‫بسم الله الرحمن الرحيم‬

Chemotherapeutic agents in periodontal diseases

Today we will talk about the antibiotics and mainly the systemic.

The idea of treating the periodontal disease by antibiotics came from the fact that this
disease is bacterial disease, but the problem is from the cause that is the plaque, this
plaque is composed of biofilm that contains layers of bacteria that are communicating
with each other in the pocket, so this feature of biofilm make it difficult for the
antimicrobial to reach the bacteria in effective concentration, so the most effective
treatment of periodontal disease is the mechanical debridment, and removal of all the
factors that cause plaque accumulation.

There are some periodontal diseases in which the bacteria are not only in the plaque but
the bacteria are residing in the periodontal connective tissue, so in these cases the use of
chemotherapeutic agents is very important as an adjunctive to mechanical debridment.

Definitions:
Chemotherapeutic agent: is a general term for chemical substance that provides a
clinical therapeutic benefit.
The benefit comes from two things: the antimicrobial effect and from increasing the host's
defense, because the destruction in periodontal diseases come from bacterial toxins and
from the host defenses, so we have drugs that act on the bacteria and drugs that act on the
host defenses as we will see later in this lecture.

Antimicrobial agent: is a chemotherapeutic agent that works by reducing the number of

bacteria present

Antibiotics: are naturally occurring, semi synthetic or synthetic types of antimicrobial

agents that destroys (bactericidal) or inhibits the growth (bacteriostatic) of selective
microorganisms, generally at low concentration.

Antiseptics: are chemical antimicrobial agents that are applied topically or subgingivally
to mucous membranes, wounds, or intact dermal surfaces to destroy microorganisms and
inhibit their reproduction or metabolism and these could be Antiplaque, antigingivitis
mouth rinses or dentifrices (could be bactericidal as chlorhexidene or bacteiostatic).

Disinfectant: a sub category of antiseptic that are generally applied to inanimate surfaces
to destroy microorganisms that we use for disinfection of the clinic.

Chemotherapeutic agents:
We can use chemotherapeutic agents systemically or locally.

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Our chemotherapeutic agents to be effective they should reach the base of the periodontal
pocket, and this can happen either from the blood supply (systemic) or directly through a
syringe (local).

The systemic antimicrobial agents should be used in aggressive periodontitis especially

the localized.

The benefits of the use of local application of antimicrobial agents are:

• The high concentration of antimicrobial in the pocket that can decrease the
number of bacteria.
• This prevents the bacterial resistance.
• Reduce possible side effects.

Chemotherapeutic agents can have a dual mechanism of action: for example Tetracycline
can reduce collagen and bone destruction through it's ability to inhibit enzyme
collagenase.

When we talk about treatment of periodontal diseases we should keep these points in our
minds:

1. The treatment of periodontal diseases is based on the infectious nature of

these diseases

2. Ideally the causative microorganisms should be identified and the most

effective agent selected using antibiotic sensitivity test.

3. It is difficult to identify specific etiologic microorganism(s) rather than

microorganisms simply associated with various periodontal disorders, so there are
complex periodontal pathogens that cause the periodontal diseases, and no specific
antimicrobial can treat the disease so we need broad spectrum antimicrobial agents.

4. The possible clinical benefits of administrating antibiotics to help control

periodontal disease must be weighed against possible adverse reactions, so for serious
diseases the use of antimicrobial agents is very beneficial so we should give them to
the patients like in TB, but in some diseases the patient may not get benefits more than
the side effects so you should not give the patient antimicrobial in this case, like in
chronic periodontitis.

5. Common and indiscrement use of antibiotics worldwide has contributed to increasing

numbers of resistant bacterial strains over the last 15 to 20 years, due to continue wide
use antibiotics for cases that don’t need antibiotics.

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The characteristics of ideal antibiotic for use in
prevention and treatment of periodontal diseases:
• Specific for periodontal pathogens, but this can't be achieved in perio.
• Allogenic (doesn’t cause any allergy to the patient) and non toxic.
• Substantive, that means the drug is not absorbed but it is adsorbed
(‫ليس امتصاص لكن ادمصاص‬) that means the drug will reside in the tissues without
dissolving in the body fluids or the body structure, and when the concentration of the
drug is reduced in that area it comes again and substitutes its reduced concentration,
and this feature makes chlorhexidine very effective in perio treatment because it can
reside on the oral mucosa up to 12 hours that’s why we use it twice daily.
• Not in general use for treatment of other diseases and inexpensive.

