Chlorhexidine, chemical composition, clinical application and its effect on the strength and durability of enamel and dentin bonding (part one)

Thymol, eucalyptol, hextidine, methyl salicylate, menthol, chlorhexidine gluconate, benzalkonium chloride, cetylpyridinium chloride, methyl paraben, hydrogen peroxide, diphen bromide, enzymes and sometimes fluoride and calcium. Water is also a component that keeps the above components together. Sweeteners such as sorbitol, sucralose, sodium saccharin and xylitol, which have an antibacterial effect, may also be added. Sometimes alcohol is added up to 20% as a carrier of flavoring agents; In addition, alcohol also exerts its antibacterial properties. Of course, alcohol can cause dryness and dehydration of the oral environment and exert its carcinogenic effects in case of frequent consumption. Many new chlorhexidine mouthwashes do not contain alcohol.

A preservative such as sodium benzoate is added to most mouthwashes to keep the mouthwash fresh after the lid is opened.

Many mouthwashes have an acidic pH. In people who have acid reflux or have digestive problems, it is recommended to use mouthwashes with neutral pH.

● Function
Chlorhexidine is a bisbiguanide compound with a similar molecule, which is highly cationic. Chlorhexidine is a bacteriostatic drug and bacteriocide. This substance is a strong antiseptic against Gram-negative and Gram-positive bacteria. The important point is that chlorhexidine can also affect the lipid and protein membrane of Gram-negative bacteria.

Chlorhexidine exists in three forms: digluconate, acetate and hydrochloride, of which two forms, digluconate and acetate, are soluble in water. One of the advantages of chlorhexidine is its strong connection and adhesion to most areas of the mouth, which causes this substance to be released gradually and slowly after adhesion, and in a period of time, it constantly provides an antimicrobial environment in the mouth.
Approximately 30% of consumed chlorhexidine remains on the surface of the mouth and its buffer release varies depending on the pH of the mouth. The reason for the stickiness of chlorhexidine is attributed to its cationic property, which causes it to bind to the anionic groups present in glycoproteins and phosphoproteins on the surface of the mucous membrane and oral pellicle. The effect of chlorhexidine is not limited to a specific species and is effective on a wide range of gram-positive and negative bacteria, as well as some fungi and some viruses, including the virus that causes AIDS and hepatitis.
Due to its cationic property, its skin and mucous absorption from the digestive system is minimal. In animal experiments, toxic and carcinogenic effects have not been seen in this substance.
Most researchers are of the opinion that the mechanism of action of chlorhexidine is related to the strong tendency of this substance to adhere and bind strongly to the membrane of bacteria and tear the cell membrane. After the chlorhexidine molecule binds to the bacterial membrane, the permeability of the said membrane increases and due to the disruption of the osmotic balance on both sides of the cell wall, some of the intracellular contents with low molecular weight leave the cell. This phenomenon occurs in the presence of low amounts of chlorhexidine, while in higher amounts, this substance is deposited in the cystoplasm.

● Available commercial forms:

Chlorhexidine is available in the form of mouthwash, varnish, gel or in chewing gum. Its gel is recommended for people with high caries risk; In this way, it is used once a week with a toothbrush. The concentration of chlorhexidine gel is 1%.

Chlorhexidine varnish is also available. Acceptable concentrations of chlorhexidine in varnish are 0.1-0.2%. Fluoride varnish remains on the teeth for at least 24 hours. For this reason, its effect is more than other methods, and on the other hand, it causes the teeth to look ugly, which will last up to 24 hours. Another disadvantage of fluoride varnishes is its bitter taste.

Chlorhexidine mouthwash is available under the trade names Pridex, Priochip Towelette, Periogard, Perisol, Spectrum-4, and Oral rinse. In England it is available as Corsodyl or Chlorhex. In Germany it is known as Chlohexamed and in Australia it is named Sevacol. In some countries, it is known by its medicinal name, chlorhexidine. In Iran, chlorhexidine, which is available to the public in pharmacies, is 0.2% chlorhexidine; Of course, recently 0.12% chlorhexidine has also been introduced, which according to the manufacturer’s claim, its side effects such as discoloration of teeth are much less than similar types (with higher concentrations). Chlorhexidine mouthwash is not recommended for children under 6 years old.

Chlorhexidine, which is available in dental offices, is pure and does not contain additives necessary to create a mouthwash. Chlorhexidine 0.12% (Ultra dent) is provided to disinfect the cavity before restoration. Chlorhexidine 2% (FGM) is also available in the dental market, which, due to its high concentration, has very strong bactericidal and bacteriostatic effects, which can be used to wash the canals or disinfect the cavity before restoration. Of course, due to its high concentration, it has a burning effect on the mucous membrane, and for this reason, it is not recommended to use it as a mouthwash.

