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History 3. Structure: 4. Chlorhexidine - Based Products
History 3. Structure: 4. Chlorhexidine - Based Products
History 3. Structure: 4. Chlorhexidine - Based Products
1. Introduction
2. History
3. Structure
5. Mechanism of action
6. Chlorhexidine Staining
7. Toxicology
8. Clinical Uses
9. Conclusion
10.Reference
INTRODUCTION
Chlorhexidine is a
bisbiguanide formulation with
cationic
properties. The molecule is
symmetric with two
chlorophenyle rings and two
bigunide groups connected by
a
central hexamethylene chain.
It is a strong base and is most
stable in the form of salts.
The most common
preparation is
the digluconate salt because of
its water solubility
Chlorhexidine is a
bisbiguanide formulation with
cationic
properties. The molecule is
symmetric with two
chlorophenyle rings and two
bigunide groups connected by
a
central hexamethylene chain.
It is a strong base and is most
stable in the form of salts.
The most common
preparation is
the digluconate salt because of
its water solubility
Chlorhexidine is a
bisbiguanide formulation with
cationic
properties. The molecule is
symmetric with two
chlorophenyle rings and two
bigunide groups connected by
a
central hexamethylene chain.
It is a strong base and is most
stable in the form of salts.
The most common
preparation is
the digluconate salt because of
its water solubility
Chlorhexidine is a
bisbiguanide formulation with
cationic
properties. The molecule is
symmetric with two
chlorophenyle rings and two
bigunide groups connected by
a
central hexamethylene chain.
It is a strong base and is most
stable in the form of salts.
The most common
preparation is
the digluconate salt because of
its water solubility
Chlorhexidine is a
bisbiguanide formulation with
cationic
properties. The molecule is
symmetric with two
chlorophenyle rings and two
bigunide groups connected by
a
central hexamethylene chain.
It is a strong base and is most
stable in the form of salts.
The most common
preparation is
the digluconate salt because of
its water solubility
Chlorhexidine is a
bisbiguanide formulation with
cationic
properties. The molecule is
symmetric with two
chlorophenyle rings and two
bigunide groups connected by
a
central hexamethylene chain.
It is a strong base and is most
stable in the form of salts.
The most common
preparation is
the digluconate salt because of
its water solubility
Chlorhexidine is a
bisbiguanide formulation with
cationic
properties. The molecule is
symmetric with two
chlorophenyle rings and two
bigunide groups connected by
a
central hexamethylene chain.
It is a strong base and is most
stable in the form of salts.
The most common
preparation is
the digluconate salt because of
its water solubility
Chlorhexidine is a bisbiguanide formulation with cationic properties . The
molecule is symmetric with two chlorophenyle rings and two bigunide groups
connected by a central hexamethylene chain . It is a strong base and is most
stable in the form of salts . The most common preparation is the digluconate salt
because of its water solubility.1
Chlorhexidine is a bisbiguanide
formulation with cationic
properties. The molecule is symmetric
with two
chlorophenyle rings and two bigunide
groups connected by a
central hexamethylene chain. It is a
strong base and is most
stable in the form of salts. The most
common preparation is
the digluconate salt because of its water
solubility
Chlorhexidine is an ideal broad-spectrum antimicrobial. It is effective against
Gram-positive bacteria, Gram-negative bacteria and fungi. These organisms are
commonly associated with Healthcare-Associated Infections (HAIs).With its low
toxicity level, chlorhexidine offers a safe side effect profile. For nearly 60 years,
chlorhexidine has been used by hospitals and clinics as a disinfectant and
antiseptic for topical and hard-surface applications. Chlorhexidine has become an
integral part of the strategy to prevent the transmission of disease and
nosocomial infections. Chlorhexidine is used to kill bacteria that cause infections.
It is found in many medicines that are applied directly to the affected area of the
body. It is an antiseptic treatment. It is used to treat and prevent infections. In
general this drug is used where infections of the skin, mouth or throat are
present or may arise. The treatment and prevention of infections of minor cuts,
grazes, burns and scalds, athlete’s foot, blisters, stings and insect bites, spots,
chapped or rough skin and minor infections of the mouth or throat. It is also used
for cleaning the skin before injections and small operations. 2
The available formulations of chlorhexidine are gels, chips, sprays, varnishes, and
mouthwashes. It is commonly preferred among dentists. The clinical effect of
chlorhexidine is likely due to both its substantive and antibacterial properties
Chlorhexidine has a wide variety of usefulness in oral health care. It is used in the
management of oral hygiene, dental plaque, dental caries, gingivitis,
periodontitis, peri-implantitis, irrigating agent, pre-procedural mouth rinse, and
management of oral mucosal diseases. The presence of bacteria in dental plaque
or oral biofilm produces host inflammatory response of gingiva and
periodontium resulting in gingivitis and periodontitis respectively. Chlorhexidine
is used as a mouthwash against plaque-producing bacteria. It should always be
used along with mechanical plaque control measures such as tooth brushing and
interdental aids, as an adjunct, as suggested by the European Federation of
Periodontology (EFP). Reduction in clinical signs of gingivitis and periodontitis has
been shown in studies with the use of 0.2% CHX mouthwash for 4-6 weeks .
