agent which is better than CHX and fulfills most of the requirements if not all, of an ideal chemical plaque control agent.

Periobasics: A textbook of Periodontics and Implantology
For India Users:
Buy Now
For International Users:

References:

References available in the hard copy of the website

Periobasics: A textbook of periodontics and implantology.

Leave a Reply

You must be logged in to post a comment.