Melissa Fellman, RDH, BS

Pharmacology and Periodontal Disease:

Implications and Future Options
Introduction There are many systemic antibiotics on the market. The most
Periodontal disease is a complex inflammatory disease characterized commonly used include tetracycline, ciprofloxacin, metronidazole and
by bacterial infection, host response and patient behavior. The debride- the penicillins, including amoxicillin and amoxicillin/clavulanate acid
ment of plaque biofilm and adequate home care are essential (Augmentin®). Tetracycline is bacteriostatic, targets both gram
elements of a patient’s periodontal treatment. Antibiotics, antimi- positive and gram negative organisms, and has become bacterial
crobials, herbs, antivirals and vaccines may also be beneficial when resistant. Ciprofloxacin is bactericidal, targets gram negative rods, and
combined with scaling and root planing. There is research both in may cause gastrointestinal discomfort. Amoxicillin and Augmentin are
support of and against the use of supplemental therapy to traditional both bactericidal, with Augmentin targeting a more narrow spectrum
biofilm removal.1 When considering the use of adjunctive therapy it than amoxicillin. Augmentin was developed due to amoxicillin’s bacte-
is always important to do a detailed medical health history with your rial resistance from penicillinase enzyme sensitivity.1
patient to rule out any known contraindications. Of the many systemic antibiotics available, there is no consensus as to
an ideal dose and duration. The choice of antibiotic should be made on
Antibiotics an individual basis. In addition to serious adverse effects, like anaphy-
The physical removal of biofilm has proven to be the most effective lactic shock, microbial resistance is a growing concern.4 Other issues
method for treating periodontal disease. The use of adjunctive antibiotic with oral antibiotic administration are patient adherence and adequate
therapy, either systemic or topical, is controversial. Some studies show absorption from the gastrointestinal tract.
superior results with antibiotic use while others show no clinical differ- Understanding that the periodontal disease process may be initi-
ence. There is a general consensus that antibiotics should not be used ated by bacteria but the individual’s host response was critical to the
as a monotherapy in the treatment of periodontal disease. Antibiotics progression of this disease led to the FDA approval of doxycycline at a
as a stand-alone treatment are ineffective at diminishing intact subgin- sub-antimicrobial dose (20mg twice daily). When administered
gival biofilms.2 at this low dose, doxycycline does not cause the long term side
The American Academy of Periodontology has offered guidelines for effects seen with other systemic antibiotics. Randomized double blind
systemic and topical antibiotic use in treating periodontal disease.3 placebo controlled trials demonstrated reduction in probing depths,
These guidelines suggest that aggressive types of periodontitis and improvement in clinical attachment levels and decreased bleeding on
acute periodontal infections should be treated with systemic anti- probing when used as an adjunct with scaling and root planing.5
biotics while chronic infections should be treated with topical therapy.
A recent review evaluating non-surgical chemotherapeutic strategies
Antibiotic therapy is generally used as a follow up treatment after for the management of periodontal disease determined that “systemic
conventional mechanical therapy. Aggressive periodontitis may use antibiotics reach the periodontal tissues by transuduction across
systemic antibiotics as an adjunctive therapy. serum, then cross the crevicular and junctional epithelia to enter the
gingival sulcus.”1 By the time the systemic antibiotic reaches
Classification of Antibiotic Agents That Can Affect Periodontal Microbes the gingival sulcus it no longer has an adequate concentra-
BACTERICIDAL BACTERIOSTATIC tion to achieve the desired antimicrobial effect. This supports
the fact that the mechanical disruption of biofilm must be
Cephalosporins (Includes Keflex®, Ceclor®) Clindamycin*
included in the treatment of periodontal disease.
Macrolides* (Includes Erythromycin, Macrolides* (Includes Erythromycin,
Azithromycin, Clarithromycin) Azithromycin, Clarithromycin) Topical Antibiotic Therapy
Metronidazole Tetracyclines (Includes Doxycycline, Minocycline)
Topical (local) antibiotic/antimicrobial therapy (LAA) was
Penicillins (Includes Ampicillin, Amoxicillin, the natural progression from systemic administration. It
Augmentin®, Penicillin VK)
was thought that LAAs would solve the risk to benefit ratio
Quinolones (Includes Ciprofloxacin) of systemic antibiotics.5 Although there are some studies
*Bactericidal against some organisms at high blood levels supporting the use of topicals, most fail to demonstrate a
Table modified from: Haveles, E. B. (2011). Applied Pharmacology for the Dental Hygienist. (6th ed.). significant difference between scaling and root planing alone.
