Adjunctive Use of Antimicrobials for Periodontal Disease by Dr.

Serraon
Perio exam 1 lecture 2

Fonts: control (reduce the number that the host response

From Lecture can manage).
From Book yung boxed parts, Lindhe
First we have pellicle, plaque formation,
Outline: coaggregation, biofilm, using up of oxygen,
1. Introduction predominance of anaerobes. They release
2. Chemical Plaque Control byproducts and endotoxins which can trigger a
a. Rationale response so we have now the acute inflammatory
b. Methods
i. Anti-adhesive
phase. Then there is Initial reaction of
ii. Antimicrobial vasoconstriction and vasodilation. And so knowing
iii. Plaque Removal this pattern, they come up with the rationale for
iv. Antipathogenic chemical control.
c. Vehicles for Chemical Agents
i. Oral Rinses
ii. Toothpastes The various periodontal diseases result from susceptible
iii. Irrigants hosts having their periodontal tissues colonized by specific
iv. Chewing Gums oral pathogens in numbers sufficient to overwhelm their
3. Chemical Agents for Plaque Control tissue defenses. Clinical success in the treatment of these
a. Antibiotics diseases thus requires reduction of the bacterial load or
b. Enzymes
the enhancement of the host tissues ability to defend or
c. Quaternary Ammonium Compounds
repair itself.
d. Phenols and Essential Oils
e. Natural Products Chemotherapeutic agent is a general term for a chemical
f. Fluorides substance that provides a clinical therapeutic benefit. This
g. Oxygenating Agents term does not specify in what way the agent aids in
h. Bisguanide Antiseptics attaining a clinical benefit. Clinical benefits can be derived
i. Chlorhexidine through antimicrobial actions or an increase in the hosts
j. Others resistance.
4. Antibiotics
An antimicrobial agent is a chemotherapeutic agent that
a. Penicillins
b. Tetracyclines
works by reducing the number of bacteria present.
c. Metronidazole Antibiotics are a naturally-occurring, semi-synthetic or
d. Other drugs synthetic type of antimicrobial agent that destroys or
- Cephalosporins inhibits the growth of selective microorganisms, generally
- Ciprofloxacin at low concentrations.
- Erythromycin Antiseptics are chemical antimicrobial agents that are
- Clindamycin
applied topically or subgingivally to mucous membranes,
wounds, or intact dermal surfaces to destroy
I. Introduction microorganisms and inhibit their reproduction or
metabolism. In dentistry, antiseptics are widely used as
Mechanical means of controlling plaque is not the active ingredient in antiplaque and antigingivitis
enough for some individuals. For whatever reason, mouthrinses and dentrifices.
there are individuals who find it hard to control Disinfectants, a subcategory of antiseptics, are
plaque by only mechanical means. So there are antimicrobial agents that are generally applied to
adjunctive techniques used like antimicrobials. The inanimate surfaces to destroy microorganisms.
human body is physical in nature (positive and Chemotherapeutic agents can be administered locally,
negative ions). The cell is composed of atoms, + and orally, or parenterally.
-, they use physics. Purpose: to reduce the number of bacteria present in the
diseased periodontal pocket.
Perhaps because of their lowered host response or Systemic antibiotics may be a necessary adjunct in
controlling bacterial infection because bacteria can invade
the pathogenicity of the bacteria, they cannot
periodontal tissues, making mechanical therapy alone
control plaque formation. Do you think you can
sometimes ineffective.
eliminate plaque in oral cavity? No. We have to
By Ken and Yssa Batch 2013
 Adjunctive Use of Antimicrobials for Periodontal Disease by Dr. Serraon
Perio exam 1 lecture 2

