This document discusses the use of chemotherapeutic agents in periodontal therapy. It begins by providing background on the history of periodontal disease treatment and the rationale for using antimicrobial agents. It then defines key terms related to chemotherapeutic agents. The document goes on to discuss various classes of antiseptics, antibiotics, and other agents that have been used, including their mechanisms of action, formulations, and side effects. A focus is placed on agents like chlorhexidine, tetracycline, and metronidazole. Indications and advantages/disadvantages of systemic versus local drug delivery are also summarized.

2. CHEMOTHERAPEUTIC AGENTS IN
PERIODONTAL THERAPY
PRESENTED BY :
DR. VISHAKHA SRIVASTAVA
MDS PART I

3. INTRODUCTION
• By 1960’s and 70’s – Periodontitis
• From 1990’s - Regenerative procedures
• Regular mechanical removal.
• If periodontal disease- non – specific continuous plaque suppression
and specific plaque therapy.
• Thus specific elimination and reduction of pathogenic bacteria from
plaque becomes necessary.
• Thus the value of administering antimicrobial agents as a quick and
in expensive means of supporting mechanical debridement is worthy
of consideration.

4. TERMINOLOGIES
1.Chemotherapeutic agent: is a general term used for a chemical agent that
provides a clinical therapeutic benefit.
2.Antiseptics: Chemical anti microbial agent that destroys micro organisms when
applied topically or subgingivally either in intact dermal surface, mucous
membrane or wounds.
3.Anti microbial agents: Designates synthetic as well as naturally obtained drugs
that attenuate microorganisms.
4.Antibiotics: They are naturally occurring, semi synthetic or synthetic type of
anti -microbial agent that destroys or inhibits the growth of selective micro
organisms generally at low concentrations.
5.Disinfectants: Subcategory of antiseptics that are generally applied to inanimate
surfaces to destroy micro organisms.
6.Local drug delivery / site specific drug delivery: Application of currently
available drugs to the subgingival area.

5. History of chemotherapy in periodontal treatment:
Williams in 1897 and Miller in 1902 were among the first dental investigators to describe the dental
plaque and its relationship to dental diseases.
• As early as 1930’s clinical studies on chemical inhibition of plaque organisms were reported.
• Hartzell in 1932 - sodium ricinoleate, to detoxify the germs causing pyorrhea.
• King in 1951 – tetradecyclamine
• Harvey in 1961 - spiramycin as a chemotherapeutic agent in plaque control.
• Dal pro in 1972 - penicillin reduced the post operative complications.
• Goodson et al in "Local Drug Delivery “1979 first proposed the concept of controlled delivery in
the treatment of periodontitis
• Slots et al in 1979 - tetracycline reduced the post operative complications and it can be used as
an adjunct to periodontal therapy.
• Loesche et al in 1981 - metronidazole
• Appleman et al in 1982 - cephalexin decreased the incidence of polymicrobic bacteremia in
periodontal surgery.
• Van winkelhoff in 1989 described the use of combination therapy

6. CHEMOTHERAPY
Reducing the plaque through adjuctive chemotherapeutic agents
Systemic therapy

7. ANTISEPTICS IN PERIODONTAL THERAPY:
They are divided, that includes:
I. PHYSICAL AGENTS: Moist Heat- ±Boiling water & autoclaving, Pasteurization,
Dry heat- ±Flaming, Incineration, Baking in oven, Filtration, Radiation -
Ionizing ±X-rays and gamma rays, Non-ionizing ±UV and infra redlight,
Ultrasonic Vibrations
II. CHEMICAL AGENTS: Antibiotics, phenols, quarternary ammonium compounds
and sanguinarine. Bisbiguanides, bipyridines, quarternary ammonium
compounds, phenolic compounds, metal ions, halogens, enzymes,
surfactants, oxygenating agents, natural products, urea, amino alcohols,
saliflour, agents that increases the redox potentials.

