Chlorhexidine

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Chlorhexidine
Chlorhexidin.svg
Chlorhexidine 3D spacefill.png
Clinical data
Pronunciationklɔː(r)ˈhɛksɪdiːn
Trade names Betasept, ChloraPrep, Chlorostat, others
Other namesCHX, CHG, 1,6-bis(4-chloro-phenylbiguanido)hexane
AHFS/Drugs.com Monograph
License data
Pregnancy
category
  • AU:A
Routes of
administration
Topical
ATC code
Legal status
Legal status
  • AU:S5, S6, S7
  • US: OTC / Rx-only
Identifiers
  • N,N1,6-Hexanediylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.217 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H30Cl2N10
Molar mass 505.45 g·mol−1
3D model (JSmol)
Melting point 134 to 136 °C (273 to 277 °F)
Solubility in water 0.8
  • Clc1ccc(NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)Nc2ccc(Cl)cc2)cc1
  • 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) Yes check.svgY
  • Key:GHXZTYHSJHQHIJ-UHFFFAOYSA-N Yes check.svgY
   (verify)

Chlorhexidine [1] is a disinfectant and antiseptic with the molecular formula C22H30Cl2N10, which is used for skin disinfection before surgery and to disinfect surgical instruments. [2] It is also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and to keep urinary catheters from blocking. [3] It is used as a liquid or a powder. [2] [3] It is commonly used in salt form, either the gluconate [4] or the acetate. [5]

Contents

Side effects may include skin irritation, tooth discoloration, and allergic reactions, [3] although, apart from discoloration, the risk appears to be the same as that for povidone-iodine. [6] [7] Chlorhexidine rinse is also known to have a bitter metallic aftertaste. Rinsing with water is not recommended as it is known to increase the bitterness. [8] It may cause eye problems if direct contact occurs. [9] [10] Use in pregnancy appears to be safe. [11] Chlorhexidine may come mixed in alcohol, [12] [13] [14] water, or surfactant solution. [3] It is effective against a range of microorganisms, but does not inactivate spores. [2]

Chlorhexidine came into medical use in the 1950s [15] and is available over the counter in the United States. [9] It is on the World Health Organization's List of Essential Medicines. [16] [17] In 2021, it was the 247th most commonly prescribed medication in the United States, with more than 1 million prescriptions. [18] [19]

Uses

Chlorhexidine is used in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eye drops, active substance in wound dressings and antiseptic mouthwashes). [20]

In endodontics, chlorhexidine has been used for root canal irrigation and as an intracanal dressing. [21] [22]

Antiseptic

Chlorhexidine is active against Gram-positive and Gram-negative organisms, facultative anaerobes, aerobes, and yeasts. [23] It is particularly effective against Gram-positive bacteria (in concentrations ≥ 1 μg/L). Significantly higher concentrations (10 to more than 73 μg/mL) are required for Gram-negative bacteria and fungi. Chlorhexidine is ineffective against polioviruses and adenoviruses. The effectiveness against herpes viruses has not yet been established unequivocally. [24]

There is strong evidence that chlorhexidine is more effective than povidone-iodine for clean surgery. [25] [26] Evidence shows that it is an effective antiseptic for upper limb surgery. [6]

Meta-data spanning several decades shows that the efficacy of chlorhexidine (against organisms that cause surgical site infection) has not changed, [27] dispelling concerns over emerging resistance.

Dental use

Perichlor brand 0.12% chlorhexidine gluconate solution Perichlor, 0.12%25 chlorhexidine glucomate solution medication.jpg
Perichlor brand 0.12% chlorhexidine gluconate solution

Use of a chlorhexidine-based mouthwash in combination with normal tooth care can help reduce the build-up of plaque and improve mild gingivitis. [28] There is not enough evidence to determine the effect in moderate to severe gingivitis. [28] Its use as a mouthwash has a number of adverse effects including damage to the mouth lining, tooth discoloration, tartar build-up, and impaired taste. [28] Extrinsic tooth staining occurs when chlorhexidine rinse has been used for four weeks or longer. [28]

Mouthwashes containing chlorhexidine which stain teeth less than the classic solution have been developed, many of which contain chelated zinc. [29] [30] [31]