Local administration of antimicrobial agents, generally is the initial attachment of the primary plaque-
directly in the pocket, has the potential to provide greater forming bacteria)
concentrations directly to the infected area and reduce There is no biologically safe anti-adhesive
possible systemic side effects. agent that has been developed for dental use as
A single chemotherapeutic agent can have a dual of yet
mechanism of action. For instance, tetracycline is a 2. Antimicrobial agents
chemotherapeutic agent that can reduce collagen and
Examples are antiseptic, antibiotic
bone destruction through its ability to inhibit the enzyme
Kill bacteria when they are already attached to
collagenase. As an antibiotic agent, it also can reduce
periodontal pathogens in periodontal tissues. Additionally, the pellicle
tetracyclines have been shown to be effective when
administered systematically and applied locally. 3. Plaque removal agents
Are not antibacterial in nature
II. Chemical Plaque Control Disrupt dental plaque so it will not form,
mouthwashes (e.g. colgateplax)
A. Rationale for chemical control
4. Antipathogenic agent
They lower the pathogenicity of the bacteria
- To compensate for inherent inadequacies of
It does not merely remove the bacteria
mechanical plaque control
o Tooth brushing (alone: not
C. Vehicles for chemical agents
sufficiently efficient)
o Patients are lacking in skill when it
1. Oral rinses
comes to brushing adjuncts are
Most are formulated only to address halitosis
necessary
2. Toothpaste
o Plus the bristles of the toothbrush are
There is no astringent effect if you dont put
not able to reach certain areas of the toothpaste in the brush. We are given false
teeth (grooves and deep fissures) and security. When toothpaste war started, people
of the gums became aware tartar
- To augment plaque control for high
risk/susceptible individuals 3. Irrigants
o Individuals who are at HIGH RISK are Only remove debris, with little effect on plaque
those that have diseases which are deposits
associated with periodontal disease.
o Individuals with high caries index, Expensive. These come in spray or solution
those who smoke, and those who are
pregnant are considered 4. Chewing gums
SUSCEPTIBLE. Xylitol or sometimes chlorhexidine is put in
chewing gums
o We have to augment by chemical
Incorporating chemical agents and
means.
encouraging people to chew can be used as a
vehicle for introducing chemical agents. It can
B. Methods of supragingival chemical plaque control also increase saliva production, which is a
natural defense
1. Antiadhesive agents Can reduce occlusal plaque deposits
prevents bacteria from adhering to pellicle,
stops the first stage of plaque formation (which 5. Varnishes
Can be used to deliver chlorhexidine
By Ken and Yssa Batch 2013
 Adjunctive Use of Antimicrobials for Periodontal Disease by Dr. Serraon
Perio exam 1 lecture 2

