Chlorhexidine
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| Systematic (IUPAC) name | |
| N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)] | |
| Clinical data | |
| Trade names | Hibiclens |
| AHFS/Drugs.com | FDA Professional Drug Information |
| Pregnancy cat. | ? |
| Legal status | ? |
| Identifiers | |
| CAS number | 55-56-1  |
| ATC code | A01AB03 B05CA02, D08AC02, D09AA12 (dressing), R02AA05, S01AX09, S02AA09, S03AA04 |
| PubChem | CID 5353524 |
| DrugBank | DB00878 |
| ChemSpider | 2612 |
| UNII | R4KO0DY52L |
| KEGG | D07668 |
| ChEBI | CHEBI:3614 |
| ChEMBL | CHEMBL790 |
| Chemical data | |
| Formula | C22H30Cl2N10 |
| Mol. mass | 505.446 g/mol |
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Chlorhexidine is a chemical antiseptic.[1] It is effective on both Gram-positive and Gram-negative bacteria, although it is less effective with some Gram-negative bacteria.[2] It has both bactericidal and bacteriostatic mechanisms of action, the mechanism of action being membrane disruption, not ATPase inactivation as previously thought.[3] It is also useful against fungi and enveloped viruses, though this has not been extensively investigated.[citation needed]
Contents |
Safety [edit]
Chlorhexidine is harmful in high concentrations, but is used safely in low concentrations in many products, such as mouthwash and contact lens solutions.[citation needed] However, numerous scientific papers have reported complications with low level exposure too.[4][5][6]
In the UK, the Medicines and Healthcare Products Regulatory Agency (MHRA) has issued a patient safety alert on the risk of anaphylactic reactions from the use of medical devices and medicinal products containing chlorhexidine. Further details can also be found in the MHRA alert. Further guidance on anaphylaxis is available from NICE, the Resuscitation Council and The Association of Anaesthetists of Great Britain and Ireland (AAGBI).
Availability [edit]
Chlorhexidine is present in oral rinses and skin cleansers, and in small quantities it is used as a preservative.
As a component of mouth-rinses, chlorhexidine is sometimes marketed under the brand names Foam Safe, Hexicleans, Peridex, Perichlor or Periogard Oral Rinse. Chlorhexidine digluconate is also available as a chlorhexidine-chip (PerioChip) in the UK, USA and in Germany, Austria, The Netherlands, Italy. In the UK CHX-rinse products are mainly marketed under the brand name Corsodyl (or Chlorohex); in Italy, Germany, Switzerland and other European countries as ethanol-free Curasept ADS; in Spain as Cristalmina; in Germany as Chlorhexamed; in Australia and New Zealand as Savacol; in Greece as Chlorhexil (Intermed S.A.); in India as Suthol (G. D. Pharmaceuticals), Sterimax (Bioshields), Clohex or Dejavu-MW (QUADRA); in Venezuela as Perioxidina or Peridont, in Japan as Oronine and in some Central American countries as Clorexil.In Slovenia and Serbia it is known as Hibitan.
As a skin cleanser, it is marketed under brand names such as Hibiclens, Savinox plus (Bioshields), Surgiprep-CHX (Bioshields), Hibiscrub, or Dexidin mainly as a surgical scrub, Hexigard 4 as surgical hand wash, Hexigard HR as hand rub (Mil Laboratories Pvt Ltd). It is also used in some acne skin washes. It is also used as part of a treatment for athlete's foot. In some countries, it is available by prescription only. In the United States, it used to only be available by prescription, but is now available over-the-counter.
For wounds/lacerations, it is available in the United States by prescription as a wound debridement and cleansing system under the brand name Irrisept.
Together with benzalkonium chloride it is one of the active ingredients in Dermol, an emollient medicine that helps treat and prevent dry, rough, and itchy skin associated with conditions such as dermatitis and eczema.
Dental use [edit]
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.[7] 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.[8] 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[9] (such as subluxation), oral cysts,[10] 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.[11]
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 alter taste sensation - this latter symptom can be reversed by ceasing use of chlorhexidine.[12] 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.[13] At the same time, disulfide functions are reduced to thiol functions[14] that form dark complexes with iron(III) ions found in saliva.[15] 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[13] (Maillard reaction).
A version which stains the teeth less has been developed.[16] The assumption that the extent of discolorations is directly proportional to the efficacy of products containing chlorhexidine[17][18][19] 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.[20] 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[21] 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[20] with the plaque-regrowth study[21] 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,[22][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.[23]
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.[24]
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.[25]
In order to increase efficacy and stability, despite possible health risks such as cancer,[26][27][28] mouth rinses with chlorhexidine often contain 6-7% ethanol[21] as a preservative; however, ethanol-free chlorhexidine mouthwashes are available in Europe.[29]
Topical [edit]
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[clarification needed]. 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 [edit]
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.[30] Problems[31] including deafness[32] 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 [edit]
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.[33] 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.[citation needed]
Although chlorhexidine is effective in the presence of blood, real soap, and pus, its activity is reduced.[2]
References [edit]
- ^ "Chlorhexidine". Drugs.com. August 2011. Retrieved 2011-09-11.
