Drugs in periodontics

DRUGS USED IN PERIODONTAL THERAPY

DRUGS USED IN PERIODONTAL THERAPY
CLASSIFICATION
• On the basis of the use of drugs
• On the basis of administration

To treat infections
Antibiotics
To control pain &
inflammation
NSAIDs
Anesthetics
Antipyretic
Others
Antiseptics
Disinfectants
Drugs with specific
application
Hormones and
related drugs
ON THE BASIS OF THE USE OF DRUGS
(PART – I)
(PART – II)
(PART – III)

ON THE BASIS OF ADMINISTRATION
Systemic drug delivery Local drug delivery
(PART – IV)

C
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• Introduction
• Guidelines for use of antibiotics in periodontal therapy
• Classification of antibiotics
• Mechanism of action
• Indications for antibiotic use in periodontal therapy
• Antibiotic dosing principles
• Local vs systemic administration
• Antibiotic therapy in periodontal diseases
• Serial systemic therapy
• Combination therapy
• Disadvantages of combination therapy
• Resistance to antibiotics
• Failure in antibiotic therapy
• Conclusion
PART – I (ANTIBIOTICS)

INTRODUCTION
• Periodontal diseases – disturbed pathological state of the
periodontium.
• These diseases are usually caused by bacterial infections.
• Bacterial growth ultimately leads to the formation of periodontal
pockets and affects bone causing periodontal diseases.
Newman and Carranza’s Clinical Periodontology, 13th edition.

How to treat periodontal diseases ?
• By mechanical removal of local factors –
plaque
calculus
• Mechanical removal includes :
1. Manual instrumentation
2. Machine drive instrumentation
• By the use of anti-infective agents as an adjunct to
mechanical periodontal therapy.
Newman and Carranza’s Clinical Periodontology, 13th edition

• Anti-infective agents –
An anti-infective agent is a chemotherapeutic agent that acts by
reducing the number of bacteria present.
It is a general term that encompasses antibacterial, antifungals,
antibiotics, antivirals, and anti-protozoans.
• Antibiotics -
An antibiotic is a naturally occurring, semisynthetic, or synthetic
type of anti-infective agent that destroys or inhibits the growth of
select microorganisms, generally at low concentrations.
Antibiotics do not remove calculus and bacterial residues, and this
is traditionally perceived to be an essential part periodontal therapy.

GUIDELINES FOR USE OF ANTIBIOTICS
IN PERIODONTAL THERAPY
• The clinical diagnosis and situation dictate the need for possible
antibiotic therapy as an adjunct in controlling active periodontal
disease as the patient’s diagnosis can change overtime.
• Continuing disease activity is an indication for periodontal
intervention and possible microbial analysis through plaque
sampling.

• When used to treat periodontal disease, antibiotics are selected
based on patient’s medical and dental status, current
medications, and results of microbial analysis, if performed.
• Microbial samples may be obtained from individual pockets
with recent disease activity or from pooled subgingival sites . A
pooled subgingival sample may provide a good representation
of the range of periodontal pathogens to be targeted for
antibiotic therapy.

• Antibiotics have also been shown to have value in reducing the
need for periodontal surgery in patients with chronic
periodontitis.
• Systemic antibiotic therapy should be an adjunct to a
comprehensive periodontal treatment plan. An antibiotic
strength 500 times greater than the systemic therapeutic dose
may be required to be effective against the bacteria arranged in
biofilms.

• Slots et al described a series of steps using anti-infective
agents for enhancing regenerative healing. They recommend
starting antibiotics:
12 days before surgery and continuing for at least
8 days, however, the value of this regimen has not been well
documented.
• Haffajee et al concluded that data support similar effects for
most antibiotics. Risks and benefits concerning antibiotics as
adjunct to periodontal therapy must be discussed with the
patients before the antibiotics are used.

CLASSIFICATION
• On the basis of chemical structure:
1. Sulphonamides
2. Quinolones – norfloxacin , ciprofloxacin
3. Tetracycline – oxytetracycline, doxycycline
4. Aminoglycosides – streptomycin, gentamycin, neomycin
5. Macrolides
6. Glycopeptides antibiotics : vancomycin
7. Nitroimidazole : metronidazole, tinidazole
8. β - lactam antibiotics : penicillin
K.D. Tripathi. Essentials of pharmacology

• On basis of mechanism of action :
 Inhibit cell wall synthesis –
- Penicillin, cephalosporins, vancomycin
 Inhibit protein synthesis –
- tetracycline, chloramphenicol, erythromycin
 Misreading of m-RNA code and affect permeability –
- Aminoglycosides, streptomycin

Cause leakage from cell membrane –
- polymyxins, bacitracins, nystatin
 Interfere with DNA function –
- Metronidazole, rifampicin
 Interfere with intermediary metabolism –
- sulfonamides, trimethoprim

• Type of organisms against which primarily active
Antibacterial – penicillin, erythromycin, aminoglycosidess
Antifungal – amphotericin B, ketoconazole
Antiviral – acyclovir, zidovudine, amantadine
Antiprotozoal – chloroquine, metronidazole