The Ideal antibiotics for treatment of periodontal diseases does not exist, because as we
said not all the characteristics are achieved (not all the drugs are inexpensive, you can't
find drug that only acts in the periodontal tissues without affecting the other parts of the
body, etc...)

No single antibiotic at concentration achieved in body fluids inhibits all putative

periodontal pathogens, so sometimes we give combination of antibiotics because of the
complexity of pathogens, although the combination could lead to more side effects but the
disease is serious (aggressive periodontitis), it could lead to tooth loss or sometimes can
cause systemic problems.

Here the doctor punished us because our poor knowledge in the clinic, so study hard
students!!

Now look at the figure on the right

side:

This figure tells us about the treatment

of the different types of periodontal
diseases, if the person is healthy so he
should go for supportive periodontal
treatment (maintenance visits), but if he
is diagnosed with one of destructive
periodontal diseases like chronic
periodontitis, aggressive periodontitis,
chronic periodontitis as a manifestation
of systemic disease you should treat
him according to his disease.

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As you see in the figure if the disease is chronic periodontitis we should go for oral
hygiene, debridement, supportive treatment, and sometimes surgical access for root
debridment, but only antibiotic is indicated in cases where we have refractory sites (the
inflammation didn’t resolve from the sites of treatment after you finished the treatment of
the patient), after that if the disease didn’t resolve in this case the diagnosis could be
wrong from the beginning (it is not chronic it could be aggressive or chronic as a
manifestation of systemic disease) so it is very important to diagnose the disease properly
to know how to treat the patient.(the doctor said continue the figure by your self).

Antibiotics:
Here we will talk about specific types of antibiotics

Tetracyclines:

Why these drugs are widely used although these are bacteriostatic?
In tetracycline there are many good features but the most important feature is that this
drug can achieve the highest concentration in the gingival crivicular fluid (GCF) (2 to
4µg/ml), unlike the amoxicillin that doesn’t exist in the GCF but only you can detect it in
the serum.
So in tetracycline the drug reaches the base of the pocket from the serum and from the
GCF.

Other features:

• They have the ability to inhibit the growth of Actinobacillus

actinomycetumcomitans (Aa); this means that it is the drug of choice in the treatment
of localized aggressive periodontitis.
• They exert an anticollagenase effect that can inhibit tissue destruction, and we
will talk about this later.
• They may aid bone regeneration, and this is approved in some studies.

The doctor asked about the concentration of tetracycline hydrochloride and unfortunately no one
answered, and the doctor again punished us!!

The answer is 250mg, and it is given 4 times daily

Clinical use:

Again why tetracycline is the drug of choice as adjuncts in the treatment of localized
aggressive perodontitis?
Because it is very effective against Aa, and it is present in the GCF in high concentration.

It is not advisable to engage with a long term regimens of tetracyclines because of the
possible development of resistant bacterial strains.

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Tetracyclines now tend to be replaced by more effective combination antibiotics, because
we know that the complex bacterial pathogens of periodontal disease can't be eliminated
only by a bacteriostatic drug.

The less the times the patient take the drug the more the compliance, so the drug that is
taken once daily is better than the drug that is taken 4 times daily, so in tetracyclines we
prefer minocycline, and doxycycline.

Doxycycline:
Characteristics

1. Same spectrum of activity as minocycline.

2. its concentration is 100mg
3. Patients may be more compliant with doxycycline, because it can be taken once
daily.

Contraindications:

The doctor said this is very important but he didn’t say any thing about it.
But these are from the net:

• Nausea
• Diarrhea
• Vomiting
• Skin reaction to sunlight (photosensitivity)
• Upset stomach (dyspepsia)
• Loss of appetite
• Unexplained rash
• Difficulty swallowing (dysphagia).

The doctor said that it is very important to know when to take the drug before or after
meal, with or without milk, with or without falafel!! , but he didn’t say any thing.

The doctor means the precautions,

So these are the precautions as in the net:

• Doxycycline should not be administered together with milk, because it affects the
absorption, and the concentration in the blood.
• It should be taken on empty stomach 1 hour before or 2 hours after meals.
• pregnancy
• <8 years old
• avoid sun/UV light exposure
• caution if impaired renal fxn
• caution if impaired liver fxn
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 • caution if SLE
• caution if candidiasis predisposition
• caution in elderly pts

The regimen for the treatment of localized aggressive periodontitis is 100 mg twice daily
for the first day, then once daily for 20 days (the total is 21 days).