- ^ a b World Health Organization, Department of Reproductive Health and Research (1998). "The most common topical antimicrobial". Care of the Umbilical Cord. World Health Organization. Retrieved 2010-09-11.
- ^ Ray, Ava; Redhead, Keith; Selkirk, Susanna; Poole, Stephen (1991). "Variability in LPS composition, antigenicity and reactogenicity of phase variants of Bordetella pertussis". FEMS Microbiology Letters 79 (2–3): 211–7. doi:10.1111/j.1574-6968.1991.tb04531.x. PMID 2060761.
- ^ Sivathasan, Niroshan; Ramamurthy, Nitin Kumar; Pabla, Ravinder Singh (2010). "Chemical Burns Associated with Chlorhexidine-Alcohol Solution: An Avoidable Complication?". Journal of Burn Care & Research 31 (5): 833. doi:10.1097/BCR.0b013e3181eed4d6. PMID 20644490.
- ^ Sivathasan, N; Sivathasan, N; Vijayarajan, L (2010). "Chlorhexidine's complications". Journal of perioperative practice 20 (8): 300–1. PMID 20860191.
- ^ Sivathasan, N.; Goodfellow, P. B. (2011). "Skin Cleansers: The Risks of Chlorhexidine". The Journal of Clinical Pharmacology 51 (5): 785–6. doi:10.1177/0091270010372628. PMID 21383335.
- ^ Jenkins, S.; Addy, M.; Wade, W. (1988). "The mechanism of action of chlorhexidine. A study of plaque growth on enamel inserts in vivo". Journal of Clinical Periodontology 15 (7): 415–24. doi:10.1111/j.1600-051X.1988.tb01595.x. PMID 3183067.
- ^ Gaffar, A; Afflitto, J; Nabi, N (1997). "Chemical agents for the control of plaque and plaque microflora: An overview". European journal of oral sciences 105 (5 Pt 2): 502–7. PMID 9395116.
- ^ Zadik, Yehuda (2008). "Algorithm of first-aid management of dental trauma for medics and corpsmen". Dental Traumatology 24 (6): 698–701. doi:10.1111/j.1600-9657.2008.00649.x. PMID 19021668.
- ^ Zadik, Yehuda; Yitschaky, Oded; Neuman, Tzahi; Nitzan, Dorrit W. (2011). "On the Self-Resolution Nature of the Buccal Bifurcation Cyst". Journal of Oral and Maxillofacial Surgery 69 (7): e282–4. doi:10.1016/j.joms.2011.02.124. PMID 21571416.
- ^ Lang, Niklausp.; Brecx, Michel C. (1986). "Chlorhexidine digluconate-an agent for chemical plaque control and prevention of gingival inflammation". Journal of Periodontal Research 21: 74–89. doi:10.1111/j.1600-0765.1986.tb01517.x.
- ^ Helms, Jill A.; Della-Fera, Mary Anne; Mott, April E.; Frank, Marion E. (1995). "Effects of chlorhexidine on human taste perception". Archives of Oral Biology 40 (10): 913–20. doi:10.1016/0003-9969(95)00062-T. PMID 8526801.
- ^ a b Hjeljord, LG; Rolla, G; Bonesvoll, P (1973). "Chlorhexidine-protein interactions". Journal of periodontal research. Supplement 12: 11–6. doi:10.1111/j.1600-0765.1973.tb02158.x. PMID 4269593.
- ^ Gilbert, Hiram F. (2006). "Molecular and Cellular Aspects of Thiol-Disulfide Exchange". Advances in Enzymology and Related Areas of Molecular Biology. pp. 69–172. doi:10.1002/9780470123096.ch2. ISBN 978-0-470-12309-6.
- ^ Jocelyn, PC (1972). Biochemistry of the SH Group. London-New York: Academic Press. p. 82. ISBN 0-12-385350-8.
- ^ Bernardi, F; Pincelli, MR; Carloni, S; Gatto, MR; Montebugnoli, L (2004). "Chlorhexidine with an Anti Discoloration System. A comparative study". International Journal of Dental Hygiene 2 (3): 122–6. doi:10.1111/j.1601-5037.2004.00083.x. PMID 16451475.
- ^ Addy, M; Roberts, WR (1981). "Comparison of the bisbiguanide antiseptics alexidine and chlorhexidine. II. Clinical and in vitro staining properties". Journal of clinical periodontology 8 (3): 220–30. PMID 6947988.