8. • Available in three forms, the digluconate, acetate and hydrochloride salts.
• It was developed in 1940’s -----1954 as an antiseptic for skin wounds.
• Use in dentistry was initially for presurgical disinfection.
• Plaque inhibition was first investigated by Schroeder in 1969 and by Loe and
Schiott in 1970.
• Rinsing for 60 sec twice daily with 10 ml of a 0.2% chlorhexidine gluconate
solution in the absence of normal tooth cleaning inhibited plaque regrowth and
development of gingivitis.
1.Biguanides- Chlorhexidine: a diguanidohexane

9. • Mechanism of action is by binding strongly to the bacterial cell
membranes.
• At low concentration it is bacteriostatic (increased permeability).
• At high concentration it is bactericidal, (precipitates).
• It gets adsorbed to the pellicle coated teeth and shows persistent
bacteriostatic action upto 12 hours.
• It has broad spectrum of antimicrobial activity against gram positive, gram
negative bacteria, fungus and also against viruses like HBV, HIV.
Available as
i. 0.2% and 0.12% mouthrinses,
ii. 0.1% and 0.2% sprays,
iii. 1% in gels and tooth pastes, also as varnishes and chewing gums.

10. • Adverse effects includes brown discoloration, taste pertubation, enhanced
calculus formation, oral mucosal erosion, occasionally unilateral or bilateral
parotid enlargement.
• Clinical uses includes, as an adjunct to oral hygiene and professional prophylaxis,
post oral surgery including perio surgery, immediate pre operative rinsing,
patients with jaw fixation, removable / fixed orthodontic appliance wearers, in
denture stomatitis, recurrent oral ulceration, in mentally and physically
handicapped individuals.
• There are no data showing occurrence of systemic toxicity or resistance
development.

11. It includes :
i. benzalkonium chloride,
ii. benzethonium chloride,
iii. cetyl pyridinium chloride,
iv. domiphen bromide.
• Cetyl pyridinium chloride have moderate plaque inhibitary action. (It adsorbs
quickly, greater oral retention than chlorhexidine) but desorbs soon.
• Its mechanism of action is by membrane damage.
• It is available as 0.1% mouth rinse.
• Adverse effects includes initial burning sensation, brownish discoloraion of
tongue and teeth and recurrent aphthous ulcers.
2. Quarternary ammonium compounds

12. • Bacteriostatic disinfectant.
• Its action depends on its ability to penetrate the cell membrane in non ionized form.
• Listerine, is an essential oil / phenolic mouth wash which has moderate plaque inhibitary
action. It has thymol, menthol, eucalyptol, methyl salicylate, benzoic acid, boric acid and
20 % alcohol. No side effects like staining, taste pertubation etc., Hence advocated as an
effective alternative to chlorhexidine for home care use. Mechanism of action is by
protein denaturation and cell membrane damage. It is available as mouth rinses,
lozenges, chewing gums etc.,
• Triclosan, chlorinated bisphenol available in 0.1% concentration. It has weak
antimicrobial action. Its activity is enhanced by incorporating it into dentrifice
formulations or mouth washes with copolymers to improve the delivery of triclosan to
plaque bacteria & to increase the retention.
3. Phenols

13. • Heavy metals like zinc, tin and copper has antimicrobial action.
• Among these zinc salts are more potent and improves bactericidal action and
limits plaque formation.
• These salts is retained in plaque and inhibits its regrowth without affecting the
oral ecology.
• Tin is available as stannous fluoride.
• Copper salts are not used owing to the adverse effects like staining, potential
toxicity and unpleasant taste.
4. Metal ions