• On the basis of type of action –
Bacteriostatic – agents that reversibly inhibit growth of bacteria –
sulfonamides, tetracyclines, erythromycin
Bactericidal – those with an irreversible lethal action on bacteria –
penicillin, aminoglycosides, cephalosporins
• On the basis of spectrum of activity –
Narrow spectrum – penicillin G, erythromycin
Broad spectrum – tetracyclines, chloramphenicol

INDICATIONS FOR ANTIBIOTIC USE IN
PERIODONTAL THERAPY
• As an adjunct to surgical or non-surgical periodontal therapy.
• As prophylaxis in medically compromised patient.
• Patients who do not respond to conventional periodontal therapy.
• Patients with acute periodontal infections with systemic
manifestations.
AJ Van Winkelhoff, TE Rams, J Slots, Systemic Antibiotics in Periodontics. J Periodontol 2004;75:1553-1565

ANTIBIOTIC DOSING PRINCIPLES
• Employ high doses for a shorter duration : high concentrations are
more critical with aminoglycosides, metronidazole and
quinolones.
• Use an oral antibiotic loading dose.
• Achieve blood levels of the antibiotic at 2-8 times the minimal
inhibitory concentration.
• Use frequent dosing intervals : so as to maintain relatively
constant blood levels.
• Determine the duration of therapy by remission of disease.
TJ Pallasch Pharmacokinetic Principles of Antimicrobial Therapy. Periodontol 2000. 1996 Feb;10:5-11

LOCAL VS SYSTEMIC ADMINISTRATION
• Local release of antimicrobial agents or antibiotics is normally
carried out using fibers, gels, chips or microspheres.
• The greatest advantage of this usage is avoidance of the side
effects of drugs prescribed systemically and a diminished chance of
developing bacterial resistance to the medications.
• local antimicrobial therapy has more commonly been used during
the maintenance phase, for treating remaining and isolated active
pockets.
Feres M et al, Systemic antibiotics in the treatment of periodontitis. Periodontology 2000, Vol. 67, 2015, 131–186

• The disadvantages of systemic antibiotics over locally applied
antibiotics include adverse drug reactions, uncertain patient
compliance and lower concentration of the drug at subgingival
sites.
• The severest criticism of the indiscriminate use of systemic
antibiotics is the development of bacterial resistance.
Feres M et al, Systemic antibiotics in the treatment of periodontitis. Periodontology 2000, Vol. 67, 2015, 131–186

ANTIBIOTIC THERAPY IN PERIODONTAL DISEASES
TETRACYCLINE
• Have the ability to concentrate in the periodontal tissues and
inhibit the growth of Aggregatibacter actinomycetemcomitans
• Tetracycline are a group of antibiotics that are produced naturally
from certain species of Streptomyces or derived semi-
synthetically.
• These are bacteriostatic and are effective against rapidly
multiplying bacteria.
• They generally are more effective against gram-positive bacteria
than against gram-negative bacteria
RA Seymor et al, Tetracyclines in the treatment of periodontal diseases. J Clin Periodontol 1995: 22: 22-35.

• Tetracycline exert an anticollagenase effect that can inhibit tissue
destruction.
• Their concentration in the gingival crevice is 2 to 10 times that
found in serum
• Mode of action –
-Act by inhibition of protein synthesis by binding to 30s ribosome in
the susceptible organism.
-In high concentrations they may cause alterations in the
cytoplasmic membrane, which results in leakage of nucleotides or
other compounds of the cell.
-This accounts for rapid inhibition of DNA replication, which occurs
at site of membrane.
RA Seymor et al, Tetracyclines in the treatment of periodontal diseases. J Clin Periodontol 1995: 22: 22-35.

• Clinical use –
-Tetracycline have been investigated as adjuncts for the treatment of
LAP, and other types of aggressive periodontitis.
-Systemic tetracycline can eliminate tissue bacteria and has been
shown to arrest bone loss and suppress A. actinomycetemcomitans
levels in conjunction with scaling and root planing.
• Dosage regimen –
- Treatment with tetracycline requires the administration of 250 mg
four times daily
• Side effects –
- Include gastrointestinal disturbances, photosensitivity,
hypersensitivity, blood dyscrasias, dizziness, and headache. Tooth
discoloration occurs when this drug is administered to children who
are 12 years old or younger

MINOCYCLINE
- Minocycline is effective against a broad spectrum of
microorganisms.
- In patients with adult periodontitis, it suppresses spirochetes and
motile rods as effectively as scaling and root planing, with
suppression evident up to 3 months after therapy.
- Minocycline can be given twice daily.

• Minocycline administered at a dose of 200 mg/day for 1 week
results in a reduction of total bacterial counts, complete
elimination of spirochetes for up to 2 months, and improvement
of all clinical parameters
• Side effects are similar to those of tetracycline; however, there is
an increased incidence of vertigo.
• It is the only tetracycline that can permanently discolour erupted
teeth and gingival tissue when administered orally.