Topically applied chemical agents o Used as an antiseptic mouth rinse

at 0.5 % concentration, with
III. Use of chemical agents for plaque control substantivity of 3-5 hrs
For Prolonged retention on oral surfaces o Monocationic
Since we use this in oral cavity, we hope that o More readily absorbed than
there is prolonged retention on oral surfaces, to chlorhexidine
oral structures (gingival, tongue even plaque).
So the action is also prolonged
4. Phenols and Essential oils
For Maintenance of antimicrobial action
a. Thymol, eucalyptol, menthol and
There is a tendency that the action can
methyl salicylate (may also contain
diminish because when we talk, we salivate.
alcohol)
For Slow neutralization
b. Triclosan is considered as phenol group
Chemical Agents for Plaque Control o at 0.2% concentration has
1. Antibiotics moderate plaque inhibition action
Risk to benefit ratio is high and 5hrs substantivity.
There is a high possibility of allergic reaction. It Increasing the concentration will
can also induce the microorganisms to mutate no longer provide benefit
so that they can withstand the antibiotics (determined through research)
therefore developing resistance. o Action is enhanced by addition of
Not recommended zinc citrate or copolymer,
2. Enzymes polyvinylmethyl ether, maleic acid
a. First group plaque removal agents (first used in industries before
o Have the potential to disrupt the early used in dentistry, just in higher
concentration)
plaque matrix thereby dislodging
bacteria from the tooth surface
5. Natural products
o Dextranases, mutanases and
a. Herb and plant extracts
proteases
(sanguinarine)
o Can be found in plaque. They destroy
Trying to extract what we have
the dental plaque and trying to see if there is use in
b. Second group enhances host defense dentistry
o Glucose oxidases and o In use for centuries
amyloglucosidases o Zinc salt are incorporated to
o Catalyse conversion of thiocyanate enhance the effects, but benefit-
and hypothicyanate with cost ratio may be low
o inhibits oral bacteria Mostly it is triclosan that is used
(hypothiocyanate destroys the today
cellular wall) Recently associated with precancerous
oral lesions (usually the reason for this is
3. Quaternary ammonium Compounds the alcohol product it contains)
- Side effects include teeth staining (this is not a
disease but a side effect) 6. Fluorides
a. Benzylconium chloride Caries preventive benefits
b. Cetylpyridinium chloride Amine fluoride and stannous fluoride
show some plaque inhibitory activity
By Ken and Yssa Batch 2013
 Adjunctive Use of Antimicrobials for Periodontal Disease by Dr. Serraon
Perio exam 1 lecture 2
It is difficult to fluoridate our source of
drinking water because in provinces, we have
deep well as a source. There are also 7,107
islands. There would be different fluoride
contents in the water. Colgate have different
ppm of fluoride depending on where it is
distributed
7. Oxygenating agents
Hydrogen peroxide has been in use for
supragingival plaque control
o It is used to mechanically wash off plaque
easier
o It comes in powder form that is mixed with
water.
o There will be decreased oxygen need so
no anaerobes
o However, it masks the perio condition of
gingival inflammation so it is not used.
o It is helpful in the detection of the presence
of abscess that can aggravate the
periodontal disease condition
when you see an enlargement, you
have to check first and find out if there
is pus
Peroxybate has been in use to treat acute
ulcerative gingivitis
8. Bisguanide antiseptics
Clorhexidine = considered today as the
golden standard for oral rinses
Available in 3 forms; digluconate, acetate,
and hydrochloride salts
Study by Loe and Shiott (1970) showed
that rinsing with 10 ml of 0.2%
chlorhexidine gluconate inhibited plaque
regrowth and gingivitis
Digluconate = used in oral rinses
Prevents plaque from reforming
Optimum concentration: 0.2%
Others: alexidine and octenidine
MOA
1. potent antibacterial (leakage of
intracellular components and precipitation of
bacterila cytoplasm leading to cell death)
By Ken and Yssa
2. readily adsorbs to surfaces including
pellicle coated teeth
3. persistent bacteriostatic action (>12hrs)
9. Chlorhexidine
o Chlorhexidine has a substantivity of 10-
12 hrs main advantage
Chlorhexidine products
o Oral rinses, gel, sprays, toothpaste, varnishes
(paint/ topically applied to tooth surfaces)
Side effects
o Teeth staining (clinically appears like
tobacco stains)
o Taste alterations (destroys taste buds)
o Parotid swelling (clinically appears like
parotitis)
o Oral mucosal erosions (idiosyncratic
reaction)
o Favors supragingival calculus formation
(but this kind does not induce gingival
inflammation. The problem is when you stop
using it)
o Bitter taste
Clinical applications
o As an adjunct to oral hygiene and
professional prophylaxis
(before undergoing periodontal therapy [root
planning, surgical and non surgical], we usually
prescribe oral rinses because patients usually
will not brush the area that is affected.
Sometimes they are also advised so that there is
continual healing on those areas)
o Post surgical rinse
(part of the chain of asepsis)
o Patients with jaw fixation