14. Halogens
• Iodine is available as Povidone-Iodine. Povidone is a surfactant that increases the
wetability and availability of iodine to the plaque bacteria. Iodine causes oxidation of
amino and thiol groups and interacts with unsaturated fatty acid. It has wide
antimicrobial action and is less toxic. 10% povidone iodine solution has 1% free iodine
that is used as a subgingival irrigant to decrease the risk of bacteremia especially in
medically compromised patients.
Fluorides including organic fluoride like amino fluoride and inorganic fluorides like
stannous fluoride both in 0.25% concentration has good antimicrobial action. But
organic fluorides has greater effect than inorganic type.
Chloride is available as sodium hypochlorite which is a very good disinfectant in
2.25% concentration. Concentrated solution – antiformin was used by Hecker in
1913 for treatment of periodontal diseases. It has wide spectrum of activity, non
toxic and produces no staining. Active species in this is hypochlorous acid. 0.5%
concentration is called as Dakin’s solution which is used during surgical procedures
in patients with localized juvenile periodontitis.

15. 6. Enzymes
There are two types that includes,
1. Those that interferes with bacterial attachment like dextranases and proteolytic enzymes.
Disadvantages - are slow acting, resistantance
2. Other type is that which potentiates the host defence mechanism. Enzymes like glucose
oxidase, amylo glucooxidase produce hydrogen peroxide.
This acts as a bacterial inhibitor by interfering with cell metabolism (Zendium). Disadvantage
is that it is rapidly eliminated from the oral cavity.
7. Surfactants
Detergents like sodium lauryl sulfate, sodium dodecyl sulfate causes -autolysis. It also weakens
the adhesion of substances to the surface. It is mostly incorporated in tooth paste.

16. 8. Oxygenating agents
Hydrogen peroxide, sodium perborate monohydrate. - antibacterial action of nascent oxygen especially
on anaerobes-- flushing action.
9. Natural products
Sanguinarine is an alkaloid plant extract. Its acts by blocking the receptors on bacterial surface. It has
flurescent property and is displaced under UV light..
It is available in dentrifices (veadent) and mouth washes. Subgingival delivery system (Atrigel).
Disadvantage - increased likelihood of causing oral precancerous lesions (almost tenfold)
Propolis (bee product).. Used in homeopathic remedies as an antiseptic, anti inflammatory, antimycotic
and bacteriostatic agent. Not much effective in mouthrinses or toothpastes.
10. Urea
Ineffective against plaque bacteria but has moderate action in decreasing the calculus formation.

17. 11. Amine alcohols
Delmopinol hydrochloride of 0.1% and 0.2% concentration - reduces the bacterial adherance. Also
used as pre-brush mouth rinse. Adverse effect includes that it produces transient anaesthetic
effect.
12. Salifluor
Chemically it is a salicylanide. It has antibacterial and anti inflammatory action. In 0.12%
concentration it is effective antiplaque and antigingivitis agent.
13. Agents increasing the redox potential
Methylene blue to increase the redox potential of the environment. It was found that 0.1%
methylene blue in biodegradable collagen alginate matrix degrades Porphyromonas gingivalis.

18. ANTIBIOTICS IN PERIODONTICS
The microbial etiology of inflammatory periodontal diseases
provides the rationale for use of antibiotics in periodontal
therapy.
The conditions to be fulfilled before the use of antibiotics are:
• The drug must show in vitro activity against the organisms
• A dose sufficient to kill the target organisms can be reached within
the subgingival environment.
• major local / systemic adverse effects.
• It should be safe to maintain the required concentration over a long
enough period to significantly affect the microbiota.
• Should not affect the commensal micro organisms.
• Must have practical advantage over conventional treatment
alternative like good clinical outcome, less adverse effects, cheaper,
faster etc.