Maryland Heights, MO: Mosby Elsevier, p. 77-78.
Continued on Page 10

CDHA Journal – Summer 2010 9

Investigations do show benefits for high risk patients, such as smokers,
who do not respond to mechanical therapy.6-7 Recent studies have
demonstrated that the use of LAAs resulted in an overall reduction of
the bacterial bioburden with reduced cardiovascular event risks.8-9
The first locally administered antibiotic for periodontal disease was
Actisite®, made up of nonabsorbable fibers filled with tetracycline.
Although Actisite was found to be effective in many cases, placement
and patient follow-up for fiber removal were challenging issues.1 A
bioabsorbable local delivery device called PerioChip® was then deve-
loped. It was comprised of 34% chlorhexidine gluconate, about 5mm
round and 1mm thick. It is the only LAA that is not an antibiotic.
Atridox® is a 10% doxycyline hyclate gel and is prepared by mixing
powder and liquid from two syringes. The antibiotic is administered
into the gingival sulcus through a cannula. Absorption lasts up to 21
days, while therapeutic drug levels in the gingival crevicular fluid start
to decline at 7 days. The most notable drawback is the high level of
clinician skill needed to deliver this therapy as the material tends to
come out of the pocket as the syringe is being pulled out of the sulcus.
The majority of the time, more than one site can be treated depending
on the depth and size of the pockets.1
Arestin® is comprised of spheres embedded with 2% minocycline HCl
that is slowly released and holds the therapeutic dose in the gingival
crivicular fluid for 14-21 days. The most notable drawback for Arestin
is the delivery dose. The syringe holds pre-set doses that may not
be sufficient for every site. This results in the need to reapply in the
same pocket.
Currently, resorbable antibiotics such as Atridox® and Arestin® are the
topical antibiotics of choice. The American Academy of Periodontology
(AAP) supports that local adjuncts, when compared with scaling and
root planing alone, provide limited improvement.10 Locally admin-
istered antibiotics still require a strict health history review to verify
there are no known allergies. Even though these medications are
applied topically, as opposed to oral administration, the same
precautions apply.
Antibiotic Brand Name Delivery Absorption
10% Doxycyline Atridox® Fluid mixed in a 21 days
syringe, Multisite
2% Minocycline Arestin® Solid dose applies 14-21 days
HCl microspheres with a syringe,
Single site
Antiseptics
Unlike topical controlled-released antibiotics, oral rinses do not
penetrate deep into the gingival sulcus. Despite this limitation they do
show benefit when used adjunctively for gingival inflammation. Oral
rinses are also of great value in post surgical healing. Substantivity is
a crucial component when considering the effectiveness of a mouth
10 CDHA Journal Vol. 25 No. 2
rinse. This term refers to the adherent qualities of a mouthwash and its
ability to be retained. Saliva has a natural flushing property making it
difficult to maintain an antimicrobial effect. Research shows a signifi-
cant antibacterial effect up to 7 hours after mouthrinses with high a
substantivity property.11
First generation antimicrobials include phenolic, sanguinarine, qua-
ternary compounds. Listerine® and its generics are phenolics which
possess the only ADA Seal of Acceptance among the first generation
antimicrobials. Listerine contains 26.9% alcohol, alters the bacterial
cell wall, and has 36% gingivitis reduction.1 Cepacol® and Scope®,
quaternary ammonium compounds, contain 14% and 18.9% alcohol
respectively, increase bacterial cell wall permeability causing cell lysis,
and reduces gingivitis approximately 15%.1
Second generation antimicrobials include cetylpyridinium chloride
(CPC) and chlorhexidine (CHX). A commercial name for CPC is Crest®
Pro-Health®, which contains 0.07% CPC. Bacteria cells are killed by
cellular pressure, resulting in a similar efficacy as Listerine. Chlorhexi-
dine has many commercial products including the availability of a
nonalcoholic version by Sunstar Americas, Inc. Peridex® by 3M Espe
and Periogard® by Colgate® Professional are two examples of popular
chlorhexidine-based products. Their active ingredient is 0.12%
chlorhexidine. Cell death results from altered osmotic equilibrium.