(if the muscle movement will tend to pull the
part of the fracture, they will open that part so
they need chlorhexidine for prophy)
Clinical Applications
o Adjunct for handicapped
(stroke patients, mental deficiencies)
o Medically compromised patients
predisposed to oral infections
Batch 2013
 Adjunctive Use of Antimicrobials for Periodontal Disease by Dr. Serraon
Perio exam 1 lecture 2
(there should be a continuum of oral health
because people who are confined in the hospital
tend to stop oh practices)
o High risk caries patients
o Removable and fixed oral appliances
o Oral ulcerations (they have the tendency not
to brush)
o Denture stomatitis
2. Other antiseptics
Sodium lauryl sulfate
Povidone iodine 1% (60 min
substantivity)
Hexetidine 0.1 % or bactidol
(limited plaque inhibitory and
antiplaque activity)
I. Adjunctive use of antibiotics
periodontitis
Understanding periodontal infection
o There are bacteria that are not susceptible
to antimicrobial and antibacterial agents.
If the main effector is removed, which is
plaque, the periodontal infection will not
progress.
o Some respond to mechanical control but
some also do not. So we resort to
antibiotics.
Limitation of mechanical therapy
o Sometimes, theres nothing much we can
do if the host response is weak and it is also
genetically determined
Certain lesions does not respond to cause
related therapy
Certain bacterial strains present high
pathogenicity (AA)
Increases resistance and risk benefit ratio
is high.
Drug delivery routes
1. Systemic route (orally, parenterally, IV)
Advantages
o Wide distribution
o May reach deep areas (since it is
delivered to the blood supply, it can
By Ken and Yssa
reach areas which are not
accessible. It is distributed to the
general circulation then it can
reach the gingival pockets
o Proplonged action
o Easy to administer
Disadvantages
o Lesser drug concentration will
reach the target area
o Systemic side effects
(upset stomach,anaphylactic reaction)
o Patient compliance
(because its not part of their daily life
so they tend to forget it, there will be
no continuity in the blood level)
Local delivery system
2. Local Delivery System
in Advantage
o high dose at treated site
o little side effects
Disadvantage
o Lesser drug concentration will
reach the target area
o May not reach other sites (deep
sites)
o Washing effect of crevicular fluid
may lessen the effect
o Tedious for the clinician
(you have to remind patients
everytime)
Antibiotic of Choice
Then drug must show in vitro effect against
targeted microorganism
It should show that sufficient dose can be
reached without adverse effect
It should have a practical advantage over the
conventional therapy
An ideal antibiotic for use in prevention and treatment of
periodontal diseases should be specific for periodontal
pathogens, allogenic and nontoxic, substantive, not in general use
for treatment of other diseases, and inexpensive.
Currently, an ideal antibiotic for the treatment of periodontal
diseases does not exist. XD
Although oral bacteria are susceptible to many antibiotics, no
single antibiotic at concentrations achieved in body fluids inhibits
Batch 2013
 Adjunctive Use of Antimicrobials for Periodontal Disease by Dr. Serraon
Perio exam 1 lecture 2
all putative periodontal pathogens. Indeed, a combination of
antibiotics may be necessary to eliminate all putative pathogens
from some periodontal pockets.
1. Penicillins
Inhibit bacterial cell wall synthesis
May induce allergic reactions (up to 10%
of patients may be allergic to penicillin)
and bacterial resistance
Amoxicillin and amoxicillin clavulanate
(Augmentin) are the most commonly
used for periodontal infections
Bacteriostatic but commonly show high
conc in gig crev fluid than in serum and
neutralizes collagenase
Adverse reaction is staining and
gastrointestinal upset (tetra, minocycline
and dioxycyxline)
Penicillins are the drugs of choice for the treatment of many
serious infections in humans and are the most widely used
antibiotics. They inhibit bacterial cell wall production and
therefore are bactericidal.
Amoxicillin is a semisynthetic penicillin with an extended
antimicrobial spectrum that includes gram positive and gram
negative bacteria. It demonstrates excellent absorption after oral
administration. Amoxicillin is susceptible to penicillinase, a beta
lactamase produced by certain bacteria that breaks the penicillin
ring structure and thereby renders penicillins ineffective.
Amoxicillin may be useful in the management of patients with
aggressive periodontitis, both in the localized and generalized
forms. Recommended dosage is 500 mg tid for 8 days.
Amoxicillin-Clavulanate (Augmentin) is the combination of
amoxicillin with clavulanate potassium. It is resistant to
penicillinase enzymes produced by some bacteria. Augmentin
may be useful in the management of patients with refractory or
localized aggressive periodontitis.
2. Tetracycline
Bacteriostatic but commonly shows higher
concentration in the gingival crevice than in
serum and neutralizes collagenase
It should be shown that sufficient dose can be
reached without adverse effect
It should have a practical advantage over the
conventional therapy
3. Metronidazole