DOXYCYCLINE
• Has the same spectrum of activity as minocycline and can be
equally effective.
• Because doxycycline can be given only once daily, patients may
be more compliant.
• Side effects are similar to those of tetracycline hydrochloride;
however, it is the most photosensitizing agent in the tetracycline
category.
• Recommended dosage when doxycycline is used as an anti-
infective agent is 100 mg twice daily the first day, which is then
reduced to 100 mg daily

• To reduce gastrointestinal upset, 50 mg can be taken
twice daily after the initial dose.
• When given as a sub-antimicrobial dose (to inhibit
collagenase), 20 mg of doxycycline twice daily is
recommended.9

METRONIDAZOLE
• It is bactericidal to anaerobic organisms.
• Metronidazole is not the drug of choice for treating A.
actinomycetemcomitans infections.
• It is also effective against anaerobes such as Porphyromonas
gingivalis and Prevotella intermedia.
- Metronidazole has been used clinically to treat acute necrotizing
ulcerative gingivitis, chronic periodontitis, and aggressive
periodontitis.
Gary Greenstein, The Role of Metronidazole in the Treatment of Periodontal Diseases. J Periodontol 1993; 64:1- 15

metronidazole enters mammalian cells as well as
aerobic and anaerobic bacteria by diffusion.
The nitro group of the compound is reduced by
nitroreductase , a concentration gradient is created and
more drug enters the cells
Reduction precipitates release of toxic products (nitro,
nitroso, nitroso-free radicals)
These intermediates interfere with DNA synthesis
causing disruption of involved organisms.
MECHANISM OF ACTION

• Dosage –
- When administered systemically (i.e., 750 mg/day to 1000 mg/day
for 2 weeks), metronidazole reduces the growth of anaerobic flora,
including spirochetes, and it decreases the clinical and
histopathologic signs of periodontitis.
- The most common regimen is 250 mg 3 times daily for 7 days.
- Metronidazole has an Antabuse effect when alcohol is ingested.
- Metronidazole also inhibits warfarin metabolism and it prolongs
prothrombin time.

PENICILLIN
• Penicillin are natural and semisynthetic derivatives of broth
cultures of the Penicillium mould.
• They inhibit bacterial cell wall production and therefore are
bactericidal.
• Major activity in the gram positive spectrum
• Only the extended spectrum penicillin, posses substantial
antimicrobial activity for gram negative species.
Goodson JM, Antimicrobial strategies for treatment of periodontal diseases. Periodontology 2000, Vol. 5, 1994, 142-1 68

- may be useful for the management of patients with aggressive
periodontitis in both localized and generalized forms.
Exhibits high antimicrobial activity at levels that occur in GCF
for all periodontal pathogens.
• Dosage -
- The recommended dosage is 500 mg 3 times daily for 8 days.

AMOXICILLIN
• It is a semisynthetic penicillin with an extended anti-infective
spectrum that includes gram-positive and gram-negative bacteria.
• Amoxicillin is susceptible to penicillinase, which is a β-
lactamase produced by certain bacteria that breaks the penicillin
ring structure and thus renders penicillin ineffective.
• The recommended dosage is 500 mg 3 times daily for 8 days.

Amoxicillin–Clavulanate Potassium
• Combination of amoxicillin with clavulanate potassium
makes this anti-infective agent resistant to penicillinase.
• Amoxicillin with clavulanate (Augmentin) may be useful for
the management of patients with LAP or refractory
periodontitis.
• Augmentin arrested alveolar bone loss in patients with
periodontal disease that was refractory to treatment with other
antibiotics, including tetracycline, metronidazole, and
clindamycin

CEPHALOSPORINS
• Family of β-lactams - similar in action and structure to the
penicillin.
• They are resistant to a number of β-lactamases.
• Same mode of action as penicillin, i.e. inhibition of bacterial
cell wall synthesis.
• However they bind to different protein than those which bind
to penicillin.

- Achieve high concentration in GCF.
- Effectively inhibit growth of gram negative obligate
anaerobes, fails to inhibit the gram negative facultative
anaerobes.
- Rashes, urticaria, fever, and gastrointestinal upset have all
been associated with cephalosporins.

CLINDAMYCIN
• Effective against anaerobic bacteria and has a strong affinity
for osseous tissues.
• Effective for situations in which the patient is allergic to
penicillin.
- Inhibition of protein synthesis by biding to 50 S ribosomes.
- efficacy in patients with periodontitis that is refractory to
tetracycline therapy

- Walker and Colleagues showed that clindamycin helped
stabilize refractory patients.
- It is not indicated for patients with a history of colitis
- Diarrhoea or cramping that develops during clindamycin
therapy may be indicative of colitis.
• Dosage –
- The dosage used was 150 mg 4 times daily for 10 days.
- Jorgensen and Slots33 recommend a regimen of 300 mg twice
daily for 8 days.

CIPROFLOXACIN
• Ciprofloxacin is a quinolone that is active against gram-
negative rods, including all facultative and some anaerobic
putative periodontal pathogens.
• A potent inhibitor of gram negative bacteria with MIC values
ranging from 0.2 to 2 µg/ml.
-Inhibition of bacterial DNA replication and transcription by
inhibiting the enzyme DNA gyrase.

- Demonstrates a minimal effect on Streptococcus species,
which are associated with periodontal health.
- Ciprofloxacin is the only antibiotic in periodontal
therapy to which all strains of A.
actinomycetemcomitans are susceptible.
- Nausea, headache, metallic taste in the mouth, and
abdominal discomfort have been associated with
ciprofloxacin.
- Also been reported to enhance the effects of warfarin and
other anticoagulants

MACROLIDES
• Contain a many-membered lactone ring to which one or more
deoxy sugars are attached.
• They inhibit protein synthesis by binding to the 50S
ribosomal subunits of sensitive microorganisms.
• Macrolides can be bacteriostatic or bactericidal, depending on
the concentration of the drug and the nature of the
microorganism.
• The macrolide antibiotics used for periodontal treatment
include erythromycin, spiramycin, and azithromycin.