CHX efficacy in the reduction of certain aerobic and anaerobic bacteria
has been shown to be as high as 97% after 6 months of use. CHX
has 29% gingivitis reduction. The gingivitis reduction percents listed
above for both first and second generation antimicrobials are based on
efficacy data published by manufacturers.1
Other antimicrobials include oxygenating, chlorine dioxide, and zinc
chloride agents. Peroxyl® is an oxygenating agent with the active
ingredient of hydrogen peroxide. It has anti-inflammatory properties
as well as a bubbling action to clean and alleviate discomfort. Short
term studies have produced controversial findings. Oxyfresh®, a 1%
chlorine dioxide agent, has minimal plaque reduction. It is a stable,
free radical and an oxidant with algicidal, bactericidal, cysticidal,
fungicidal, sporicidal, and viricidal properties. Oxyfresh is primarily
used for the treatment of halitosis. Breath Rx® is a zinc chloride agent
designed to odorize sulfhydryl groups with zinc ions. It claims to be a
scientific bad breath treatment specifically designed to help treat the
causes of bad breath and the symptoms.1
Antimicrobial mouth rinses have been linked to several side effects;
some more serious than others. First generation compounds like
Listerine can cause a burning sensation and bitter taste. Chlorhexidine
can cause supragingival calculus build-up and staining. Research
has demonstrated permanent damage to enamel through erosive pH
levels and abrasive antimicrobial toothpastes.1 Carcinogenic changes
have been linked to the use of oxygenating agents and mouth rinses
containing alcohol.1
Nutraceuticals
As antibiotic resistance becomes more of a concern, health care pro-
viders looking for alternate adjunctive periodontal therapies for their
patients. Some examples of nutraceuticals include herbal and nutri-
tional supplements and the future of this type of therapy is promising.
There are approximately 500,000 plant species, with only 1% having
been photochemically investigated. Herbal plant extracts have been
shown to reduce the level of biofilms influencing the level of bacterial
adhesion. This has shown results with the reduction of periodontal
disease. Some herbs such as Coptidis rhizome extract and Hamamelis
virginiana, are used as bactericidal agents against oral bacteria while
others such as cranberry, Polygonum cuspidatum and Mikania are
used to inhibit adhesion.12
The use of probiotics in the control of periodontal pathogens is emerg-
ing. Probiotics are “live microorganisms, which when administered
in adequate amounts confer a health benefit on the host.”13 Simply
put, they are healthy bacteria that displace unhealthy or pathogenic
bacteria. A reduction in gingivitis and dental plaque has been shown
with the administration of L. reuteri Prodentis® gum chewed twice
daily in patients with moderate to severe gingivitis.14 GUM® PerioBal-
ance®, marketed by Sunstar Americas, is a once daily lozenge with
L. reuteri Prodentis® that claims a reduction in moderate to severe
plaque and bad breath.15 EvoraPlus™ from Oragenics, Inc. is another
new probiotic for oral health and is used once daily. This supplement
contains a combination of three bacterial strains Streptococcus uberis
KJ2, S. oralis KJ3, and S. rattus JH145, and claims a reduction in
periopathogens within the periodontal pocket.16
Antivirals
A new area of research when evaluating periodontal disease is the use
of antivirals. The Epstein-Barr (EBV) virus has been associated with
recurrent periodontal disease. Since bacterial disease may be second-
ary to viral infections, antiviral treatment decreases EBV and improves
the periodontal condition.17 The Human Cytomegalovirus (HCMV) has
also been linked to periodontal disease. The HCMV can cause infections
in immune-compromised individuals like organ transplant patients or
patients with acquired immune deficiency syndrome (AIDS). Periodon-
tal lesions can exhibit great amounts of EBV and HCMV. Anti-herpes-
virus chemotherapy can decrease salivary viral loads resulting in the
improvement if secondary bacterial periodontal infections exist.18
Vaccines
Vaccine therapy in the fight against periodontal disease is also a new
and exciting option. As discussed earlier, antibiotic resistance is a
growing worldwide problem. Vaccines offer a solution to the overuse of
antibiotics in dentistry. Vaccine development is based on the identifica-
tion of virulence factors that stimulate the induction of salivary
immunoglobulin A antibody response. When used for periodontal
disease, Porphyromonas gingivalis and Aggregatibacter actinobacillus
CDHA Journal – Summer 2010 11
have been identified as antigenic targets.19 More research is needed in
this field before it is widely accepted as an alternative to antibiotic or
antimicrobial therapy.