By Ken and Yssa
Bactericidal against anaerobes disrupting
DNA synthesis (for LBM sot)
Adverse effect prolongs prothrombin time
Usually in combination with amoxicillin
Metronidazole has been used clinically to
treat
Gingivitis
Acute Necrotizing Ulcerative Gingivitis
(successful?)
Chronic Periodontitis
Aggressive Periodontitis
Metronidazole is bactericidal to anaerobic organisms and is
believed to disrupt bacterial DNA synthesis in conditions in
which a low reduction potential is present. It is not the drug of
choice for treating A. Actinomycetemcomitans infections, but it
may be effective at therapeutic levels owing to its hydroxyl
metabolite. However, it is effective against AA when used in
combination with other antibiotics. Metronidazole is also
effective against anaerobes such as PG and PI.
Metronidazole used as a supplement to rigorous scaling and root
planning resulted in a significantly reduced need for surgery
when compared with root planning alone.
Other drugs
Narrow-spectrum antimicrobials include penicillin, amoxicillin,
cephalexin, the macrolides (erythromycin, clarithromycin, and
azithromycin), and the tetracyclines (including doxycycline).
Broad-spectrum antimicrobials include clindamycin; the combination of
a penicillin (ie, amoxicillin) plus a beta-lactamase inhibitor (ie
clavulanate); and the combination of metronidazole plus penicillin,
amoxicillin, or a macrolide. These possess a broad spectrum of activity
against most odontogenic pathogens, including aerobic and anaerobic
beta-lactamase producers. Furthermore, some agents (eg, clindamycin
and amoxicillin-clavulanate) provide better pharmacokinetic and
pharmacodynamic properties against the odontogenic pathogens
compared with the others
Cephalosporins
Resistant to a number of beta lactamases
normally active against penicillin
Generally not used to treat dental-related
infections. The penicillins are superior to
cephalosporins in their range of action
against periodontopathic bacteria
Side effects: allergy, urticaria, fever,
gastrointestinal upset
Ciprofloxacin
Batch 2013
 Adjunctive Use of Antimicrobials for Periodontal Disease by Dr. Serraon
Perio exam 1 lecture 2
A quinolone active against gram-negative
rods, including all facultative and some
anaerobic putative periodontal pathogens
Because it demonstrates minimal effect on
Streptococcus species, which are associated
with periodontal health, ciprofloxacin
therapy may facilitate the establishment of a
microflora associated with periodontal
health.
At present, it is the only antibiotic in
periodontal therapy to which all strains of AA
are susceptible. It also has been used in
combination with metronidazole.
Side effects: nausea, headache, abdominal
discomfort
Erythromycin
Is a macrolide (which inhibits protein
synthesis and can be bacteriostatic or
bactericidal, depending on the concentration
of the drug and the nature of the
microorganism)
Erythromycin does not concentrate in
gingival crevicular fluid, and it is not effective
against most putative periodontal pathogens.
Not recommended as an adjunct to
periodontal therapy
Clindamycin
Most bacteria develop resistance to penicillin
so they use cephalosporins
Clindamycin is effective against anaerobic
bacteria. It is effective in situations in which
the patient is allergic to penicillin.
Clindamycin has shown efficacy in patients
with periodontitis refractory to tetracycline
therapy.
Side effects: associated with
pseudomembranous colitis (diarrhea,
cramping)
Chronic periodontitis
Generally adjunctive antibitotic therapy is not
recommended because it is not usually
systemic
There is what we call the active stage, then
we can give antibiotics
By Ken and Yssa
Applied only in advanced cases and those
undergoing active burst period
How to determine if there is a burst?
Refractory periodontitis and rapidly progressing
periodontitis
Despite Perio Tx, the prognosis is poor.
Adjunctive use of antibiotics can be helpful
Tetracycline seems to show beneficial effects
Tetracyclines 250mg qid 2-3wks
Minocycline 100mg bid 2-3 wks
Doxycycline 200mg loading dose, 100 mg
once a day for 2-3 wks
Early onset periodontitis
Combination drug
Amoxicillin 250mg mg tid and metronidazole
250 mg tid for 7 days
Locally delivered Antimicrobials
1. Actisite tetracycline containing fibers
2. Stridox gel system containing doxycycline
3. Periocycline gel suspension containing
minocycline
4. periochip biodegradable gelatin matrix containing
chlorhexidine
Conclusions
1. Most cases of periodontitis responds to mechanical
therapy
2. Adjunctive use of antimicrobials maybe justified
for early onset ang aggressive types of periodontitis
3. Localized non-responding or recurring sites can be
treated by local delivery system
Host response Therapeutics
Strategy of trying to modify inflammatory
response of the host (destruction of tissues
may be attributed to host response, so some
researchers advocate : what if we change the
host reponse?)
3 Categories of Host Modulating Agents
1. Antiproteinases (e.g. tetracycline, it can destroy
collagenase)
Matrix metalloproteinases
Batch 2013
 Adjunctive Use of Antimicrobials for Periodontal Disease by Dr. Serraon
Perio exam 1 lecture 2