Chlorhexidine is a cation which interacts with anionic components of toothpaste, such as sodium lauryl sulfate and sodium monofluorophosphate, and forms salts of low solubility and reduced antibacterial activity. Hence, to enhance the antiplaque effect of chlorhexidine, "it seems best that the interval between toothbrushing and rinsing with CHX [chlorhexidine] be more than 30 minutes, cautiously close to two hours after brushing". [32]

Topical

Chlorhexidine gluconate is used as a skin cleanser for surgical scrubs, as a cleanser for skin wounds, for preoperative skin preparation, and for germicidal hand rinses. [23] Chlorhexidine eye drops have been used as a treatment for eyes affected by Acanthamoeba keratitis. [33]

Chlorhexidine is a very effective antiseptic and its use is growing in the world for treating the umbilical cord. A 2015 Cochrane review has yielded high-quality evidence that within the community setting, chlorhexidine skin or cord care can reduce the incidence of omphalitis (inflammation of the umbilical cord) by 50% and neonatal mortality by 12%. [34]

Side effects

Side effects may include skin irritation, tooth discoloration, and allergic reactions, [3] although apart from discoloration the risk appears to be the same as povidone-iodine. [6] [7]

Chlorhexidine is ototoxic (toxic to the inner ear). If put into a ruptured ear canal it may lead to deafness. [35]

Chlorhexidine does not meet European specifications for a hand disinfectant. Under the test conditions of the European Standard EN 1499, no significant difference in the efficacy was found between a 4% solution of chlorhexidine digluconate and soap. [24] In the US, between 2007 and 2009, Hunter Holmes McGuire Veterans Administration Medical Center conducted a cluster-randomized trial and concluded that daily bathing of patients in intensive care units with washcloths saturated with chlorhexidine gluconate reduced the risk of hospital-acquired infections. [36]

Whether prolonged exposure over many years may have carcinogenic potential is still not clear. The US Food and Drug Administration recommendation is to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months. [37]

When ingested, chlorhexidine is poorly absorbed in the gastrointestinal tract and can cause stomach irritation or nausea. [38] [39] If aspirated into the lungs at high enough concentration, as reported in one case, it can be fatal due to the high risk of acute respiratory distress syndrome. [39] [40]

Mechanism of action

At physiologic pH, chlorhexidine salts dissociate and release the positively charged chlorhexidine cation. The bactericidal effect is a result of the binding of this cationic molecule to negatively charged bacterial cell walls. At low concentrations of chlorhexidine, this results in a bacteriostatic effect; at high concentrations, membrane disruption results in cell death. [23]

Chemistry

It is a cationic polybiguanide (bisbiguanide). [41]

Deactivation

Chlorhexidine is deactivated by forming insoluble salts with 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. [42]

Synthesis

The structure is based on two molecules of proguanil, linked with a hexamethylenediamine spacer.

Two routes for chlorhexidine synthesis: U.S. patent 2,684,924 (1954 to I.C.I.). The compounds designated (...)2 are substituted hexanes. Chlorhexidine synthesis.png
Two routes for chlorhexidine synthesis: U.S. patent 2,684,924 (1954 to I.C.I.). The compounds designated (...)2 are substituted hexanes.

Society and culture

Brands

Chlorhexidine topical is sold as Betasept, Biopatch, Calgon Vesta, ChloraPrep One-Step, Dyna-Hex, Hibiclens, Hibistat Towelette, Scrub Care Exidine, Spectrum-4 among others. [44]

Chlorhexidine gluconate mouthwash is sold as Dentohexin, Paroex, Peridex, PerioChip, Corsodyl and Periogard, among others. [45]

Veterinary medicine

In animals, chlorhexidine is used for topical disinfection of wounds, [46] and to manage skin infections. [47] Chlorhexidine-based disinfectant products are used in the dairy farming industry. [48]

Post-surgical respiratory problems have been associated with the use of chlorhexidine products in cats. [49]

Related Research Articles

<span class="mw-page-title-main">Mouthwash</span> Liquid rinse for oral hygiene

Mouthwash, mouth rinse, oral rinse, or mouth bath is a liquid which is held in the mouth passively or swirled around the mouth by contraction of the perioral muscles and/or movement of the head, and may be gargled, where the head is tilted back and the liquid bubbled at the back of the mouth.