Conclusion
All drug sensitivities and allergies should be reviewed prior to incorpo-
rating pharmacological agents into a patient’s treatment regimen. The
future is promising in the areas of nutraceuticals and vaccines but more
research is needed. The future of public health can be greatly affected
by the scientific breakthroughs becoming made in dentistry. Long time
traditional regimens of antibiotics and antimicrobials have served
our profession well and assisted hygienists to achieve optimal patient
results.
About the Author
Melissa Fellman, RDH, BS, is the Program
Coordinator and Evaluation Specialist for the
Nevada State Oral Health Program. In addi-
tion, she is an instructor in the dental hygiene
program at Truckee Meadows Community College
(TMCC) in Reno, NV where she teaches pharma-
cology. Melissa is in the process of completing a
Master’s degree in public health at the University
of Nevada, Reno where her graduate research includes conducting a
dental hygiene needs assessment on HIV outpatients and developing a
coalition to increase access to dental hygiene care for HIV positive indi-
viduals in northern NV. Melissa can be reached at mfellman@tmcc.edu
References
1. Krayer JW, Leite RS, Kirkwood KL. Non-surgical chemotherapeutic treatment
strategies for the management of periodontal diseases. Dent Clin N Am. 2010;
54: 13-33.
2. Schaudinn C, Gorur A, Keller D, Sedghizadeh PP, Costerton JW. Periodontitis:
an archetypical biofilm disease. JADA. 2009;140: 978-86.
3. The American Academy of Periodontology (AAP). J. Periodontol. 2004;75: 1553-65.
4. Heitz-Mayfield LJA. Systemic antibiotics in periodontal therapy. Aus Dent J.
2009;54(1 Suppl): S96-S101.
5. Cortelli JR, Aquino DR, Cortillo SC, Carvalho-Filho J, Roman-Torres CVG, Costa
FO. A double-blinded randomized clinical trial of subgingival minocycline for
chronic periodontitis. J Oral Sci. 2009;50(3): 259-65.
6. Goodson JM, Gunsolley JC, Grossi SG, Bland PS, Otomo-Corgel J, Doherty F,
Comiskey J. Minocycline HCl microspheres reduce red-complex bacteria in
periodontal disease therapy. J Periodontol. 2007;78: 1568-79.
7. Machion L, Andia DC, Lecio G, Nociti FH Jr, Casati MZ, Sallum AW, Sallum EA.
Locally delivered doxycylcline as an adjunctive therapy to scaling and root
planing in the treatment of smokers: a two-year follow-up. J Periodontol.
2006;77(4): 606-13.
8. D’Aiuto F, Parkar M, Nibali L, Suvan J, Lessem J, Tonetti MS. Periodontal infections
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randomized controlled clinical trial. Am Heart J. 2006;151(5): 977-84.
References continued on Page 25
 CareerCorner
What is the most exciting aspect of your work?
Traveling and teaching hands-on advanced periodontal instrumen-
tation courses around the world. Basic instrumentation skills and
ultrasonic instrumentation are taught and practiced everywhere but
there are very few teachers or practitioners who have ever been
able to take an advanced course that focuses on access, adaptation
and scaling of difficult problem areas such as deep distal or palatal
pockets, line angles and furcations. When I teach the advanced
instrumentation course, the rapid improvement and gratitude of
these clinicians is extremely rewarding and renews my resolve to
keep on traveling and teaching.
What do you believe our profession should know about mentation workshops throughout the U.S. and abroad. In 2005, she
periodontal disease in 2010?
Regardless of adjunctive antimicrobial therapies such as local
delivery antibiotics, subgingival irrigation or lasers, the keystone of
good periodontal therapy still is, and has always been, thorough
debridement of calculus and biofilm. Looking for a fast, easy way
out and shifting the focus away from meticulous root debridement
is a dangerous path. Dental hygienists, who lose their focus and do
not develop advanced skills, run the risk of losing their positions to
lesser educated individuals.
