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Chlorhexidine Gluconate

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Chlorhexidine Gluconate

Chlorhexidine is an antiseptic, first discovered and developed by Imperial Chemical Industries (ICI) and introduced under the brand name Hibitane.[1][2] ICI also discovered and developed another antiseptic cetrimide and introduced Savlon which was a combination of both cetrimide and chlorhexidine. Chlorhexidine is effective on both Gram-positive and Gram-negative bacteria, although it is less effective with some Gram-negative bacteria.[3] It has both bactericidal and bacteriostatic mechanisms of action, the mechanism of action being membrane disruption, not ATPase inactivation as previously thought.[4][5] It is also useful against fungi and enveloped viruses, though this has not been extensively investigated.

Safety

Chlorhexidine is harmful in high concentrations, but is used safely in low concentrations in many products, such as mouthwash and contact lens solutions. However, numerous scientific papers have reported complications with low level exposure as well.[6][7][8]

In the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) has issued a patient safety alert on the risk of MHRA alert. Further guidance on anaphylaxis is available from NICE, the Resuscitation Council and The Association of Anaesthetists of Great Britain and Ireland (AAGBI).

Dental use

Chlorhexidine is often used as an active ingredient in mouthwash designed to reduce dental plaque and oral bacteria. It has been shown to have an immediate bactericidal action and a prolonged bacteriostatic action due to adsorption onto the pellicle-coated enamel surface.[9] If it is not deactivated, chlorhexidine lasts longer in the mouth than other mouthwashes and this is partly why it is to be preferred over other treatments for gingivitis.[10] To treat periodontal pockets equal or greater 5mm chlorhexidine is also available in high concentration (36%) in a gelatine-chip (PerioChip).

There are oral pathologic conditions in which the maintenance of oral hygiene with the twice-daily use with 0.12% chlorhexidine-gluconate solution (in which a salt of chlorhexidine and gluconic acid has been dissolved) is required for healing and regeneration of the oral tissues. These conditions included gingivitis, periodontitis, dental traumas[11] (such as subluxation), oral cysts,[12] and after wisdom tooth extraction. The clinical efficacy of the application of chlorhexidine as a component of oral rinses is well documented by many clinical studies that are summarized by review articles.[13]

Continued use of products containing chlorhexidine for long periods can cause stains on teeth, tongue, and gingiva, also on silicate and resin restorations; prolonged use can also reduce bitter and salty taste sensations - this latter symptom can be reversed by ceasing use of chlorhexidine.[14] The brownish discoloration of teeth and tongue are due to the fact that the disintegration of bacterial membranes leads to the denaturation of bacterial proteins.[15] At the same time, disulfide functions are reduced to thiol functions[16] that form dark complexes with iron(III) ions found in saliva.[17] Other discolorations might be caused by monosaccharides such as glucose and fructose that are dissolved in saliva and that react with the amine functions of bacterial proteins[15] (Maillard reaction).

A version which stains the teeth less has been developed.[18] The assumption that the extent of discolorations is directly proportional to the efficacy of products containing chlorhexidine[19][20][21] is doubtful, due to several reasons. As long as chlorhexidine is incorporated into the bacterial membrane and its substantivity is not impaired, the efficacy of these products should not be affected. Indeed, efforts to prevent the formation of brownish deposits by the addition of reducing agents such as ascorbic acid that react with iron(III) ions, and of nucleophiles such as sulfite ions that react with glucose and fructose, have been successful.[22] Clinical studies with patients suffering from periodontitis show that the post-operative treatment with an ethanol-free mouthrinse containing chlorhexidine (0,2%) for seven days is not negatively affected by addition of ascorbic acid and sulfite (anti discoloration system ADS®) while the extent of the discolorations observed is lowered significantly. However, a clinical study with healthy volunteers[23] that examined not gingival health but several plaque parameters indicates superiority of a conventional formulation. This apparent superiority is attributed to the ethanol contained in the conventional solution. Moreover, it is assumed that ascorbic acid and sulfite in the ethanol-free mouth rinse prevent the adsorption of the chlorhexidine by teeth and gingiva resulting in a lower substantivity. However, there is no plausible mechanism for such an impairment. The neutral ascorbic acid or the negatively charged ascorbate or the negatively charged sulfite should not affect the attachment of the two-fold positively charged chlorhexidine to teeth and gingiva. Also, a combination of negatively charged sulfite or ascorbate and positively charged chlorhexidine leading to a precipitate of chlorhexidine-sulfite or chlorhexidine-ascorbate does not take place as this would lead to a complete inactivation of the mouth rinse that was never observed. Therefore, it can be concluded that the substantivity of chlorhexidine remains unaffected by the addition of sulfite and ascorbic acid. The apparent inconsistency of the gingival health study[22] with the plaque-regrowth study[23] might be due to differences in the choice of study parameters. While plaque seems to be a required prerequisite for gingival inflammation (gingivitis), a plaque-regrowth study with healthy volunteers, strictly speaking, does not allow conclusions regarding the efficacy of a mouth rinse on the gingival health of patients suffering from periodontitis. However, the gingival health study should be decisive for the dentist in the field.