A new mouthwash named Epimax has entered the market. This mouthwash contains 0.12% chlorhexidine and 0.05% sodium fluoride and does not contain any alcohol.

It should be noted that the highest concentration of chlorhexidine available is 4%, which is used to disinfect the surgical environment. Its 2% concentration is used to disinfect hands. Its concentration of 2% and 4% can inhibit bacteria, fungi, yeasts and viruses.

· Gums containing chlorhexidine:

Gum is accepted as a standard pharmaceutical form and its name was registered as a pharmaceutical system in 1991 in the European Commission. The medicinal form of chewing gum is of interest due to the reduction of the drug dose, the reduction of side effects, the controlled release of the drug in a relatively long time, the stimulation of salivary secretion and the creation of a buffering effect, and the ease and attractiveness of consumption, etc. Ainamo and Etemadzadeh showed that gum can be a good carrier for chlorhexidine. It has been shown that the anti-plaque properties of gums containing chlorhexidine are higher than those containing xylitol and sorbitol. Gums containing chlorhexidine and xylitol significantly reduce the amount of pathogenic bacteria streptococcus mutans and lactobacillus and yeasts in the oral cavity; But gums containing xylitol only reduce the amount of Streptococcus mutans. Chlorhexidine gum has anti-gingivitis properties and the amount of tooth discoloration caused by it is significantly less than chlorhexidine mouthwash. In some studies, consumer satisfaction with the taste of chlorhexidine gum has been reported to be weak; Therefore, it seems necessary to present a new formula in order to achieve the desired taste for public consumption at the community level. The study of Dr. Kalahi, Dr. Ghaliani and Dr. Varshusaz showed that gum can be a good carrier for chlorhexidine gluconate. In this system, the drug was released over a relatively long time and in a controlled manner, which is preferable to the mouthwash form that is used for only 30 seconds. The amount of drug released in chlorhexidine gums is equal to 20 mg per day, which is half of the mouthwash form (40 mg per day). The results of this study showed that chewing gum containing chlorhexidine gluconate can completely prevent the formation of dental plaque; In addition, it can reduce the amount of plaque.

The most important concern about using chlorhexidine gums is their safety. A review of the 20-year use of chlorhexidine shows that this substance has no carcinogenic effects in laboratory animals and its long-term oral use has not caused any changes in hematological and biochemical indicators in humans. Chlorhexidine is hardly absorbed from the skin, mucous membrane and digestive system and shows little toxicity. In addition, the amount of drug in each piece of gum is very small, so there does not seem to be any concern about swallowing the drug content of the gum.

Therefore, due to the safety and effectiveness and many benefits, including reducing the amount of medicine by half, reducing side effects, stimulating saliva secretion, increasing the buffering effect, long-term and controlled release of the drug, this type of gum can be used as an important component in promoting Oral and dental hygiene should be recommended to patients.

· Glass ionomers containing chlorhexidine:

In a study conducted in 2005, it was shown that the best concentration of chlorhexidine for glass ionomer is 1%. In this concentration, bacteria will be inhibited and will have the least impact on the physical properties and bond strength of glass ionomer; While higher concentrations decrease the tensile strength and compressive strength of glass ionomer. This concentration has no negative effect on the setting time of chlorhexidine.

Two chlorhexidine salts (chlorhexidine diacetate and chlorhexidine dichloride) are in powder form and can be added to glass ionomer powder.

●Application of chlorhexidine to mix MTA

Although the direction of mixing MTA Physiological serum or anesthesia can be used, but the use of chlorhexidine gluconate 0.12%, antibacterial effects MTA strengthens. While MTA mixed with water also inhibits bacterial growth; But replacing chlorhexidine instead of water is more effective and can inhibit bacteria such as Actinomyces odontolyticus, Fusobacterium nucleatum, Streptococcus sanguinis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans.

۲% chlorhexidine can be used instead of 0.12% chlorhexidine; However, the use of 0.2% chlorhexidine mouthwash is not recommended due to impurities such as alcohol.

● Chlorhexidine and the reduction of caries-causing bacteria:

Various antibacterial agents such as antibiotics have been considered to reduce caries-causing bacteria. In the meantime ; In addition to fluoride, chlorhexidine has had a significant effect in reducing caries-causing bacteria. Chlorhexidine has an effective role in inhibiting bacterial plaque. Since chlorhexidine adheres very firmly to dental tissue and maintains its effect for hours, it is a very effective antibacterial drug. For this reason (reduction of oral bacteria), chlorhexidine is an effective drug to reduce or eliminate bad breath; Thus, in addition to reducing bacteria, chlorhexidine reduces the sulfur created by anaerobic bacteria.