19. Classification of antibiotics used in dentistry
According to the structure:
1. lactums: Have  lactum ring in their structure. Includes penicillin,
cephalosporin.
2. Aminoglycosides: Includes streptomycin, gentamycin etc.,
3. Sulphonamides: Includes sulpha drugs.
4. Tetracyclines: Those with four cycline rings. Derived from
streptomyces species.
5. Azoles: Includes metronidazoles, ornidazole etc.,
6. Fluro quinolones: Structures related to nalidixic acid e.g.,
ciprofloxacin
7. Macrolides: Includes erythromycin,azithromycin etc.,
8. Others: Includes clindamycin, vancomycin etc.,

20. According to mechanism of action:
1. Those that affects cell wall synthesis: penicillin, cephalosporins
2. That affects protein synthesis: tetracyclines, aminoglycosides, macrolides,
clindamycin
3. That affects intermediary metabolisms: sulphonamides that which affects
folic acid metabolism.
4. Affects DNA function: metronidazole
5. Affects DNA gyrase action: quinolones
According to the mode of action:
1. Bactericidal: Drugs that kill the sensitive bacteria e.g., penicillin,
metronidazole
2. Bacteriostatic: Drugs that inhibit multiplication of sensitive bacteria e.g.,
tetracyclines, erythromycin

22. The main disadvantages in use of antibiotics are super
infection, hypersensitivity and bacterial resistance.
1. Super infection: Due to destruction of commensal organisms.
2. Hypersensitivity: Antibiotics acts as haptens
i. Type I reactions like urticaria, anaphylaxis;
ii. Type II reactions like thrombocytopenia, agranulocytosis;
iii. Type III reactions like arthritis myocarditis, type IV reactions like
contact dermatitis.
3. Bacterial resistance:
i. Intrinsic: Organisms- naturally resistant
ii. Extrinsic: Organisms having genes that code for resistance are
transferred through plasmids (conjugation), phages (transduction)
etc.,

23. Bacterial resistance develops because of following reasons:
• Doses of same antibiotic are repeated within relatively
short time periods.
• Inappropriate antibiotics are prescribed.
• Sub optimal doses are given.
• Prescribed regimen is not adhered by the patients.
• The purpose of antibiotic therapy may be ,
a. Therapeutic – to treat established clinical infection
b. Prophylactic – to prevent, in high risk patients
c. Pre-emptive – to individuals prior to onset of clinical disease on
the basis of clinical / epidemiological / lab indication of disease
risk.

24. • Patients who do not respond to conventional mechanical
therapy. E.g., refractory periodontitis, aggresive
periodontitis etc.,
• Acute periodontal infection e.g., ANUG, ANUP, abscess.
• Prophylactically in medically and immuno compromised
individuals.
• As an adjunct to surgical / non surgical periodontal
therapy.
Indications:

25. Microbiological analysis:
Empirical use of antibiotics will result in bacterial resistance. Hence it is necessary
to do microbial analysis before prescribing the drugs.
Cultures; non-culture techniques like dark field or phase contrast microscope, DNA
probes. ELISA, PCR etc., are used.
Culturing technique is the only method that allows to do antibiotic
sensitivity tests.
• gram positive organisms – augmentin
• gram negative organisms – clindamycin
• extra dental gram negative organisms – ciprofloxacin
• anaerobes – metronidazole
• Porphyromonas gingivalis, Prevotella intermedia – tetracycline
• Aggregatibacter actinomycetem comitans – metronidazole  amoxycillin/
metronidazole ciprofloxacin / tetracycline.
• Porphyromonas gingivalis - azithromycin

27. Advantages:
• Reaches inaccessible areas like deep pockets, furcation
etc.,
• Also affects organisms colonizing oral mucosa and extra
dental sites like tongue, tonsil etc.,
• Eliminates pathogens from entire mouth, hence decreases
the risk of future reinfection.
• Low financial cost.
Disadvantages :
• Inability to achieve high concentration.
• Adverse drug reaction.
• Emergence of antibiotic resistance.
• Uncertain compliance.