When chlorhexidine is used as a mouth wash, it should be used 30 minutes to 2
hours after tooth brushing as it could interact with the anionic compounds of the
toothpaste and it could nullify the effect of fluoride that is present in toothpaste .
The use of chlorhexidine mouth rinse (0.2%) could potentially reduce plaque
formation and eventually results in a low incidence of caries. Chlorhexidine is a
commonly used antiseptic mouthwash due to its antimicrobial effects..3
HISTORY
HISTORY OF MOUTH RINSE
The first reference to mouth rinsing as a formal practice is credited to Chinese medicine,
about 2700 B.C.E. Recommendation was rinsing with the urine of a child. Mouth rinsing as
an adjunct to mechanical cleansing became popular with the upper classes in the Roman
period. Pliny recommended salty water used in an uneven number of Mouthfuls.
Hippocrates advocated a mixture of salt, alum and vinegar. Other included a mixture of
honey, oil and beer and a combination of dill, anise seed, myrrh and pure white wine.
“Therapeutic rinsing” was especially popular among the Europeans, and persisted until the
early 18th century. Mouth rinsing also had a religious connection. The Talmud contains
instructions for rinsing the mouth between meals to remove food remnants and prevent
admixing of meat and milk products, a violation of the dietary laws. Mechanical tooth
cleaning and mouth rinsing were established practices by the 16th century. 4
The Zene Artzney (Medicines for the Teeth), published in Germany in 1530, contained a
section on “How to save the teeth’. The recommendations included washing the mouth
with burnt alum mixed with vinegar or myrrh boiled in wine. The final suggestion was
“always after eating, wash the mouth with wine or beer, in order to wash away all that
might adhere to the teeth and make them decay, produce bad odor, and destroy them”.
W.D. Miller, in support of his Chemo parasitic theory of tooth decay, pointed out - There
are places around every dentition which will remain untouched by even the most thorough
application of an antiseptic, or the antiseptic will reach them in so diluted a condition that
it possesses little or no action.4
1. Group A Mouth washes : With good substantivity and antibacterial spectrum and good
anti-plaque effects. Agents with these properties are the bisguanides (the best of which is
chlorhexidine), salifluor and delmopinol.
2. Group B Mouth washes : With little or no substantivity but with a good antibacterial
spectrum. Therefore, they have plaque inhibitory effects. These include Cetyl pyridinium
chloride, Essential oil/ phenolic mouthwash, Listerine, Triclosan. They cannot be used to
replace tooth brushing but can be used as adjuvants to mechanical cleaning.
3. Group C Mouthwashes : With antibacterial, varying plaque inhibitory effects from
moderate to low or no. These include Hexetidine (Oraldene), Povidone iodine, Oxygenating
agents, Sanguinarine. These have limited or no adjuvant effects when combined with
mechanical cleaning and therefore cannot be recommended for this purpose.
HISTORY OF CHLORHEXIDINE
In 1947, a complex study to synthesize new antimalarial agents led to the development of the
polybiguanides. These compounds showed significant antimicrobial potential. Davies et al
(1954) demonstrated that this compound had bacteriostatic activity, especially against Gram-
positive bacteria (linked to the central hexamethylene unit and the terminal benzene ring) and
bactericidal activity (depending on the concentration). This compound did not modify the
action of penicillin, streptomycin,chloramphenicol, oxytetracyline. Experimental studies in
albino mice revealed a low degree of toxicity at 10 days after the subcutaneous,
intraperitoneal, intravenous or oral administration of a single dose of Chlorhexidine, as well as
after a year of continuous oral administration. Chlorhexidine was developed in the 1940s by
Imperial Chemical Industries, England, and marketed in 1954 as an antiseptic for skin wounds.
(As Hibitane) . 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 endodontics.