According to Colgate,[24][unreliable source?] chlorhexidine gluconate has not been proven to reduce subgingival calculus and in some studies actually increased deposits. When combined with xylitol, a synergistic effect has been observed to enhance efficacy.[25]

Chlorhexidine's role in preventing tooth decay (dental caries) is controversial. In a 2008 article for Operative Dentistry, dentistry researcher Jaana Autio-Gold has written:

Based on the available reviews, chlorhexidine rinses have not been highly effective in preventing caries, or at least the clinical data are not convincing. Due to the current lack of long-term clinical evidence for caries prevention and reported side effects, chlorhexidine rinses should not be recommended for caries prevention. Due to the inconclusive literature and sparse clinical data on gels and varnishes, their use for caries prevention should also be studied further to develop evidence-based recommendations for their clinical role in caries prevention. Since dental caries is a disease with a multifactoral etiology, it is currently more appropriate to use other established, evidence-based prevention methods, such as fluoride applications, diet modifications and good oral hygiene practices. Recent findings also indicate that the effect of an antimicrobial agent for reducing the levels of mutans streptococci or plaque reduction may not always correlate with eventual caries reduction.[26]

Chlorhexidine is neutralized by common toothpaste additives such as sodium lauryl sulfate (SLS) and sodium monofluorophosphate (MFP). Although data are limited, to maximize effectiveness it may be best to keep a 30-minute to 2-hour interval between brushing and using the mouthwash.[27]

In order to increase efficacy and stability, despite possible health risks such as cancer,[28][29][30] mouth rinses with chlorhexidine often contain 6-7% ethanol[23] as a preservative; however, ethanol-free chlorhexidine mouthwashes are available in Europe.[31]

Topical

Chlorhexidine is used as a topical antiseptic skin scrub in hospital and household settings. It is used for general skin cleansing, as a surgical scrub, and as a pre-operative skin preparation. It is often used as a rubbing agent prior to the use of hypodermic or intravenous needles in place of iodine. Chlorhexidine is contraindicated for use near the meninges, in body cavities, and near the eyes and ears. At the 2% concentration, it can cause serious and permanent injury with prolonged contact with the eye or if instilled carefully and going through the nose through a perforated eardrum. Nevertheless, a topical solution of 0.02% chlorhexidine is recommended by the US Centers for Disease Control and Prevention (CDC) as treatment for keratitis caused by Acanthamoeba. As a scrub, chlorhexidine is not recommended on persons under two months of age. Anionic ingredients in many leave-on topicals and cosmetics, including those in acne products, cleansers, and moisturizers, will inactivate it.

Use in animals

For use in animals, it is used as a topical disinfectant of wounds. Some common brand names are ChlorhexiDerm, ResiChlor, Savinox plus (Bioshields), Germi-STAT Antimicrobial Skin Cleanser, Nolvasan Skin and Wound Cleaner, and Nolvasan Ointment. It is also more beneficial to wound healing than using saline solutions alone.[32] Problems[33] including deafness[34] have been associated with the use of chlorhexidine products in cats. It is commonly used to manage skin infections in dogs. In addition to this it is an active ingredient in teat disinfectant products used within the dairy farming industry.

Deactivation

Chlorhexidine is deactivated by anionic compounds, including the anionic surfactants commonly used as detergents in toothpastes and mouthwashes, anionic thickeners such as carbomer, and anionic emulsifiers such as acrylates/C10-30 alkyl acrylate crosspolymer, among many others. For this reason, chlorhexidine mouth rinses should be used at least 30 minutes after other dental products.[35] For best effectiveness, food, drink, smoking, and mouth rinses should be avoided for at least one hour after use. Many topical skin products, cleansers, and hand sanitizers should also be avoided to prevent deactivation when chlorhexidine (a topical itself or the residue from a cleanser) is meant to remain on the skin.

The rival chemical PCMX does not have this issue or the warnings about eye & middle-ear contact, though it is usually less potent in the form and concentrations normally used.

Although chlorhexidine is effective in the presence of blood, real soap, and pus, its activity is reduced.[3]

References

External links

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