Erythromycin
• Extremely safe drug that has been recommended as an
alternative to penicillin for allergic patients.
• Gingival fluids level suggest that only a small portion reaches
the periodontal pocket by oral route.
• Principal limitation is its poor tissue absorption.

• Erythromycin does not concentrate in GCF and is not
effective against most putative periodontal pathogens.
• For these reasons, erythromycin is not recommended as an
adjunct to periodontal therapy

Spiramycin
• It is active against gram-positive organisms; it is excreted in
high concentrations in saliva.
• It is used as an adjunct to periodontal treatment.
• Excreted in high concentrations in saliva.
• Spiramycin has a minimal effect on attachment levels

Herrera et al. in a meta-analysis evaluating spiramycin,
amoxicillin plus metronidazole showed a statistically significant
additional effect of spiramycin in addition to other antibiotics
with regard to probing depth reduction for sites with initial
probing depths of >6mm.

Azithromycin
• Azithromycin is a member of the azalide class of macrolides.
• It is effective against anaerobes and gram-negative bacilli.
• After an oral dosage of 500 mg 4 times daily for 3 days,
significant levels of azithromycin can be detected in most
tissues for 7 to 10 days.
• The concentration of azithromycin in tissue specimens from
periodontal lesions is significantly higher than that of normal
gingiva

• Azithromycin penetrates fibroblasts and phagocytes in
concentrations that are 100 to 200 times greater than that
of the extracellular compartment.
• Azithromycin is actively transported to sites of
inflammation by phagocytes, where it is released directly
into the sites of inflammation as the phagocytes rupture
during phagocytosis.
• Therapeutic use requires a single dose of 250 mg/day for 5
days after an initial loading dose of 500 mg

ANTI FUNGAL DRUGS
• Used for superficial or deep fungal infection.
• Associated with the introduction and use of immunosupressant
drugs, broad spectrum antibiotics, implants and emergence of
aids.
• Due to result of breakdown of host defence mechanisms by the
above agents, Saprophytic fungi easily invade living tissue.
• Candida albicans is normally resident in oral cavity.
• Two important antifungal drugs are – Amphotericin – B,
Ketoconazole.

Amphotericin B –
• Obtained from Streptomyces nodosus. Insoluble in water and
unstable in aqueous solution.
• Active against wide range of fungi – Candida Albicans,
Blastomyces Dermatotidis, Aspergillus, Cryptococcus
Neoformans etc.
• Mode of action-
Polyenes in the structure have high affinity
for ergosterol present in fungal cell membrane. They combine with
it, get inserted into the membrane and several molecules together
orient to form micropore, leading to increased permeability of the
cell wall.

• Dosage –
Can be used orally, 50-100 mg QID, for intestinal
moniliasis.
• Topically used for vaginits, otomycosis etc.
• Fungizone Intravenous, Mycol, 50mg vial diluted to 500ml
with glucose solution for systemic mycosis.
• Adverse effects –
Acute reaction – chills, fever, aches, nausea, vomiting etc lasting
for atleast 2-5 hours.
Long term toxicity – Nephrotoxicity, inability to concentrate
urine, etc.

Fluconazole –
• Fungicidal concentrations are achieved in saliva, nails etc.
• Indications include mucosal candidiasis in both normal and
immunocompromised patients.
Candida infections of the mouth, cutaneous
candidiasis, fungal keratitis.
• Dosage –
oral fluconazole 150 mg/day for 2 weeks for oral
candidiasis.

Adverse effects –
-Rash, headache, nausea, vomiting.
-Not recommended in pregnant or lactating women.

ANTI VIRAL DRUGS
• Application of anti-viral drugs in dentistry is restricted to
treatment of oropharyngeal herpes simplex and herpes labialis.
• Dentists run the risk of accidental exposure to HIV infections
and should be well informed about prophylaxis.
• Important antivirals in include –
Acyclovir
Zidovudine

ACYCLOVIR
• An anti-herpes virus drug.
• H. Simplex type I is the most sensitive followed by H.simplex
type II.
• Acyclovir turns to acyclovir triphosphate which in turn:
1. Inhibits virus DNA polymerase competitively
2. Stops lengthening of DNA strands
3. Inhibits DNA-polymerase irreversibly.

1. Mucocutaneous H. simplex –
- 5 times daily application of acyclovir 5% cream (topical)
- Oral acyclovir 200mg TDS a day.
2. Acute herpetic gingivostoamtitis –
- 200mg 5 times daily for 10 days.
3. Herpes zoster
4. Chickenpox
Oral – headache, nausea, malaise etc.
Topical – stinging and burning sensation
Intravenous – rashes, sweating and fall in BP.