Plaque inhibition by chlorhexidine was first investigated in 1969 (Schroeder 1969). The
definitive study was performed by Loe and Schiott (1970).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.4
STRUCTURE
Chemical structure Chlorhexidine is an amphipathic molecule with hydrophilic and
hydrophobic groups. Synthesized from proguanil and belongs to the biguanide family, a group
of compounds with antimalarial activity. Chlorhexidine is a bisbiguanide antiseptic; being a
symmetrical molecule consisting of two chlorophenyl rings and two biguanide groups
connected by a central hexamethylene bridge.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.
Chlorhexidine is available in three formsDigluconate,Acetate, Hydrochloride salts(as base
molecule is insoluble in water). Most studies and most oral formulations and products have
used the digluconate salt, which is manufactured as a 20% volume of solute / volume of
solution concentrate. Digluconate a acetate salts are water-soluble but hydrochloride is very
sparingly soluble in water.4
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Chlorhexidine is available in three forms :
Mouth rinses
Aqueous alcohol solutions of 0.2% chlorhexidine were first made available for
mouth rinse products for twice daily use in Europe in the 1970s. The studies
revealed equal efficacy for 0.2% and 0.12% rinses when used at appropriate
similar doses ( Segreto et al. 1986).More recently alcohol free chlorhexidine
mouth rinses have been available .This possess equivalent effects of inhibiting
plaque and gingivitis compared to alcohol containing but with better taste
acceptability.
Various mouth rinses
Peridex oral rinse (0.12%) 3M, Periogard (0.12%) Colgate, Hexide (0.2%) Deys
medical, Rexidin (0.2%) Indico remedies ltd., Hexiklin (0.2%) Simpson Brawn
pharma, Hexiclo (0.2%) Sunways India Pvt Ltd, Hexidine (0.2%) Icpa Health
Products Ltd, Clohex (0.2%) Dr Reddy's Laboratories Ltd, Haa mouth wash (0.2%)
Cadila Pharmaceuticals Ltd.
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 (Saxen et al. 1976). In trays the chlorhexidine gel was found to be
particularly effective against plaque and gingivitis in handicapped individuals
(Francis et al 1987). The acceptability of this tray delivery system to the
recipients and the careers was found to be poor. 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% mouth rinses (Kalaga et al 1989) Sprays appear
useful for the physically and mentally handicapped.(Francis et al 1987, Kalaga et
al 1989) .
Toothpaste
Chlorhexidine is difficult to formulate into toothpaste. Chlorhexidine products
based on toothpaste and sprays produces similar tooth staining to mouth rinses
and gels; taste disturbance, mucosal erosion and parotid swellings tend to be less
or have never been reported.
Varnishes
Chlorhexidine varnishes have been used mainly for prophylaxis against root
caries rather than an antiplaque depot for chlorhexidine in the mouth.
MECHANISM OF ACTION
The bacterial cell wall is negatively charged and contain sulphates and
phosphates.
After the integrity of the bacterial cell membrane and chlorhexidine is attracted
to the inner cell membrane.
Antibacterial action
Antibacterial n
actio
Antibacterialaction
The positive charges of chlorhexidine molecule are present over the nitrogen
atoms on the sides of the hexamethylene bridge.At low concentration,
chlorhexidine damages the cellular transport of the bacterial cell by creating
pores in the cellular membrane.In higher concentration, chlorhexidine
penetrates the bacterial cell and causes bacteriolysis.10
Anti-plaque effect
The substantivity of chlorhexidine made it a more suitable antimicrobial agent
for the inhibition of plaque.The chlorhexidine affects the pellicle formation by
blocking the acidic groups on the salivary glycoproteins. There is a reduction in
the protein adsorption to the tooth surface. Chlorhexidine binds to the bacterial
surface and thus reduces the formation of plaque by precipitating the
agglutination factors in saliva and displaces the calcium.10
Bactericidal effect
CHLORHEXIDINE STAINING
Gold standard
Superior antiplaque effect - in terms of its superior degree of persistence at the
tooth surface. Superior persistence of antibacterial effect (both bactericidal and
bacteriostatic) at the tooth surface. One charged end of the chlorhexidine
molecule binding to the tooth surface and the other remaining available to
initiate the interaction with the bacterial membrane as the microorganism
approaches the tooth surface – a “Pin-Cushion’’ effect.4
The cationic nature of chlorhexidine minimizes absorption through the skin and
mucosa, including from the gastrointestinal tract. Primary route of excretion is through
faeces. Systemic toxicity from topical application or ingestion is not reported. (poorly
absorbed by GIT, oral LD is 1800mg/kg ). Even in intravenous infusion in animals,
chlorhexidine is well tolerated. (Intravenous LD is 22mg/kg). No tetragenic alterations
have been found.2 Neurosensory deafness can occur if chlorhexidine is introduced into
the middle ear and the antiseptic should not be placed in the outer ear in case the
eardrum is perforated. In oral use as a mouth rinse, chlorhexidine has been reported to
have a number of local side effects (Flotra et al. 1971). 4
1. Brown discoloration of the teeth and some restorative materials and the dorsum of
the tongue (Dose dependent).