This substance is prescribed as a 0.12% mouthwash for high-risk patients and for a short period of time. Chlorhexidine, which is used to protect teeth against decay, can also be in the form of varnish. The best and most effective type of varnish is the one applied by the dentist on the teeth. Chlorhexidine causes remineralization of primary caries lesions and by reducing the amount of mutans streptococci, it reduces the rate of caries growth. If chlorhexidine is used for about 2 weeks; Mutans streptococci remain below the caries-causing level for 12-26 weeks. It is recommended to use chlorhexidine continuously for 2 weeks in people with high caries risk or people with acute caries. After completing the treatment period in these people, weekly use is enough to keep mutans streptococci down. Using chlorhexidine mouthwash does not make the patient unnecessary to use toothbrush and dental floss.

● Spectrum of effect: Chlorhexidine is active against a range of aerobic and anaerobic, Gram-positive and Gram-negative bacteria. This drug is also effective against chlamydia trachomatis, some fungi and some viruses, but it has no effect on mycobacteria. Chlorhexidine is effective against a wide range of aerobic gram-positive bacteria, including Streptococcus mutans pyogenes (group A beta-hemolytic streptococci), Streptococcus salivarius, and Streptococcus sanguis. Chlorhexidine also has an effect on Staphylococcus aureus, Streptococcus epidermidis, Streptococcus hemolyticus, Streptococcus hominis, and Streptococcus simulans.

Although some groups of Escherichia coli, Klebsiella, Salmonella and Pseudomonas are inactivated by chlorhexidine in vitro; But in vivo, a large group of these gram-negative bacteria respond to higher concentrations of chlorhexidine and are therefore practically resistant to this drug.

Anaerobic bacteria: Chlorhexidine is effective in vitro against some groups of Bacteroides, Clostridium difficile, and Selenomonas, but it has less effect on Vilonella. Subgingival tablets are effective against some pus-causing bacteria such as Porphyromonas gingivalis, Provetella intermedia, Forsytus, and Campylobacter rectus.

Fungi: In in vitro tests, chlorhexidine is effective against Candida albicans, Candida doublinensis, Candida glabrata, Candida Guillermondi, Candida kefir, Candida crusi, Candida leucine, and Candida tropicalis.

Viruses: It seems that chlorhexidine is effective against viruses that have lipid compounds in their outer coat or have an outer envelope. Although its clinical significance is unclear, there is evidence that chlorhexidine has in vitro activity against cytomegalovirus (CMV), human immunodeficiency virus (HIV), herpes simplex types 1 and 2 (HSV-1 and HSV-2). , influenza virus, parainfluenza virus, and variola virus are effective.

Resistance to chlorhexidine: apart from bacterial spores and some gram-negative bacteria that are naturally resistant to chlorhexidine, the development of acquired resistance to this drug in microorganisms that were sensitive to it has rarely been reported.

● The use of chlorhexidine in periodontal diseases:

Chlorhexidine gluconate 0.12 topical solution is used as a mouthwash in the treatment of gingivitis. This mouthwash reduces the prevalence and severity of mucosal inflammation (mucositis) and other complications of immunosuppressive diseases and reduces the prevalence of hospital infections of the respiratory system. Chlorhexidine gluconate is used under the gums in the form of absorbable tablets as an adjunctive treatment for patients with periodontitis.

Gingivitis: 0.12 chlorhexidine gluconate topical solution is used in the treatment of gingivitis in adults. This topical oral solution is used between dental appointments as a professional application in the treatment of gingivitis. Also, chlorhexidine topical solution has been used as an adjunctive treatment in the treatment of acute necrotizing ulcerative gingivitis. The safety and effectiveness of chlorhexidine oral solution for this purpose has not yet been determined.

The logic of using chlorhexidine gluconate topical solution in the treatment of gingivitis is based on both the antibacterial effects of this drug and its anti-plaque effects. The remaining antimicrobial properties reported along with chlorhexidine have made it the drug of choice for plaque control and gingivitis treatment. The result of a study on adults without symptoms of periodontitis has shown that a single use of 0.2% chlorhexidine mouthwash reduces the number of bacteria in saliva for at least 7 hours and is more effective than other mouthwashes (for example, compared to: steel pyridinium chloride, phenolic rugenha, triclosan, zinc chloride).

In another study in adults without symptoms of periodontitis, 0.2% chlorhexidine mouthwash reduced the amount of dentogingival plaque more than other tested mouthwashes such as phenolic oils. Microbiological sampling of dental plaque after 6 months of using chlorhexidine gluconate topical solution has shown a 54-97% reduction in the number of some anaerobic bacteria.