28. TETRACYCLINE
• Introduced in 1948 as a broad spectrum bacteriostatic antibiotic. It
was first derived from Streptomyces species.
• Most widely used antibiotic, especially against juvenile and refractory
periodontitis.
• Unique property of this antibiotic is that it concentrates in periodontal
tissues about 2 to 10 times than that of serum. This helps to attach to
the root surfaces.
• Mechanism of action is that it impedes bacterial protein synthesis.
• Dosage and preparations includes, that tetracycline is given as 250 mg
four times a day for two weeks.
• Absorption is inhibited by the presence of food, milk, antacids and
iron preparations in the stomach.
• Minocycline is given as a loading dose of 200mg followed by
maintenance dose of 100 mg twice daily.
• Doxycycline as initial loading dose of 200 mg followed by maintenance
dose of 100 mg once daily.

29. • Frequent adverse effects includes, gastro intestinal intolerance,
candidiasis, interaction with oral contraceptives, if given in pregnant
mother or children it gets attaches to bones and teeth causing
discoloration of teeth.
• Minocycline causes ataxia, vertigo. Infrequent effects includes
phototoxicity, hepatotoxicity, nephrotoxicity, intracranial tension.
• Demeclocycline causes nephrogenic diabetes insipidus. Outdated
tetracycline causes ‘fanconi syndrome’ affecting the renal tubules.
• Resistance develops to tetracycline by either tetracycline efflux,
ribosomal protection or by production of tetracycline inactivating
enzymes.

30. Non-antibiotic properties of tetracyclines:
• Antiinflammatory
• Immunosuppresant
• Inhibitor of lipase and collagenase.
• Enhances the gingival fibroblast cell attachment.
• Enhances bone regeneration.
• Prevents epithelial migration.
• Sclerosing agent.
Anticollagenase action:
• Low dose tetracycline (doxycycline 20 mg twice daily - PERIOSTAT) and
Chemically Modified Tetracycline (CMT) like 4- dedimethylamino
tetracycline has anticollagenase action especially against MMP 8, MMP
9 and MMP 13. Mechanism of action is that it acts on secondary zinc
and calcium ions outside the catalytic domain of collagenase thus
altering the conformity of the enzyme molecule.

31. METRONIDAZOLE
• The synthetic nitroimidazole group was developed in 1959 to treat
protozoal infections.
• In 1962, Schinn observed that ANUG disappeared in patients while treating
Trichomonas vaginalis in them. In early 1970’s Davies et al confirmed that it
was bactericidal to obligate anaerobes especially against black pigmented
Bacteroids.
• Mechanism of action is that the inactive drug is reduced in anaerobic
environment by nitroreductase to nitro, nitroso free radicals that are toxic
to DNA, breaking them into strands causing cell death. Resistance rarely
develops. Most commonly prescribed regimen is 250 mg thrice/four times
daily for 7 to 10 days.

32. • Frequent adverse effects are that it causes gastro intestinal discomfort, metallic taste. In
patients taking alcohol causes disulfiram like effect. Interferes with the metabolism of warfarin
and lithium compounds.
• Infrequent effects include at high doses causes peripheral neuropathy, leukopenia, furred
tongue. It is considered it is a teratogen and a mutagen. Hence it should be avoided in
pregnant mothers.
• Empirically it is used in case of abscess and ANUG. It also is effective in treating severe
periodontitis. To treat refractory and juvenile periodontitis it is given in combination therapy
with amoxycillin or ciprofloxacin.

33. PENICILLIN
• These are most widely used antibiotic.
• They are natural and semisynthetic derivative of broth cultures of
penicillium mold.
• They inhibit cell wall synthesis and are bactericidal.
• Penicillin G is the natural penicillin, acid resistant penicillin is
penicillin V,
•  lactamase resistant ones are methicillin and cloxacillin,
• Extended spectrum penicillin that act against both gram positive
and negative organisms include amoxycillin, ampicillin,
carbencillin etc.,
• These are effective against most periodontal pathogens except
Actinobacillus actinomycetum comitans.