ZIDOVUDINE
It is a thymidine analogue, the prototype Nucleoside reverse
transcriptase inhibitor.
- After phosphorylation in the host cell – zidovudine triphosphate
selectively inhibits viral reverse transcriptase.
- Used in HIV infected patients only in combination with at least 2
other ARV drugs.
- Anaemia and neutropenia are dose related adverse effects.
- Nausea, anorexia, abdominal pain, headache, are common at the
start of therapy but diminish later.

SERIAL SYSTEMIC THERAPY
• Antibiotics that are bacteriostatic (e.g., tetracycline) generally
require rapidly dividing microorganisms to be effective.
• They do not function well if a bactericidal antibiotic (e.g.,
amoxicillin) is given concurrently.
• When both types of drugs are required, they are best given
serially rather than in combination.
AJ Van Winkelhoff, TE Rams, J Slots, Systemic Antibiotics in Periodontics. Periodontol 2000 1996; 10:45-78.

COMBINATION THERAPY
Since the subgingival microbiota in periodontal diseases consists
of various pathogens that may differ in susceptibility – the use of
one or more antibiotics may represent a valuable approach in in
periodontal chemotherapy.

• Rams and Slots - reviewed the metronidazole– amoxicillin
and metronidazole–Augmentin combinations provided
excellent elimination of many organisms in adults with LAP
who had been treated unsuccessfully with tetracycline and
mechanical debridement.
• These drugs have an additive effect that involves the
suppression of A. actinomycetemcomitans.
• Tinoco and colleagues found metronidazole and amoxicillin to
be clinically effective for the treatment of LAP, although 50%
of patients who were treated with this regimen harbored A.
actinomycetemcomitans 1 year later

• The metronidazole–ciprofloxacin combination is effective
against A. actinomycetemcomitans; metronidazole targets
obligate anaerobes, and ciprofloxacin targets facultative
anaerobes. This is a powerful combination against mixed
infections.
• Antibiotic treatment should be reserved for specific subsets
of periodontal patients who do not respond to conventional
therapy

Disadvantages of combination therapy
• Higher cost of therapy.
• Increased chances of superinfections.
• They foster a casual rather than rational outlook in diagnosis of
infections and choice of antimicrobials.
• Increased incidence and variety of adverse effects.

RESISTANCE TO ANTIBIOTICS
MARILYN C. ROBERTS, Antibiotic toxicity, interactions and resistance development. Periodontology 2000, Vol. 28, 2002, 280–297

• Low level penicillin resistance in certain microorganism
such as pneumococci is thought to be due to mutation that
result in changes in the penicillin-binding proteins.
• Increase to resistance to several others antibiotics also
occur by mutation that result in changes in the proteins
associated with the permeability of bacterial cell
membrane.
MARILYN C. ROBERTS, Antibiotic toxicity, interactions and resistance development. Periodontology 2000, Vol. 28, 2002, 280–297

FAILURE IN ANTIBIOTIC THERAPY
FALSE FAILURE
• Erroneous diagnosis
• Underlying disease uninfluenced by antibiotic
• Inactivation of the antibiotic
PATIENT RELATED FAILURES
• Compliance failure
• Immunodepressed host
• Inappropriate administration route

PHARMACOLOGICAL FAILURE
• Insufficient amount of drug
• No attention paid to pharmacodynamic parameters
MICROORGANISM RELATED FAILURE
Wrong pathogen
Resistance acquired during therapy
Insufficient bactericidal activity

PART – II (TO RELIEVE PAIN)
C
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• Introduction
• Nonsteroidal anti-inflammatory Drugs and Antipyretics –
analgesics
• Opioid analgesics
• Anaesthetics

ANALGESIC is a drug that selectively relieves pain by acting
in the CNS or on peripheral pain mechanisms, without
significantly altering consciousness.
Opioid/narcotic/morphine like
analgesics
Non opioid/antipyretic like
analgesics or NSAIDs
• NSAIDs and antipyretic – analgesics are more commonly
employed for dental pain because tissue injury and
inflammation are the major cause of acute dental pain.
• Whereas opioid like analgesics depress CNS, produce
physical dependence, have abuse liability etc.

NON STEROIDAL ANTIINFLAMMATORY DRUGS AND
ANTIPYRETIC – ANALGESICS
CLASSIFICATION
A. Nonselective COX inhibitors –
Aspirin, ibuprofen, diclofenac, ketorolac
B. Preferential COX-2 inhibitors –
Nimesulide, meloxicam
C. Selective COX-2 inhibitors –
Celecoxib, parecoxib
D. Analgesic – antipyretics with poor anti-inflammatory action -
Paracetamol, metamizol, nefopam
Kirkwood K, Cirelli J, Rodger J and Giannobile W. Novel therapeutic approaches to treat periodontal diseases. Periodontology, 2000; 2007(43): 294–315

ASPIRIN
Acetyl salicylic acid –
Converted to salicylic acid
by the body
Hyperglycaemia at
toxic doses
Acts on peripheral
pain receptors
Uses -
Analgesic
Antipyretic
Anti-inflammatory
Dosage – 325 to 650 mg,
orally every 4 hours as
needed
Adverse effects –
Ulcers, GI irritants,
Acetyl salicylate
poisoning,
Hypersensitivity
Kirkwood K, Cirelli J, Rodger J and Giannobile W. Novel therapeutic approaches to treat periodontal diseases. Periodontology, 2000; 2007(43):
294–315