A bactericide or bacteriocide, sometimes abbreviated Bcidal, is a substance which kills bacteria. Bactericides are disinfectants, antiseptics, or antibiotics. However, material surfaces can also have bactericidal properties based solely on their physical surface structure, as for example biomaterials like insect wings.

<span class="mw-page-title-main">Listerine</span> Brand of mouthwash

Listerine is a brand of antiseptic mouthwash that is promoted with the slogan "Kills germs that cause bad breath". Named after Joseph Lister, who pioneered antiseptic surgery at the Glasgow Royal Infirmary in Scotland, Listerine was developed in 1879 by Joseph Lawrence, a chemist in St. Louis, Missouri.

An antiseptic is an antimicrobial substance or compound that is applied to living tissue to reduce the possibility of sepsis, infection or putrefaction. Antiseptics are generally distinguished from antibiotics by the latter's ability to safely destroy bacteria within the body, and from disinfectants, which destroy microorganisms found on non-living objects.

<span class="mw-page-title-main">Toothpaste</span> Substance to clean and maintain teeth

Toothpaste is a paste or gel dentifrice used with a toothbrush to clean and maintain the aesthetics and health of teeth. Toothpaste is used to promote oral hygiene: it is an abrasive that aids in removing dental plaque and food from the teeth, assists in suppressing halitosis, and delivers active ingredients to help prevent tooth decay and gum disease (gingivitis). Owing to differences in composition and fluoride content, not all toothpastes are equally effective in maintaining oral health. The decline of tooth decay during the 20th century has been attributed to the introduction and regular use of fluoride-containing toothpastes worldwide. Large amounts of swallowed toothpaste can be poisonous. Common colors for toothpaste include white and blue.

Teeth cleaning is part of oral hygiene and involves the removal of dental plaque from teeth with the intention of preventing cavities, gingivitis, and periodontal disease. People routinely clean their own teeth by brushing and interdental cleaning, and dental hygienists can remove hardened deposits (tartar) not removed by routine cleaning. Those with dentures and natural teeth may supplement their cleaning with a denture cleaner.

<span class="mw-page-title-main">Tincture of iodine</span> Antiseptic solution rubbed on skin before surgical operations

Tincture of iodine, iodine tincture, or weak iodine solution is an antiseptic. It is usually 2 to 3% elemental iodine, along with potassium iodide or sodium iodide, dissolved in a mixture of ethanol and water. Tincture solutions are characterized by the presence of alcohol. It was used from 1908 in pre-operative skin preparation by Italian surgeon Antonio Grossich.

<span class="mw-page-title-main">Povidone-iodine</span> Antiseptic solution

Povidone-iodine (PVP-I), also known as iodopovidone, is an antiseptic used for skin disinfection before and after surgery. It may be used both to disinfect the hands of healthcare providers and the skin of the person they are caring for. It may also be used for minor wounds. It may be applied to the skin as a liquid, an ointment or a powder.

Dental plaque is a biofilm of microorganisms that grows on surfaces within the mouth. It is a sticky colorless deposit at first, but when it forms tartar, it is often brown or pale yellow. It is commonly found between the teeth, on the front of teeth, behind teeth, on chewing surfaces, along the gumline (supragingival), or below the gumline cervical margins (subgingival). Dental plaque is also known as microbial plaque, oral biofilm, dental biofilm, dental plaque biofilm or bacterial plaque biofilm. Bacterial plaque is one of the major causes for dental decay and gum disease.

<span class="mw-page-title-main">Hand sanitizer</span> Alternative to hand washing

Hand sanitizer is a liquid, gel, or foam used to kill viruses, bacteria, and other microorganisms on the hands. It can also come in the form of a cream, spray, or wipe. While hand washing with soap and water is generally preferred, hand sanitizer is a convenient alternative in settings where soap and water are unavailable. However, it is less effective against certain pathogens like norovirus and Clostridioides difficile and cannot physically remove harmful chemicals. Improper use, such as wiping off sanitizer before it dries, can also reduce its effectiveness, and some sanitizers with low alcohol concentrations are less effective. Additionally, frequent use of hand sanitizer may disrupt the skin's microbiome and cause dermatitis.