Metronidazole:
It is bactericidal broad spectrum and effective to anaerobic bacteria and all periodontal
pathogens are anaerobic, but it is not effective alone for the treatment of aggressive
periodontitis so we need combination of drugs to treat it.

It is effective against anaerobes such as Porphyromonas gingivalis and Provetella

intermedia

Clinical use:

1. Acute necrotizing ulcerative gingivitis.

2. Chronic periodontitis refractory on sensitivity test.
3. Aggressive periodontitis (in combination with amoxicillin).

It has been used:

• As a supplement to vigorous scaling and root planing, resulting in a significant

reduced need for surgery
• In combination with amoxicillin or amoxicillin - clavulanate potassium
(Augmentin), by this combination it may be of value in the management of patients
with localized aggressive periodontitis or refractory periodontitis

Contraindication:

1. It is contraindicated with alcohol ingestion, because it can result in sever cramp,

nausea, and vomiting (this is called Disulfiram like
reaction). Disulfiram reaction: This is an
unpleasant reaction due to the
2. Patients undergoing anticoagulant therapy should interaction of disulfiram and
avoid metronidazole because it prolong prothrombin alcohol. It can cause symptoms
such as flushing, throbbing in
time. head and neck, throbbing
3. It should be also avoided in patients who are
headache, breathing difficulty,
taking lithium (sedative). nausea, copious vomiting,
sweating, thirst, chest pain,
Others from the net: palpitations, tachycardia,
hypotension, syncope,
• Liver disease. uneasiness, weakness, vertigo,
• A stomach or intestinal disease such as Crohn's blurred vision and confusion.
disease.

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 • A blood cell disorder such as anemia (lack of red blood cells) or leukopenia (lack of
white blood cells).
• Epilepsy or other seizure disorder.
• Nerve disorders.

now look to the figure to the right:

In the periodontal disease we have loss of

attachment and what cause that loss are two
things:

1. the bacteria and their irritants (slight

role)
2. an inflammatory response from the host
cells toward the bacterial irritants which lead
to production of inflammatory mediators
such as PGE2, IL and matrix
metalloproteinase (MMP)

That leads to the bone and connective tissue destruction, which means 70% of destruction
is from the host defense and 30% of destruction is from the bacteria.

When we do scaling and root planning we are eliminating the first one which is the
bacteria, but some people thought about something that can inhibit the other effect which
is the host response.

This can be done by a drug that is called periostat.

Periostat:
It is systemic doxycycline hyclate in a concentration that does not have an antimicrobial
effect, and it only produce an anti-collagenase effect particularly that produced by
polymorphonuclear leukocytes to inhibit the host response.

It is available in 20mg but doxycycline that is antimicrobial it is 100mg, so periostat is

less in concentration than doxycycline, and this make the drug away from developing
resistance and away from developing side effects.

It is used twice daily, for at least 9 months, and its effect will last up to 2 years.

The end

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 ‫كلمات جميلة لبن القيم‬
‫)نسأل ال أن يرفع فى الجنة درجته (‬
‫من كتاب "الداء و الدواء"‬
‫يقول الشيخ ‪:‬‬
‫ال ‪-‬سبحانه وتعالىُ‪-‬‬
‫يعّوض عن كل ما سواه‪ ,‬ولُ يعّوض منه شيء‪,‬‬
‫وُ يغِني عن كل شيءولُ يغِني عنه شيء‪,‬‬
‫وُ ِيجير من كل شيء ولُ ِيجير منه شيء‪,‬‬
‫وَ يمنع من كل شيء‪ ,‬ولُ يمَنع منه شيء‪,‬‬
‫فكيف يستغني العبد عن طاعة من هذا شأنه طرفة عين?!‬
‫وكيف ينسى ذكره ويضيع أمره‬
‫حتى ينسيه نفسه‪ ,‬فيخسرها ويظلمها أعظم الظلم?!‬
‫فما ظلم العبد ربه ولكن ظلم نفسه‪,‬‬
‫وما ظلمه ربه ولكن هو الذي ظلم نفسه!‪.‬‬
‫وصلى الله وسلم وبارك على نبينا محمد وعلى آله وصحبه‬
‫والتابعين‬
‫إلى يوم الدين والحمد لله رب العالمين‬
‫أستغفر الله الذى ل إله إل هو و أتوب إليه‬

‫‪Done by: Khalid Feery‬‬

‫ل تنسونا من صالح دعائكم‪ ،‬وجزاكم ال كل خير‬

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