I have heard some dentists say, “I can teach a monkey to scale.”
After 40 years of teaching dental and dental hygiene students, I
know that I can teach any student to gross scale with an ultrasonic
scaler and place Arestin® in a short period of time. However, I can
only teach a small number of students to be very highly skilled
at advanced periodontal scaling and root planing. Our profession
needs to be recognized for special knowledge and exceptional skills
that are not easily acquired. activity against oral bacteria: potential application in the prevention and
Periodontal disease is not simple and it is not easy to treat
effectively. Excellent treatment requires intensive initial therapy and
constant vigilance during a lifetime of maintenance. Hygienists who
oversimplify periodontal treatment do a great disservice to their
patients and to the dental hygiene profession as a whole.
Please share a memorable experience from your bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri.
professional career.
From 1973 to 1975, I shared an office and taught dental students
with Dr. Esther Wilkins at the Tufts School of Dental Medicine in
Boston. What an experience to be able to teach with and assist the
“Guru” of Dental Hygiene! We worked together so well that we
developed a deep professional and personal friendship that has
lasted for 37 years. We now lecture together in a continuing educa-
tion course that allows us to travel together all over the country.
Dr. Wilkins’ influence on me and almost every other hygienist in the
country has been profound. She continues to inspire me to do my
best to keep working and contributing to our profession.
CDHA Journal – Summer 2010 25
Anna Matsuishi Pattison received her
BS degree in Dental Hygiene from the
University of Southern California and
her MS degree in Dental Hygiene from
Columbia University. She has been an
Associate Professor at USC for over 30
years and has served as Chair of the
Department of Dental Hygiene. Ms.
Pattison has been a featured speaker
throughout then US, Asia, Europe, Australia and New Zealand. She
is currently the Co-Director with her husband, Dr. Gordon Pattison,
of the Pattison Institute which offers lectures and hands-on instru-
received the Pfizer-ADHA Excellence in Dental Hygiene Award and
the USC School of Dentistry Alumnus of the Year Award. In 2006
she received the California Society of Periodontists Award. In 2009
she was selected to be inducted into the USC School of Dentistry
Hall of Fame. Anna is currently editor-in-chief of Dimensions of
Dental Hygiene.
Pharmacology references continued from page 11
9. Tonetti MS, D’Aiuto F, Nibali L, et al. Treatment of periodontitis and endothelial
function. N Engl J Med. 2007;356(9): 911-20.
10. The American Academy of Periodontology (AAP). J. Periodontol. 2007;71: 125-40.
11. Tomás I, García-Caballero L , Cousido MC, Limeres J, Álvarez M, Diz P.
Evaluation of chlorhexidine substantivity on salivary flora by epifluorescence
microscopy. J Oral Dis. 2009;16(6): 428-33.
12. Palombo EA. Traditional medicinal plant extracts and natural products with
treatment of oral diseases. eCAM. 2009;1-15.
13. Food and Health Agricultural Organization of the United Nations and World
Health Organization. Guidelines for the evaluation of probiotics in foods. Joint
FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of
Probiotics in Food. 2002. Available from: ftp://ftp.fao.org/es/esn/food/
wgreport2.pdf
14. Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G. Decreased gum
Swed Dent J. 2006;30(2): 55-60.
15. GUM PerioBalance. A breakthrough in oral healthcare. 2009. Available from:
http://www.periobalance.com/default.aspx.
16. Evoraplus. Healthy gums and teeth. 2009. Available from: http://evoraplus.com/
index.php?option=com_content&view=section&layout=blog&id=10&ltemid-57
17. Sunde PT, Olsen I, Enersen M, Grinde B. Patients with severe periodontitis and
subgingival Epstein-Barr virus treated with antiviral therapy. J Clin Vir. 2008;42:
176-8.
18. Sahin S, Saygun I, Kubar A, Slots J. Periodontitis lesions are the main source of
salivary cytomegalovirus. Oral Micro Immunol. 2009;24: 340-2.
19. Liu P-F, Zhu W-H, Huang C-M. Vaccines and photodynamic therapies for oral
microbial-related disease. Curr Drug Metab. 2009;10(1): 90-4.
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