<span class="mw-page-title-main">Cetylpyridinium chloride</span> Chemical compound

Cetylpyridinium chloride (CPC) is a cationic quaternary ammonium compound used in some types of mouthwashes, toothpastes, lozenges, throat sprays, breath sprays, and nasal sprays. It is an antiseptic that kills bacteria and other microorganisms. It has been shown to be effective in preventing dental plaque and reducing gingivitis. It has also been used as an ingredient in certain pesticides. As of the time of this update, one study suggests cetylpyridinium chloride does not cause brown tooth stains, although particular questions regarding usage habits in patient context are best addressed by a dental office as opposed to legal marketing. There are brands containing CPC as an active ingredient that may bear the warning label "In some cases, antimicrobial rinses may cause surface staining to teeth," following a failed class-action lawsuit brought by customers whose teeth were stained.

<span class="mw-page-title-main">Scaling and root planing</span> Dental procedure

Scaling and root planing, also known as conventional periodontal therapy, non-surgical periodontal therapy or deep cleaning, is a procedure involving removal of dental plaque and calculus and then smoothing, or planing, of the (exposed) surfaces of the roots, removing cementum or dentine that is impregnated with calculus, toxins, or microorganisms, the agents that cause inflammation. It is a part of non-surgical periodontal therapy. This helps to establish a periodontium that is in remission of periodontal disease. Periodontal scalers and periodontal curettes are some of the tools involved.

<span class="mw-page-title-main">Oral hygiene</span> Cleaning the mouth by brushing the teeth and cleaning in between the teeth

Oral hygiene is the practice of keeping one's oral cavity clean and free of disease and other problems by regular brushing of the teeth and adopting good hygiene habits. It is important that oral hygiene be carried out on a regular basis to enable prevention of dental disease and bad breath. The most common types of dental disease are tooth decay and gum diseases, including gingivitis, and periodontitis.

A virucide is any physical or chemical agent that deactivates or destroys viruses. The substances are not only virucidal but can be also bactericidal, fungicidal, sporicidal or tuberculocidal.

<span class="mw-page-title-main">Gingivitis</span> Inflammation of the gums

Gingivitis is a non-destructive disease that causes inflammation of the gums; ulitis is an alternative term. The most common form of gingivitis, and the most common form of periodontal disease overall, is in response to bacterial biofilms that are attached to tooth surfaces, termed plaque-induced gingivitis. Most forms of gingivitis are plaque-induced.

Octenidine dihydrochloride is a cationic surfactant, with a gemini-surfactant structure, derived from 4-aminopyridine. It is active against Gram-positive and Gram-negative bacteria. Since 1987, it has been used primarily in Europe as an antiseptic prior to medical procedures, including on neonates.

Skin disinfection is a process that involves the application of a disinfectant to reduce levels of microorganisms on the skin. Disinfecting the skin of the patient and the hands of the healthcare providers are an important part of surgery.

<span class="mw-page-title-main">Alcohols (medicine)</span> Alcohols used as antiseptics, disinfectants or antidotes

Alcohols, in various forms, are used medically as an antiseptic, disinfectant, and antidote. Alcohols applied to the skin are used to disinfect skin before a needle stick and before surgery. They may also be used as a hand sanitizer; to clean other areas; and in mouthwashes. Taken by mouth or injected into a vein, ethanol is used to treat methanol or ethylene glycol toxicity when fomepizole is not available.

Decolonization, also bacterial decolonization, is a medical intervention that attempts to rid a patient of an antimicrobial resistant pathogen, such as methicillin-resistant Staphylococcus aureus (MRSA) or antifungal-resistant Candida.

<span class="mw-page-title-main">Salt rinse</span> Saline solution mouthwash

Salt rinse is a saline solution mouthwash used in dentistry to treat certain diseases and reduce post-operative pain and infection. It is also offered commercially for routine oral hygiene. Other names for the treatment include salt water mouthwash, salt water mouth bath, and saline mouth rinse.

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