Chlorhexidine also has a bitter taste, which is difficult to mask completely.6 for these
reasons; the prolonged use of chlorhexidine should be avoided. It is useful for short
periods of up to 2 weeks.4
CLINICAL USES
Despite the excellent plaque inhibitory properties of chlorhexidine, widespread and
prolonged use of the agent is limited by local side effects. Moreover, because of the
cationic nature of the chlorhexidine and therefore its poor penetrability, the antiseptic
is of limited value in the therapy of established oral conditions including gingivitis, and
is much more valuable in the preventive mode. A number of clinical uses, some well
researched, have been recommended for chlorhexidine.11
Oral hygiene instruction is a key factor in the treatment plan for patients with
periodontal disease and as part of the maintenance program following
treatment. Adequate plaque control by periodontal patients is therefore
essential to successful treatment and the prevention of re-occurrence of the
disease. Chlorhexidine should therefore increase the improvement in gingival
health through plaque control, particularly following a professional prophylaxis
to remove existing supra and immediately subgingival plaque. There is, however,
a potential disadvantage of using such an effective chemical plaque control agent
at this stage of the periodontal treatment plan. Thus, following oral hygiene
instruction, it is normal, usually by the use of indices, to quantify the
improvement in plaque control by patients so instructed and, in particular, the
improvement at specific sites which previously had been missed by individual
patients. By virtue of the excellent plaque control effects of chlorhexidine, the
response to oral hygiene instruction cannot be accurately assessed since the
antiseptic will overshadow any deficiencies in mechanical cleaning. Indeed, as
the original research demonstrated, patients could maintain close to zero levels
of plaque following a professional prophylaxis without using any form of
mechanicaloral hygiene.11
POST-ORAL SURGERY INCLUDING PERIODONTAL SURGERY OR ROOT PLANNING
Chlorhexidine may be used postoperatively since it offers the advantage of
reducing the bacterial load in the oral cavity and preventing plaque formation at
a time when mechanical cleaning may be difficult because of discomfort. In
periodontal surgery, periodontal dressings have largely been replaced by the use
of chlorhexidine preparations, in particular mouthrinses, since healing is
improved and discomfort reduced (Newman & Addy 1978, 1982). Regimens vary
but chlorhexidine should be used immediately post treatment and for periods of
time until the patient can reinstitute normal oral hygiene. Depending on
theappointment schedule, chlorhexidine could be usedthroughout the treatment
phase and for periods of weeks after completion of the treatment plan. If
dressings are used, chlorhexidine is of limited value to the postoperative site
since it does not penetrate beneath
the periodontal dressings (Pluss et al. 1975). The idea of full mouth disinfection
using chlorhexidine both supra and subgingivally has recently been assessed by
one group of researchers (Quirynen et al. 1995). In the event, few adjunctive
benefits could be shown and it appeared that the more dominant factor was the
time over which the non-surgical treatment plan was completed.Thus, root
planing performed totally within 24 hours was more effective than root planing
completed over more conventional periods of several weeks.11
Oral hygiene is particularly difficult when jaws are immobilized by such methods
as intermaxillary fixation. Chlorhexidine has been shown to reduce markedly
the bacterial load, which tends to increase during jaw immobilization, and
improve plaque control (Nash & Addy 1979).11
FOR ORAL HYGIENE AND GINGIVAL HEALTH BENEFITS IN THE MENTALLY AND
PHYSICALLY HANDICAPPED
IN DENTURE STOMATITIS
SUBGINGIVAL IRRIGATION
Table 1
Adjunctive uses of chlorhexidine products in the treatment of stage I-III
periodontitis.14
Side Effects : Brown discolouration of the teeth , restorative materials and yellow discoloration
oftongue . * The mechanisms proposed for CHX staining can be debated ( Eriksen et al . 1985 ,
Addy & Moran 1995 , Watts & Addy 2001 ) but have been proposed as : 1. Degradation ofthe
chlorhexidine molecule to release parachloraniline . [ ( Addy and Roberts 1981 )
reference