CHLORHEXIDINE

INTRODUCTION
They are antiplaque agents . secondary to disease or disability may benefit from antiplaque agents such as chlorhexidine and Listerine or its generic counterparts. Chlorhexidine is a cationic bisbiguanide that has been used as a broad-spectrum antiseptic in medicine since the 1950s. In Europe, a 0.2% concentration of chlorhexidine has been used for years as a preventive and therapeutic agent.

 Chlorhexidine binding to oral structures results in substantivity. It is either bacteriostatic or bactericidal depending on the dose. Some adverse effects of chlorhexidine include an increase in calculus formation, staining of teeth, dysgeusia (altered taste), and permanent staining of teeth. Chlorhexidine is a prescription rinse for shortterm use (<6 months); longterm use (>6 months) has not been extensively studied.

 The American Dental Association (ADA) Council on Dental Therapeutics has approved chlorhexidine to help prevent and reduce supragingival plaque and gingivitis. Although chlorhexidine has not been studied in older adults, outcomes in younger persons, including those with disabilities, suggest that it is also effective in older adults. Chlorhexidine may be particularly useful for older adults who have difficulty with plaque removal and those who take phenytoin, calcium channel blockers, and cyclosporins and are at risk for gingival hyperplasia.

HISRORY
Chlorhexidine was developed in the 1940s by Imperial Chemical Industries, England, and marketed in 1954 as an antiseptic for skin wounds. Later, the antiseptic was more widely used in medicine and surgery including obstetrics, gynecology, urology and presurgical skin preparation for both patient and surgeon. Use in dentistry was initially for presurgical disinfection of the mouth and in endodonticsendodontics. Plaque inhibition by chlorhexidine was first

 Investigated in 1969 (Schroeder 1969), but the definitive study was performed by Loe and Schiott (1970). This study showed that rinsing for 60 seconds twice per day with 10 ml of a 0.2% (20 mg dose) chlorhexidine gluconate solution in the absence of normal tooth cleaning, inhibited plaque regrowth and the development of gingivitis. Numerous studies followed, such that chlorhexidine was one of the most investigated compounds in dentistry (for review see Jones 1997). Chlorhexidine is a bisbiguanide antiseptic, being a symmetrical molecule consisting of four chlorophenyl rings and two biguanide groups connected by a central hexamethylene bridge (Fig.1). The compound is a strong base and dicationic at pH levels above 3.5, with two positive charges on either side of a hexamethylene bridge (Albert & Sargeant 1962). Indeed, it is the dicationic nature of chlorhexidine, making it extremely interactive with anions, which is relevant to its efficacy, safety, local side effects and difficulties with formulation in products.

Fig. 1 Chlorhexidine molecule.

TOXICITY
The cationic nature of chlorhexidine minimizes absorption through the skin and mucosa, including from the gastrointestinal tract. Hence the toxicity is therefore not reported.

SIDE EFFECTS
1. Brown discoloration of the teeth and some restorative materials and the dorsum of the tongue (to be discussed further) (Figs. 2 and 3). 2. Taste perturbation where the salt taste appears to be preferentially affected (Lang et al. 1988) to leave food and drinks with a rather bland taste. 3. Oral mucosal erosion (Fig. 22-5). This appears to be an idiosyncratic reaction and concentration dependent. Dilution of the 0.2% formulation to 0.1%, but rinsing with the whole volume to maintain dose, usually alleviates the problem. Erosions are rarely seen with 0.12% rinse products used at 15 ml volume.

Unilateral or bilateral parotid swelling (Fig.4). This is an extremely rare occurrence and an explanation is not available. 5. Enhanced supragingival calculus formation. This effect may be due to the precipitation of salivary proteins on to the tooth surface, thereby increasing pellicle thickness and/or precipitation of inorganic salts on to the pellicle layer. Certainly pellicle forming under the influence of chlorhexidine shows an early and highly calcified structure (Leach 1977). Chlorhexidine also has a bitter taste, which is difficult to mask completely.

Mechanism of action
Chlorhexidine is a potent antibacterial substance but this alone does not explain its antiplaque action. The antiseptic binds strongly to bacterial cell membranes. Consistent with the original work and conclusions (Davies et al. 1970), a more recent study and review suggested that plaque inhibition is derived only from the chlorhexidine adsorbed to the tooth surface (Jenkins et al. 1988). It is possible that the molecule attaches to pellicle by one cation leaving the other free to interact with bacteria attempting to colonize the tooth surface.