IBUPROFEN
Adverse effects – gastric
discomfort, rashes,
itching, depression,
hypersensitivity
Inhibits PG synthesis
Prolongation
bleeding time
Indications – rheumatoid
arthritis, osteoarthritis,
postoperative swelling
and inflammation
Less effective than
aspirin
Dosage –
400mg QD
Max – 2.4g

PARACETAMOL
Raises pain threshold
Weak anti-inflammatory
action
Good antipyretic
No effect on CVS
Adverse effects –
Analgesic nephropathy
Acute paracetamol
poisoning
Dosage-
0.5 – 1 m TDS
Crocin 0.5 – 1.0 g tabs
USES-
Analgesic for headache,
musculoskeletal pain,
toothache
Aspirin and paracetamol
are equieffective in
relieving pain after tooth
extraction.

Guidelines for analgesic use –
• Mild to moderate pain with little inflammation – paracetamol or
ibuprofen
• Acute but short lasting pain – ketorolac, diclofenac
• Patients with history of asthma – nimesulide, COX-2 inhibitors
• Pregnancy – paracetamol is the safest
• Hypertensive, diabetic or patient receiving long term regular
medication – possibility of drug interaction with NSAIDs should
be considered.

OPIOID ANALGESICS
• Otherwise called narcotic analgesics.
• These act on the CNS and produce depression of CNS.
• Indicated for severe pain.
• Opium – dark brown resinous material obtained from poppy
capsule.

OPIOID
ANALGESICS
FENTANYL
TRAMADOL
HEROIN
PHOLCODEINE
OXYCODONE
MORPHINE
CODEINE
SYNTHETIC
OPIATES
SEMI-SYNTHETIC
OPIATES
NATURAL
ALKALOIDS

CODEINE
Converted to morphine
by body
Methyl morphine
Dosage –
30 – 60 mg
4 times a day
Effective cough
suppressants
Used along with
NSAIDs

TRAMADOL
Synthetic centrally
acting analgesic
Adverse effects –
Sedation, drowsiness,
nausea, vomiting
Indicated for moderate
to severe pain
50 – 100 mg
4 times/day

Local anaesthetics
Inhalational
Surface
anaesthetics
Injectable Intravenous
General anaesthetics
Nitrous oxide
Halothane
Cocaine
KetamineBenzocaineProcaine
LidocaineLidocaine Propofol
Ether DiazepamBupivacaine
FentanylisofluraneTetracaineXylocaine
ANAESTHETICS

LIDOCAINE
• Introduced in 1948, good for surface as well as injection.
• Blocks conduction within 3 minutes.
• Method of action –
- Block nerve conduction by decreasing entry of Na+ ions during
upstroke of action potential.
- Block sensory nerve endings, nerve trunks, neuromuscular
junction, those structures which function through increased Na+
permeability.

- CNS effects are light headedness, dizziness, visual disturbances,
involuntary movements, convulsions and respiratory arrest.
- Cardiovascular toxicity as bradycardia, hypotension, cardiac
arrhythmia and vascular collapse.
- Hypersensitivity reactions like rashes, angioedema, dermatitis,
asthma and anaphylaxis occur.
• Dosage –
- 4% topical solution
- 2% jelly
- 2% injection (with or without adrenaline)

NITROUS OXIDE
• Colourless, odourless, heavier than air, non inflammable gas
supplied under pressure.
• Onset is quick and smooth, recovery is rapid.
• Provides conscious sedation.
• Generally used as a carrier and adjuvant to other anaesthetics.

• Advantages of N2O are rapid onset of action and rapid
recovery.
• There are few contraindications (e.g., chronic obstructive
pulmonary disease, severe emotional disturbance, early
pregnancy).
• Obstacles to the use of N2O include:
-The initial cost of equipment, the need for effective
scavenging equipment, periodic maintenance, and the concern
that long-term exposure to trace amounts of N2O can be
hazardous to dental personnel

PROPOFOL
• Oily liquid employed as a 1% emulsion for i.v. induction and
short duration anaesthesia.
• Unconsciousness occurs after 15-45 sec and lasts for 10-15
min.
• Lacks airway irritancy and particularly suited for outpatient
surgery because residual impairment is less marked.
• Incidence of post-operative nausea and vomiting is low.

PART – III ( OTHERS )
• Antiseptics and disinfectants
• Drugs with specific actions
• Hormone related drugs
C
O
N
T
E
N
T
S

DISINFECTANTS AND ANTISEPTICS
• The terms connote an agent which inhibit or kill microbes on
contact.
• Conventionally, agents used on living surfaces are called
antiseptics while those used for inanimate objects are called
disinfectants.
• Spectrum of activity is wide, reflecting non selectivity of
actions.
• However some are rather selective and are more active on
gram-positive than gram-negative bacteria.

MECHANISM OF ACTION
Oxidation of
bacterial
protoplasm
Denaturation of
bacterial
proteins
including
enzymes
Detergent like
action increasing
permeability of
bacterial
membrane.