- ^ Addy, M; Wade, WG; Jenkins, S; Goodfield, S (1989). "Comparison of two commercially available chlorhexidine mouthrinses: I. Staining and antimicrobial effects in vitro". Clinical preventive dentistry 11 (5): 10–4. PMID 2638949.
- ^ Jenkins, S; Addy, M; Newcombe, R (1989). "Comparison of two commercially available chlorhexidine mouthrinses: II. Effects on plaque reformation, gingivitis, and tooth staining". Clinical preventive dentistry 11 (6): 12–6. PMID 2638954.
- ^ a b Cortellini, Pierpaolo; Labriola, Antonella; Zambelli, Raffaella; Pini Prato, Giovanpaolo; Nieri, Michele; Tonetti, Maurizio S. (2008). "Chlorhexidine with an anti discoloration system after periodontal flap surgery: A cross-over, randomized, triple-blind clinical trial". Journal of Clinical Periodontology 35 (7): 614–20. doi:10.1111/j.1600-051X.2008.01238.x. PMID 18422695.
- ^ a b c Arweiler, Nicole B.; Boehnke, Nils; Sculean, Anton; Hellwig, Elmar; Auschill, Thorsten M. (2006). "Differences in efficacy of two commercial 0.2% chlorhexidine mouthrinse solutions: A 4-day plaque re-growth study". Journal of Clinical Periodontology 33 (5): 334–9. doi:10.1111/j.1600-051X.2006.00917.x. PMID 16634954.
- ^ "Colgate Periogard Rinse (Rx only)". Colgate. Retrieved 2011-09-12.
- ^ Decker, EM; Maier, G; Axmann, D; Brecx, M; Von Ohle, C (2008). "Effect of xylitol/chlorhexidine versus xylitol or chlorhexidine as single rinses on initial biofilm formation of cariogenic streptococci". Quintessence international 39 (1): 17–22. PMID 18551212.
- ^ Autio-Gold, J (2008). "The role of chlorhexidine in caries prevention". Operative dentistry 33 (6): 710–6. doi:10.2341/08-3. PMID 19051866.
- ^ Kolahi, J; Soolari, A (2006). "Rinsing with chlorhexidine gluconate solution after brushing and flossing teeth: A systematic review of effectiveness". Quintessence international 37 (8): 605–12. PMID 16922019.
- ^ Elmore, J; Horwitz, R (1995). "Oral cancer and mouthwash use: Evaluation of the epidemiologic evidence". Otolaryngology - Head and Neck Surgery 113 (3): 253–61. doi:10.1016/S0194-5998(95)70114-1. PMID 7675486.
- ^ Winn, Deborah M.; Blot, William J.; McLaughlin, Joseph K.; Austin, Donald F.; Greenberg, Raymond S.; Preston-Martin, Susan; Schoenberg, Janet B.; Fraumeni Jr, Joseph F. (1991). "Mouthwash Use and Oral Conditions in the Risk of Oral and Pharyngeal Cancer". Cancer Research 51 (11): 3044–7. PMID 2032242.
- ^ Llewelyn, J (1994). "Oral squamous cell carcinoma. Mouthwashes may increase risk". BMJ 308 (6942): 1508. PMC 2540286. PMID 8019293.
- ^ Bernardi, F; Pincelli, MR; Carloni, S; Gatto, MR; Montebugnoli, L (2004). "Chlorhexidine with an Anti Discoloration System. A comparative study". International journal of dental hygiene 2 (3): 122–6. doi:10.1111/j.1601-5037.2004.00083.x. PMID 16451475.
- ^ Sanchez, Isis R.; Swaim, Steven F.; Nusbaum, Kenneth E.; Hale, Anne S.; Henderson, Ralph A.; McGuire, John A. (1988). "Effects of Chlorhexidine Diacetate and Povidone-lodine on Wound Healing in Dogs". Veterinary Surgery 17 (6): 291–5. doi:10.1111/j.1532-950X.1988.tb01019.x. PMID 3232321.
- ^ Zeman, D; Mosley, J; Leslie-Steen, P (Winter 1996). "Post-Surgical Respiratory Distress in Cats Associated with Chlorhexidine Surgical Scrubs". ADDL Newsletters. Indiana Animal Disease Diagnostic Laboratory. Retrieved 2011-09-11.
- ^ McDonnell, J. "Deafness in Cats". PetPlace.com. Retrieved 2011-09-11.
- ^ Denton, Graham W (2000). "Chlorhexidine". In Block, Seymour S. Disinfection, Sterilization, and Preservation (5th ed.). Lippincott Williams & Wilkins. pp. 321–36. ISBN 978-0-683-30740-5.
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