FORMS
Mouthrinses:- Aqueous alcohol solutions of 0.2% chlorhexidine were first made available for mouthrinse products for twice daily use in Europe in the 1970s. A 0.1% mouthrinse product also became available; however questions were raised over the activity of the 0.1% product and in some countries the efficacy of this product is less than would be expected from a 0.1% solution (Jenkins et al. 1989). Later, in the US, a 0.12% mouthrinse was manufactured but to maintain the almost optimum 20 mg doses derived from 10 ml of 0.2% rinses, the product was recommended as a 15 ml rinse (18 mg dose). The studies revealed equal efficacy for 0.2% and 0.12% rinses when used at appropriate similar doses ( Segreto et al. 1986).

 Gel:- A 1% chlorhexidine gel product is available and can be delivered on a toothbrush or in trays. The distribution of the gel by toothbrush around the mouth appears to be poor and preparations must be delivered to all tooth surfaces to be effective (Saxen et al. 1976). More recently, 0.2% and 0.12% chlorhexidine gels have become available. Sprays:- 0.1% and 0.2% chlorhexidine in sprays are commercially available in some countries. Studies with the 0. 2% spray have revealed that small doses of approximately 1-2 mg delivered to all tooth surfaces produces similar plaque inhibition to a rinse with 0.2% mouthrinses (Kalaga et al. 1989a). Sprays appear particularly useful for the physically and mentally handicapped groups, being well received by individuals and their carers (Francis et al 1987a,b, Kalaga et al. 1989b).

 Toothpaste:- Chlorhexidine is difficult to formulate into toothpaste for reasons already given and early studies produced variable outcomes for benefits to plaque and gingivitis ( Gjermo & Rolla 1970, 1971, Johansen et al. 1972,1975). More recently, a 1% chlorhexidine toothpaste with and without fluoride was found to be superior to the control product for the prevention of plaque and gingivitis in a 6-month home use study (Yates et al. 1993). However, stain scores were markedly increased as was supragingival calculus formation, and the manufacturer did not produce a commercial product. For a short time a commercial product was available, having been shown to be efficacious for both plaque and gingivitis (Sanz et al. 1994). Although effective, chlorhexidine products based on toothpaste and sprays produce similar tooth staining to mouthrinses and gels; taste disturbance, mucosal erosion and parotid swellings tend to be less or have never been reported.

 Chewing gum:- the vehicle has been used to deliver chemical agents such as chlorhexidine and, when used as an adjunct to normal toothbrushing, reduced plaque and gingivitis levels have been shown (Ainamo & Etemadzadeh 1987, Ainamo et al. 1990, Smith et al. 1996). Varnishes:- Varnishes have been employed to deliver antiseptics including chlorhexidine, but the purpose has been to prevent root caries rather than as a reservoir for plaque control throughout the mouth.

THE CHLORHEXIDINE CHIP

The chlorhexidine chip, PerioChip. Is manufactured by Perio Products Ltd,, Jerusalem, Israel and is currently beittg studied in the US under the sponsorship of Astra USA. Inc, It is available in Israel and the UK and has recently been cleared for use in the US and in a number of European countries. The chlorhexidine chip is an orange-brown rectangular chip rounded on 1 end. It measures 4 mm by 5 mm by 0,35 mm. It weighs 7,4 mg and contains 2,5 mg of chlorhexidine gluconate in a gelatin matrix.

The chip is biodegradable and indicated for use in periodontal pockets that are 5 mm or more. The chip, which is very user friendly, is inserted into the pocket by means of a cotton forceps. By grasping the flat end of the chip the clinician can place the rounded end into the periodonta pocket. It is recommended that the area to be treated be dry since a wet chip may become soft and more difficult to insert. The entire procedure takes less than 1 min. No retention system is required. The patient should refrain from dossing for 10 days to avoid dislodging the chip. The chip bio-degrades in 710 days and does not require an additional appointment for removal.

CONCLUSION
Chlorhexidine is thus far the most studied and effective antiseptic for plaque inhibition and the prevention of gingivitis. Consequent upon the original publication (Loe & Schiott 1970), chlorhexidine, arguably perhaps, represents the nearest that research has come to identifying a chemical agent that could be used as a replacement for, rather than an adjunct to, mechanical oral hygiene practices. Other bisbiguanides such as alexidine and octenidine have less or similar activity, respectively, to chlorhexidine but bring with them no improvement in local side effects and have less toxicity data available. Chlorhexidine has thus remained the only bisbiguanide used in a number of vehicles and available in commercial products. In view of the importance of this antiseptic within preventive dentistry, a separate section later in the chapter will be devoted to considering its activity and usage in the mouth.

REFERENCES

 Killoy WJ et al. The use of locally-delivered chlorhexidine in the treatment of periodontitis. Clinical results. J Clin Periodontol 1998: 25: 953-958.