‫‪Chlorhexidine‬‬

‫‪Prof.Dr.Hassan Abdelfattah‬‬

‫االسم‪:‬ادهم صالح مسلم نبوى الطحان‬

‫الفرقة‪:‬الرابعة‬
‫القسم‪:‬الكيمياء التطبيقية الصناعية‬

‫‪Chemotherapy‬‬
contents
1) Chlorhexidine
2) Synthesis
3) Mechanism of action
4) Uses
a) Antiseptic
b) Dental
c) Topical
5) Side effects
6) Precautions
7) Interactions
8) Overdose

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

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Synthesis

1. Starting Materials:

• 1,1'-Hexamethylenebis(5-(p-chlorophenyl)biguanide): This is a key intermediate in

chlorhexidine synthesis. It is typically prepared by reacting hexamethylenediamine with
p-chlorophenyl isocyanate.

2. Synthesis:

• Step 1: Preparation of Hexamethylenebis(p-chlorophenyl isocyanate):

• React hexamethylenediamine with p-chlorophenyl isocyanate to form 1,1'-

Hexamethylenebis(5-(p-chlorophenyl)biguanide).

H2N-(CH2)6-NH2 + 2 p-ClC6H4NCO → H2N-(CH2)6-N=C=O + 2 p-ClC6H4N=C=O + 2 HCl

• Step 2: Chlorination:

• Chlorinate the intermediate using thionyl chloride (SOCl2) or phosphorus

pentachloride (PCl5) to replace the amino groups with chlorine atoms. This step
introduces chlorines to the aromatic rings.

• By socl2

H2N-(CH2)6-N=C=O + 2 SOCl2 → Cl-(CH2)6-N=C=O + 2 SO2 + 2 HCl

• By pcl5

H2N-(CH2)6-N=C=O + 2 PCl5 → Cl-(CH2)6-N=C=O + 2 POCl3 + 2 HCl

• Step 3: Alkylation:

• Introduce the alkyl groups to the nitrogen atoms by reacting with a suitable
alkylating agent.

Cl-(CH2)6-N=C=O + R-X → R-(CH2)6-N=C=O + HX

Final Product:

• The final product is chlorhexidine, which is typically obtained as a white crystalline powder. The
chemical structure of chlorhexidine includes two biguanide groups linked by a hexamethylene
chain, with p-chlorophenyl rings and chlorines attached.

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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.

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). A 2019 Cochrane review concluded that
based on very low certainty evidence in those who are critically ill "it is not clear
whether bathing with chlorhexidine reduces hospital-acquired infections,
mortality, or length of stay in the ICU, or whether the use of chlorhexidine results
in more skin reactions.
In endodontics, chlorhexidine has been used for root canal irrigation and as an
intracanal dressing, but has been replaced by the use of sodium hypochlorite
bleach in much of the developed wo

a) Antiseptic
Chlorhexidine is active against Gram-positive and Gram-negative organisms,
facultative anaerobes, aerobes, and yeasts. 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.
There is strong evidence that chlorhexidine is more effective than povidone-
iodine for clean surgery.Evidence shows that it is an effective antiseptic for upper
limb surgery.
Meta-data spanning several decades shows that the efficacy of chlorhexidine
(against organisms that cause surgical site infection) has not changed, dispelling
concerns over emerging resistance.

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 b) Dental use
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. There is not
enough evidence to determine the effect in moderate to severe gingivitis.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. Extrinsic tooth
staining occurs when chlorhexidine rinse has been used for 4 weeks or longer.
Mouthwashes containing chlorhexidine which stain teeth less than the classic
solution have been developed, many of which contain chelated zinc.
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 2 hours after brushing".

c) 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. Chlorhexidine eye drops have been used as a treatment for eyes affected
by Acanthamoeba keratitis.
Chlorhexidine is very effective for poor countries like Nepal 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%.

Side effects
Chlorhexidine is ototoxic (toxic to the inner ear). If put into an ear canal which has a ruptured
eardrum, it can lead to deafness.
Chlorhexidine does not meet current 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. In the U.S., between 2007

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 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.

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.

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.

Precautions
Before using chlorhexidine, tell your doctor or pharmacist if you are allergic to it;
or if you have any other allergies. This product may contain inactive ingredients,
which can cause allergic reactions or other problems. Talk to your pharmacist for
more details.
Before using this medication, tell your doctor or pharmacist your medical history,
especially of: dental crowns, veneers, or fillings (especially if on the front teeth
and if made of porcelain).
Tell your doctor if you are pregnant before using this medication.
It is unknown if this drug passes into breast milk. Consult your doctor before
breast-feeding.

Interactions
Drug interactions may change how your medications work or increase your risk
for serious side effects. This document does not contain all possible drug
interactions. Keep a list of all the products you use (including
prescription/nonprescription drugs and herbal products) and share it with your
doctor and pharmacist. Do not start, stop, or change the dosage of any medicines
without your doctor's approval.

Overdose
If someone has overdosed and has serious symptoms such as passing out or
trouble breathing, call 911. Otherwise, call a poison control center right away. US
residents can call their local poison control center at 1-800-222-1222. Canada
residents can call a provincial poison control center.

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