2. Anti-inflammatory drugs (NSAIDS, pain reliever)
PGE2, bone destruction, what
if we can reduce the amount
of prostaglandin? So we can
decrease bone destruction so
they use NSAID
3. Bone sparing drugs (bisphosphonates)
Osteoporosis and Pagets
disesase
Osteoclasts act on tehm
instead of osteoblasts
Binds with hydroxyapatite crystals to prevent
dissolution by interfering with osteoclast
formation
High risk of jaw osteonecrosis
New directions
Disruption of cell signaling pathways
Protein antagonist strategies
Tumor necrosis factor antagonist

Antiproteinases
Role of MMP (collagenase, gelatinases at
metalloelastase) in periodontal disease
Tetracycline (1985) have anticollagenolytic
activity. Doxycycline (20 mg bid)
Hellow.
For comments and suggestions pls text me.
Aw, namimiss ko si Jihim, Boy, Mami Den, Bran and Ian dito sa Tanay. Haha. Antok
na si bes. Happy studying guys. Try naming matapos tom yung last lec para makapag
aral na kayo. Nice job transers!
-ken

Anti inflammatory drugs (NSAIDS)

Role of PGE2 in periodontal disease

NSAIDS prevents prostanoid formation
through inhibition of cyclooxygenase

- May be of therapeutic value in treating

periodontal disease because of their ability to
interfere with arachidonic acid metabolism
and thereby inhibit the inflammatory process
- Some NSAIDs have been shown to affect the
response of polymorphonuclear neutrophils
(PMNs) to inflammation not related to
prostaglandin inhibition

- Flurbiprofen appears to be an NSAID worthy

of further investigation because:
o It inhibits PMN migration
o It reduces vascular permeability
o It inhibits platelet aggregation by
inhibiting cyclooxygenase

Bonesparing drugs
Biphosphonate drugs similar to
pyrophosphate (component of metabolism)

By Ken and Yssa Batch 2013