Chlorhexidine

Chlorhexidine

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 Y
ATC code	A01AB03 B05CA02, D08AC02, D09AA12, R02AA05, S01AX09, S02AA09, S03AA04
PubChem	CID 5353524
DrugBank	APRD00545
ChemSpider	2612 Y
UNII	R4KO0DY52L Y
KEGG	D07668 Y
ChEBI	CHEBI:3614 Y
ChEMBL	CHEMBL790 Y
Chemical data
Formula	C22H30Cl2N10
Mol. mass	505.446 g/mol
SMILES	eMolecules & PubChem
InChI InChI=1S/C22H30Cl2N10/c23-15-5-9-17(10-6-15)31-21(27)33-19(25)29-13-3-1-2-4-14-30-20(26)34-22(28)32-18-11-7-16(24)8-12-18/h5-12H,1-4,13-14H2,(H5,25,27,29,31,33)(H5,26,28,30,32,34) Y Key:GHXZTYHSJHQHIJ-UHFFFAOYSA-N Y
N(what is this?)  (verify)

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. Chlorhexidine is harmful in high concentrations, but is used safely in low concentrations in many products, such as mouthwash and contact lens solutions.

Availability

Chlorhexidine is present in oral rinses and skin cleansers, and in small quantities it is used as a preservative.

It is sometimes marketed under the brand names Foam Safe, Hexicleans, Peridex, Periochip, Perichlor or Periogard Oral Rinse. In the UK it is mainly marketed under the brand name Corsodyl (or Chlorohex); in Italy as Curasept (Curaden Healthcare srl); in Germany as Chlorhexamed; in Australia and New Zealand as Savacol; in Greece as Chrolhexil (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.

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) and is also available as a wound wash. 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.

Dental

It 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.^[4] If it is not deactivated, chlorhexidine lasts longer in the mouth than other mouthwashes and this is partly why it is preferred over other treatments for gingivitis.^{[citation needed]}

Chlorhexidine-based products are commonly used to combat or prevent gum diseases such as gingivitis. According to Colgate,^{[5][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.^[6]

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.^[7]

There are oral pathologic conditions in which the maintenance of oral hygiene with the twice-daily use with 0.12% chlorhexidine-gluconate solution is required for healing and regeneration of the oral tissues. These conditions included gingivitis, periodontitis, dental traumas^[8] (such as subluxation), oral cysts,^[9] and after wisdom tooth extraction. Continued use of products containing chlorhexidine for long periods can cause stains on teeth, especially on silicate and resin restorations; prolonged use can also alter taste sensation - this latter symptom can be reversed by ceasing use of chlorhexidine.^[10] A version which stains the teeth less has been developed.^[11] Chlorhexidine is neutralized by common toothpaste additives such as sodium lauryl sulfate (SLS) and sodium monofluorophosphate (MFP). Although data is limited, to maximize effectiveness it may be best to keep a 30-minute to 2-hour interval between brushing and using the mouthwash.^[12]

Topical

Chlorhexidine is also used in nondental applications, most notably under the brand names Foam Safe, Hexicleans,Tipset sachets (sterets), Oronine, Avagard, Hibiclens, Savinox plus (Bioshields), Hibiscrub, ChloraPrep, ChloraScrub, BIOPATCH, SOLU-I.V. and Exidine. It is also a component of the household antiseptic Savinox plus (Bioshields), Termilon(Mil Laboratories Pvt Ltd) and Savlon. It is used for general skin cleansing, a surgical scrub, and a pre-operative skin preparation. Due to other chemicals listed as inactive ingredients, most cleansers are not recommended for use as mouthwash though some originally were used prior to the development of oral alternatives. 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. It is more effective in killing bacteria than both povidone-iodine and saline, and has residual effects up to 6 hours. 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.^[13] Note, however, that problems^[14] including deafness^[15] have been associated with the use of chlorhexidine products in cats. It is commonly used to manage skin infections in dogs.

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.^[16] 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 santitizers 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.^[2]

References

1. ^ "Chlorhexidine". Drugs.com. August 2011. http://www.drugs.com/pro/chlorhexidine.html. Retrieved 2011-09-11. 
2. ^ ^{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. http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/MSM_98_4/en/. Retrieved 2010-09-11. 
3. ^ Kuyyakanond, T; Quesnel, LB; Selkirk, S; Poole, S (1992). "The mechanism of action of chlorhexidine". FEMS Microbiology Letters 79 (1–3): 211–215. doi:10.1111/j.1574-6968.1991.tb04531.x. PMID 1335944. 
4. ^ 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. 
5. ^ "Colgate Periogard Rinse (Rx only)". Colgate. http://www.colgateprofessional.com/products/Colgate-Periogard-Rinse-Rx-only/specifics. Retrieved 2011-09-12. 
6. ^ 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. 
7. ^ Autio-Gold, J (2008). "The role of chlorhexidine in caries prevention". Operative Dentistry 33 (6): 710–6. doi:10.2341/08-3. PMID 19051866. 
8. ^ Zadik, Y (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. 
9. ^ Zadik, Y; Yitschaky, O; Neuman, T; Nitzan, DW (2011). "On the Self-Resolution Nature of the Buccal Bifurcation Cyst". Journal of Oral and Maxillofacial Surgery 20 (5): e282–4. doi:10.1016/j.joms.2011.02.124. PMID 21571416. 
10. ^ Helms, JA; Della-Fera, MA; Mott, AE; Frank, ME (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. 
11. ^ 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. 
12. ^ 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. 
13. ^ Sanchez, IR; Swaim, SF; Nusbaum, KE; Hale, AS; Henderson, RA; McGuire, JA (1988). "Effects of chlorhexidine diacetate and povidone-iodine on wound healing in dogs". Veterinary Surgery 17 (6): 291–5. doi:10.1111/j.1532-950X.1988.tb01019.x. PMID 3232321. 
14. ^ 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. http://www.addl.purdue.edu/newsletters/1996/winter/psrd.shtml. Retrieved 2011-09-11. 
15. ^ McDonnell, J. "Deafness in Cats". PetPlace.com. http://www.petplace.com/cats/deafness-in-cats/page2.aspx. Retrieved 2011-09-11. 
16. ^ Denton, W (2001). "Chlorhexidine". In Block, SS. Sterilisation and Preservation (5th ed.). Lippincott Williams & Wilkins. pp. 321–36. ISBN 978-0-683-30740-5. 

External links

• FDA Professional Drug Information