PHENOLS
TRICLOSAN
OXIDIZING AGENTS
HYDROGEN PEROXIDE
BIGUANIDES
CHLORHEXIDINE
Broad spectrum
activity against most
oral bacteria.
Denaturation of
membrane bound
enzymes is responsible
for bactericidal
action.
Non-irritating, does not
stain teeth.
Listerine- most widely
used for bad breath,
plaque and periodontal
diseases.
Liberates nascent
oxygen which oxidizes
necrotic matter and
bacteria.
Transient antiseptic
action.
Mouthwash prescribed
in acute necrotizing
gingivitis because of
anaerobic bacteria.
Frequent use can
produce oral ulcers.
20-30% can be used as
bleaching agent on
teeth.
Powerful, non
irritating, cationic
antiseptic that disrupts
cell membrane of
bacteria.
More active against
gram positive bacteria.
Chlorhexidine oral
rinse (0.12-0.2%) or
Toothpaste (0.5-1%)
Disadvantage is
brownish
discolouration of teeth
and tongue.

DRUGS WITH SPECIFIC ACTIONS
ANTI-PLAQUE &
ANTI-GINGIVITIS
AGENTS
ANTI-CARIES
AGENTS
DESENSITIZING
AGENTS
DISCLOSING
AGENTS
DENTIRIFICES
Chlorhexidine
Flourides
Chlorhexidine
Triclosan
Potassium nitrate
Fluoride
Fluorescein
Two-tone dye
Erythrosine
Abrasive, detergents,
humectants, sweetening
agents, colouring agents

HORMONES RELATED DRUGS
BISPHOSPHONATES
VITAMIN D
HORMONES
REGULATING
CALCIUM
Vitamin C

VITAMIN C
• One of the important roles of vitamin C in metabolic function
is collagen synthesis particularly in the course of wound
healing.
• Relevant not only to periodontal tissues but also to formation
of bone matrix and maintenance of integrity of blood vessels.
• Alfano et al studied the effect of Ascorbic acid deficiency in
guinea pig periodontal tissues. This report indicated that
ascorbic acid deficiency increased the permeability of non
keratinized oral mucosal epithelium to bacterial endotoxin.
Mieko N et al. Dietary vitamin C and risk of periodontal disease J Periodontol 2000;71: 1215-1223.

• Alvares et al. compared PMN function between vitamin C
deficient monkeys and control group, and the deficient
group showed a significant reduction in chemotaxis and in
phagocytosis as compared to the controls.
Alvares et al. Effect of subclinical ascorbic deficiency on periodontal health in non-human primates. J Periodont Res 1981; 16:628-636.

VITAMIN D
• Calcitriol enhances absorption of calcium and phosphates from
intestines.
• It appears to help bone mineralization indirectly by maintaining
plasma calcium and phosphate level.
• No amount is synthesised in the body, a dietary allowance of
400 IU/day will prevent deficiency complications like retarded
development of mandible, faulty eruption of teeth, defective
tooth enamel, rickets in children and osteomalacia in adults.

BISPHOSPHONATES IN PERIODONTAL THERAPY
• YAFFE A et al (2003) found that in local drug delivery of
tetracycline in combination with alendronate showed
significant reduction in alveolar bone loss
• A R PRADEEP et al (2012)10,11 in two different studies
found significant reduction in PD and CAL and also more
percentage of bone fill after using 1 % of Alendronate gel in
the treatment of both chronic as well as aggressive
periodontitis.
Yaffe A , Herman A, Bahar H , and Binderman I .Combined local application of tetracycline and bisphosphonates reduces alveolar bone
resorption in rats.. Journal of Periodontology July 2003 vol 74, 1038-1042

• Bisphosphonates affect both bone resorption and deposition by
various mechanisms.
1. They bind to hydroxyapatite thus preventing its dissolution.
2. They inhibit osteoclast activation thus reducing the rate of
bone resorption.
3. They increase osteoblast differentiation thus aiding in bone
formation.
Yaffe A , Herman A, Bahar H , and Binderman I .Combined local application of tetracycline and bisphosphonates reduces alveolar bone resorption in rats..
Journal of Periodontology July 2003 vol 74, 1038-1042

PART – IV ( ON THE BASIS OF ADMINISTRATION )
C
O
N
T
E
N
T
S
• SYSTEMIC ADMINISTRATION
• LOCAL DRUG DELIVERY
• RECENT ADVANCES IN PERIODONTAL
MEDICINE

Chlorhexidine Chip - periochip
• A small chip that contains 2.5 mg of chlorhexidine gluconate in a
resorbable, biodegradable matrix of hydrolyzed gelatin that is cross-
linked with glutaraldehyde and packaged in individual foil containers.
• Indicated as an adjunct to SRP procedures for the reduction of pocket
depth.
• After placement, the chip has been reported to release chlorhexidine
into the gingival crevicular fluid (GCF) over 7 to 10 days.
Chlorhexidine is active against a broad range of microbes. It disrupts
the cell membrane and causes precipitation of the cytoplasm, resulting
in cell death.
• Does not require removal.

Doxycycline Gel – Atridox
• It is a subgingival, controlled-release delivery product composed of a
two-syringe mixing system.
• Syringe A contains 450 mg of a bio absorbable polymeric formulation
of 36.7% poly(d,l,-lactide) dissolved in 63.3% N-methyl-2-
pyrrolidone.
• Syringe B contains 50 mg of doxycycline hyclate
• Doxycycline is bacteriostatic, inhibiting bacterial protein .
• The gel has been reported to release doxycycline in the GCF over 7
days.
• The doxycycline gel is biodegradable and does not require removal.