The results of a large number of controlled studies in adults with gingivitis show that the use of 0.12% chlorhexidine oral solution twice a day for 6 weeks as a mouthwash reduces gingivitis, gum bleeding, and plaque compared to Placebo or mouthwashes containing other substances (such as phenolic oils, sanguinarine).

Dosage of chlorhexidine in gingivitis: The usual dose for adults is 0.12% chlorhexidine gluconate topical solution for use as a mouthwash, 15 ml twice a day for 30 seconds (morning and night after brushing).

Periodontitis: Chlorhexidine gluconate can be used under the gums in the form of absorbable tablets containing chlorhexidine as an adjunctive treatment along with scaling and root planning to reduce pocket depth in the treatment of adult periodontitis. Chlorhexidine gluconate is used subgingivally as part of maintenance periodontitis treatments that include good oral hygiene after removal of bacterial plaque by the dentist. The safety and usefulness of using chlorhexidine gluconate under the gums in periodontal pockets with abscesses has not been proven so far and is not recommended.

Among the used mouthwashes, chlorhexidine has been studied more than others and has been introduced as the gold standard.

In cases where brushing is not possible temporarily, chlorhexidine mouthwash can be used as a substitute for brushing; For example, when it is not possible to use a toothbrush after oral surgery or gum surgery due to the presence of wounds and stitches, the use of chlorhexidine is very effective. In this situation, the healing of wounds and oral injuries is accelerated by chemical control of microbial plaque; Or when two jaws are fixed to each other to treat jaw fractures and the person is unable to open the mouth and use a toothbrush. Of course, it should be remembered that normally mouthwash cannot be used as a substitute for a toothbrush in controlling microbial plaque and cleaning dental surfaces, but it is better to use mouthwash along with brushing and to complete it.

● Side effects of using chlorhexidine mouthwash

Usually, the side effects associated with chlorhexidine are mild and usually do not need to stop the treatment. The most common reported side effect of chlorhexidine mouthwash; Staining of the teeth, cosmetic restorations, the back surface of the tongue and other oral surfaces and increasing the formation of mass and change in the sense of taste.

As mentioned, chlorhexidine causes a brown color to appear on the teeth and fillings of the same color as the teeth, oral mucosa and tongue. This is attributed to the binding of cationic groups of chlorhexidine to substances in the diet such as gallic acid and tannins, and its intensity depends on the amount of substance consumed and the time of its consumption. This discoloration is external and can be removed by tooth polishing. Another side effect of chlorhexidine, which is not very common, is mucosal injuries depending on the concentration of chlorhexidine.

Chlorhexidine has an unpleasant taste and can cause temporary changes in the sense of taste. Especially, this effect is related to the taste of salt, which makes the food tasteless, and this change depends on the concentration of chlorhexidine. The sense of taste that is most affected; Sweetness, followed by saltiness and sourness, and finally bitterness. Usually these changes are temporary. The reason for this change is the denaturation of the surface proteins located on the taste buds.

A few cases of unilateral or bilateral swelling of the parotid gland due to chlorhexidine consumption have been reported. By inhibiting the breakdown of glucose by bacteria, chlorhexidine prevents acid production and keeps the environment alkaline; This factor prepares the ground for the formation of supragingival masses.

Drug interactions: Chlorhexidine is incompatible with soaps and anionic cleaners.

Warnings: contact of the drug with eyes, middle ear and body cavities should be avoided.

Side effects: Irritation, dermatitis, or sensitivity to light may occur with chlorhexidine. Chlorhexidine 0.12% mouthwash, in addition to destroying some pathogenic streptococci, also destroys some of the natural microflora of the mouth, which is one of the undesirable features of this mouthwash.

Carcinogenicity: No mutagenic properties were observed in this drug in two in vivo studies on mammals. In several other studies, it was shown that chlorhexidine does not have genotoxic properties. The level of mutagenicity of mouthwashes available in the market has not been investigated so far.

Pregnancy: Studies on rats and rabbits have shown that chlorhexidine does not have adverse effects on the fetus.

Breastfeeding: The possibility of the drug entering breast milk has not yet been determined, and therefore subgingival tablets should be prescribed to breastfeeding mothers only when needed.

Recommended points:

۱- One should refrain from taking medicine.

۲- In case of irritation, dermatitis or sensitivity to light, the use of the drug should be stopped.

● Summary and conclusion
Due to the limited side effects and the absence of toxic and systemic side effects and due to the significant antimicrobial effects of this mouthwash, today, the combination of chlorhexidine gluconate is widely used as a mouthwash and its use in short-term periods and especially at the same time as scaling And oral surgeries are increasingly recommended.

Dr. Sahar Mirzabigi – dentist