34. • Usual dosage of amoxycillin is 250 / 500 mg thrice daily for 8 days.
Resistance develops in  lactamase producing organisms. One approach to
overcome this vulnerability is to add it with lactamase inhibitor like
clavulanic acid i.e., Augmentin which is a combination of 250 / 500 mg
amoxycillin with 125 mg of potassium clavulanate. This combination is
successfully used in refractory periodontitis with gram positive subgingival
flora.
• Frequent adverse effects includes diarrhea, resistance, hypersensitivity
reactions (10 % of population is hypersensitive). Infrequent effects includes
hematological toxicity, encephalopathy, pseudomembranous colitis
(ampicillin).

35. FLUROQUINOLONES
• These are derivatives of Nalidixic acid and includes ciprofloxacin which is
active against gram negative rods including all facultative and some anaerobic
periodontal pathogens.
• At present ciprofloxacin is the only antibiotic to which all the strains of
actinobacillus are susceptible.
• Mechanism of action of this drug is that it interferes with the action of DNA
gyrase and causes cell death. Because of this mode of action resistance
transference is very less.

36. • Used in the dosage of 500 mg twice daily for ten days.
Oflaxacin is a newer form of this group which is of lesser
dosage and of with less side effect.
• A subgingival delivery device of oflaxacin is also
available as PT-01. Frequent adverse effects of this
group includes nausea, vomiting, bad taste, head ache,
insomnia, pruritis. Infrequent effects includes
photosensitivity, rupture of achilles tendon,
hepatotoxicity, pseudomembranous colitis.

37. MACROLIDES
• Lactone ring with deoxy sugars attached.
• It inhibits protein synthesis by attaching to 50 S ribosomes.
• Erythromycin do not concentrate in GCF and hence not used.
• Spiramycin is active against gram positive organisms and is excreted in high concentration in
saliva. Used as an oral penicillin substitute. It is present in GCF for prolonged periods of
time even when the serum levels falls down. It is a safe and non toxic drug with less side
effects.
• Azithromycin (Zythromax) is active against gram negative anaerobes and concentrate more
in diseased periodontium more than healthy one. After initial loading dose of 500 mg, 250
mg / day for five days is given as a regimen. It penetrates well into the fibroblasts and
phagocytes and is concentrated about 100 to 200 times greater than the extracellular
compartment. It is actively transported to the sites of inflammation by phagocytes.

38. CLINDAMYCIN
• Discovered in 1962 as lincomycin from the soil samples of Lincoln.
• It is used mainly in penicillin resistant cases. Its mode of action is by
inhibiting protein synthesis. Penetrates well into the GCF and is very effective
against most periodontal pathogens with exceptions of Actinobacillus
actinomycetum comitans and E.corrodens..
• It is bacteriostatic at low concentration and bactericidal at high
concentration.
• Dosage of 150 mg qid for ten days or 300 mg bid for eight days.
• Frequent side effects includes nausea, diarrhea, rashes. Infrequent side
effects includes pseudomembranous colitis, hepatitis. Pseudomembranous
colitis is a serious side effect and it can be treated by vancomycin 500mg qid
or metronidazole 200 mg qid.

39. COMBINATION THERAPY
Periodontal infection is a mixed infection --one antibiotic should be given either serially or in
combination. This should be given after culture and sensitivity tests.
The advantages of combination therapy includes:
synergistic action of combined drugs.
Less adverse effects.
Prevents emergence of resistant strains.
Antibiotics that are static needs rapidly dividing organisms and hence these
should not be given with cidal drugs. Hence bacteriostatic and cidal drugs should be given only
serially and not in combination.
The most commonly used combination in periodontal infection includes:
o Metronidazole 200 mg  Amoxycillin 250 mg tid for 7 days
o Metronidazole 200 mg  Augmentin tid for 7 days
o Metronidazole 400 mg  Ciprofloxacin 500 mg bid for 8 days.
o The combination of metronidazole and amoxycillin makes A..a to be
o susceptible because of the synergistic action of the hydroxy metabolite part of metronidazole

40. State of Art Review, J Periodontol, 2002

41. HOST MODULATION
Doxycycline Hyclate
• The FDA recently approved for doxycycline
hyclate (Periostat) as an adjunct.
• Periostat, available as a 20-mg capsule of
doxycycline hyclate, is prescribed for use by
patients twice daily.
• The mechanism of action is by suppression of
the activity of collagenase, particularly that
produced by polymorphonuclear leukocytes.
• Although this drug is in the antibiotic family,
it does not produce antibacterial effects
because the dose of 20 mg twice daily is too
low to affect bacteria. As a result, resistance
to this medication has not been seen.