Minocycline Microspheres - Arestin
• This contain the antibiotic minocycline hydrochloride
incorporated into a bioresorbable poly(glycolide-cod,l-lactide)
polymer in unit-dose cartridges.
• Its bacteriostatic, antimicrobial activity results from the
inhibition of protein biosynthesis.
• Each cartridge delivers minocycline hydrochloride equivalent
to 1 mg of minocycline free base.
• Indicated as an adjunct to SRP for the reduction of pocket
depth in patients with adult periodontitis.

• PerioCol-CG is a small, 10-mg
chip (4 × 5 × 0.25–0.32 mm)
designed as a collagen matrix
into which chlorhexidine
gluconate (2.5 mg) is
incorporated from a 20%
chlorhexidine solution.
• Designed for insertion into the
periodontal pocket and resorbs
after 30 days.
• 40% to 45% release in the first
24 hours, followed by a linear
release for 7 to 8 days.
• Chlo-Site is a xanthan gel,
consisting of a saccharide
polymer as a three-dimensional
mesh containing 1.5%
chlorhexidine in 0.5 mL of gel,
which is injected into the
periodontal pocket
• The gel contains two types of
chlorhexidine: a slow-release
chlorhexidine digluconate (0.5%)
and a rapid-release chlorhexidine
dihydrochloride (1.0%).
• The gel disappears from the
pocket in 10 to 30 days.
CHLORHEXIDINE BASED PRODUCTS
th

TETRACYCLINE BASED PRODUCTS
• PerioCol-TC - each vial contains
fish type I collagen impregnated
with approximately 2.0 mg of
tetracycline hydrochloride, which
is sterilized by gamma radiation
PerioCol-TC releases tetracycline
in vitro for 8 to 10 days.
• A periodontal dressing should be
placed to avoid dislodging the
fibers.
• It is indicated for the treatment of
adult periodontitis as an adjunct to
SRP for pockets more than 5 mm
deep.
• Periodontal Plus AB is a
bioresorbable tetracycline fiber. It
is 25 mg of pure fibrillar collagen
impregnated with approximately
2 mg of tetracycline
hydrochloride.
• The fiber biodegrades in the
periodontal pocket within 7 days.
• The fiber should be retained with
a periodontal dressing or covered
with a dental adhesive for 10
days.

DOXYCYCLINE BASED PRODUCTS
Ligosan Slow Release
• It is a 14% (w/w), resorbable doxycycline gel for
periodontal application.
• The product is used by inserting the cartridge into the
gun, opening the spray nozzle, and then discharging the
gel to the bottom of the pocket.
• Concentrations in the GCF remained above 16 µg/mL for
at least 12 days.
• Mechanical hygiene in the area should be avoided for 7
days

RECENT ADVANCES IN
PERIODONTAL
MEDICINE

Probiotics in the treatment of periodontitis
• Probiotics are available in the form of lozenges, tablets, cheese,
yogurt, rinses, capsules and liquid.
• Studies have been done regarding the beneficial effects of
probiotics on the patient with generalized chronic periodontitis
one such study done by Koll-Klais and co- workers stated that
there was a higher prevalence rate for L. fermentum in the oral
cavity of a healthy individual as compared to patients of
chronic periodontitis.
Recent advancement in periodontics. International journal of science and nature .vol.10 (1) 2019: 1-10

• In another study done by Riccia and co-workers, to find out
the anti-inflammatory role of Lactobacillus brevis in
periodontal disease, in the study they used lozenges of L.
brevis on patients of periodontitis for 4 days and observed a
difference in clinical parameters like bleeding on probing,
plaque index, gingival index which were markedly reduced.
• Zupancic et al. in their study incorporated autochthonous
bacteria a potential probiotics into nanofibers for local
treatment. The developed nanodelivery system for
administration into periodontal pockets, offers a promising
look out for the inhibition of periodontal pathogens with the
restoration of the healthy oral microbiota
Zupancic, S., Rijavec, T., Lapanje, A., Petelin, M., Kristl, J. and Kocbek, P. Nanofibers with Incorporated Autochthonous Bacteria as
Potential Probiotics for Local Treatment of Periodontal Disease Biomacromolecules, Just Accepted Manuscript.

Newer drugs for treatment of periodontal disease
• The use of newer drugs to resolve inflammation in periodontal
tissue like Resolvin. This drug lowers the recruitment of
neutrophils at the site of inflammation and also reduces the
number of cytokines and reactive oxygen species being produced
hence helps in reducing the inflammation.
• A new antibiotic study by Reed et al. named amixicile, a novel
inhibitor of pyruvate ferredoxin oxidoreductase. A minimal
inhibitory concentration ranging from 0.5–1.5µg/ ml inhibited
growth and other processes central to virulence in the in-vitro
study.
Reed, L.A., O’Bier, N.S., Oliver, L.D., Hoffman, P.S. & Marconi, R.T. (2018) Antimicrobial activity of amixicile against treponema
denticola and other oral spirochetes associated with periodontal disease. Journal of Periodontology

Drugs in periodontics

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