42. • Following activation of inflammatory cells in the periodontium
by bacteria, phospholipids in the plasma membranes of cells are
acted on by phospholipase. This leads to the liberation of free
arachidonic acid, which then can be metabolized into
prostaglandins, thromboxanes, and prostacycline by the enzyme
cyclooxygenase. The lipoxygenase pathway can produce
leukotrienes and hydroxyeicosatetraenoic acids from
arachidonic acid.
• Cyclooxygenase pathway products (e.g., prostaglandins) may be
important mediators of some pathologic events occurring in
periodontal diseases. Therefore modulation of the host's
inflammatory response to bacteria may alter the incidence and
severity of periodontal disease.
• Nonsteroidal antiinflammatory drugs (NSAIDs) 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.
Nonsteroidal Anti inflammatory Drugs

44. • Some NSAIDs have been shown to affect the response
of polymorphonuclear neutrophils (PMNs) to
inflammation not related to prostaglandin inhibition.
• Beneficial effects of NSAIDs have also been found
after topical application .
• Drugs such as flurbiprofen, ibuprofen, mefenamic
acid, and naproxen have been studied.
• Flurbiprofen appears to inhibits PMN migration,
reduces vascular permeability, and inhibits platelet
aggregation by inhibiting cyclooxygenase.

46. • The earliest form of local drug delivery was subgingival
irrigation. But the major disadvantage was short duration
of action in these system.
• The concept of controlled release delivery of therapeutic
agents was championed and developed into viable
concept primarily by Dr. Max. Goodson in 1979.
• His first delivery device involved hollow fibers of
cellulose acetate filled with tetracycline. 95% of the drug
was released within two hours and the therapeutic level
was maintained for 24 hrs.

47. Advantages:
1.Avoidance of development of antibiotic resistance among the gut
microflora.
2. Elimination of systemic side effects.
3. Greater concentration of drug in diseased sites.
4. Less overall dosage of drugs.
5. Improved patient compliance.
Disadvantages:
1. More expensive.
2. Does not penetrate deeply into the tissues.
3. Little effect on potential reservoirs of reinfection ( tongue,
tonsil)

48. 1. Goodson in 1985 suggested three important criteria for succes
2. Must sustain the concentration of drug in the pocket for sufficient
lengsful local drug delivery that includes:
3. Device must deliver drug to the base of the pocket.
4. Must deliver drug at microbiologically efficacious concentration. th of time and in
sufficient concentration to be clinically effective.
Greenstein and Polson in 1998 added up certain other criteria like:
1. Ease of placement.
2. Retention after placement.
3. Biodegradable.
4. No emergence of bacterial resistance.
5. Safe with minimal side effects.
6. Should be effective only against periodontal pathogens and not on commensal
microflora.

49. Controlled release drugs may with or without rate controlling device.
a. Without rate controlling device: Hollow fibers filled with agents that
are released simply by diffusion through reservoir walls. They release
drug so rapidly and so qualify only marginally.
b. With rate controlling device: They may be of three types, that
includes,
• The drug is coated with lipids like bees wax / ethyl cellulose. It is
carried in a non aqueous carrier. The number of coats each granule has
dictates its dissolution rates.
• ii. Drug is granulated in inert plastic matrix polymer membranes or
monolithic matrices like polyethylene, PMA, PVA. It is slowly released
by leaching through body fluids. Initial release is from surface of the
polymer. Deeply embedded drug is released depending on the
concentration gradient. These are not biodegradable.
• iii. These are biodegradable polymeric matrices containing the drugs.
The degradation is enzymatic. These are less dependant on the
concentration gradient.

50. Tetracycline containing fibers (ACTISITE)
• First local drug delivery system available in U.S.
• It is an Ethylene Vinyl Acetate copolymer fiber of 0.5 mm diameter containing tetracycline
12.7 mg / 9 inches. When packed in pocket, needed to be applied in successive layers to
completely fill the pocket. It is non resorbable cylindrical monolithic fibers with 25%
tetracycline hydrochloride.
Advantages:
• Potent and nontoxic .
Disadvantages:
• it needs considerable learning curve to gain proficiency at placement.
• Length of time needed to place the fiber is also more i.e 10 min / tooth.
• needs second appointment for removal.
• If placed in more than 12 teeth it causes candidiasis.
1. Tetracycline containing fibers (ACTISITE)

51. • It is a gel system consists of 10% doxycycline in
syringeable gel.
• Syringe A, contains the delivery vehicle which is bioresorbable
flowable polymeric formulation composed of poly (DL – Lactide)
dissolved in N-Methyl-2 pyrrolidone.
• Syringe B contains 50 mg of doxycycline. It is injected as gel and
solidifies within the pocket after interacting with GCF and saliva.
2. Subgingival delivery of doxycycline ( ATRIDOX):

52. 3. Subgingival delivery of minocycline ( Arestin, Dentomycin,
Periocline):
Three modes of local application are available:
a. Films: Films of ethylcellulose containing 30 % of minocycline cast from
ethanol/ chloroform is used. Addition of polyethylene glycol may be
added to increase the release of the drug to the plaque micro
organisms.
b. Micro spheres: Micro encapsulated in resorbable poly lactide slow
releasing polymers. Used in plastic syringe. 4 mg of micro spheres
contain about 1 mg of minocycline.
c. Oinment: 2% minocycline hydrochloride is used in the form of oinment.
0.5 g of oinment contains about 10 mg of minocycline that is supplied in
a disposable polypropylene applicator.

53. • Oil based 25 % metronidazole gel in glyceryl mono-oleate
and sesame oil is applied in viscous consistency in pocket.
It is liquidized by body temperature and hardens again
forming crystals in contact with water. It is also employed
in conjugation with GTR.
• Both minocycline and metronidazole follows first order
kinetics. The amount of drug release depends on the total
concentration of the drug. Hence maximum release is
during the first 24 hrs and these are sustained drug
delivery devices.
4. Metronidazole gel (Elyzol):

54. 5. Subgingival delivery of Chlorhexidine ( PERIOCHIP):
• It is resorbable delivery system measuring about 4  5  0.35 mm.
• It contains biodegradable hydrolyzed gelatin matrix cross linked with
glutaraldehyde and also contains glycerin and water into which 2.5 mg of
chlorhexidine gluconate has been incorporated. 100 g / ml is present for
atleast 7 days in GCF. Rounded at one end and inserts easily in less than a
minute into pockets of greater than 5 mm.
• Advantages includes that it is resorbable, no adverse effects like staining, no
emergence of bacterial resistance or hypersensitivity reactions.
• Disadvantages is that its action is reduced in the presence of organic matter.

55. REFERENCES:
• Carranza 9th, 10th edition
• Chemotherapeutics: antibiotics and other antimicrobials,
Periodontology 2000, vol. 36, 2004, 146–165
• Periodontal medicine:The emergence of a new branch of
periodontology, Periodontology 2000, vol. 23, 2000, 9–12
• Chemotherapeutic Agents and Periodontal Therapy Their Impact on
Clinical Practice Sebastian C. Ciando
• Antimicrobial strategies for Treatment of periodontal Diseases,
Periodontology 2000, vol. 5, 1994, 142-168
• Text book of pharmacology, Harshmohan, K.D. Tripathi
• Jan Lindhe