Drugs in perio

2. DR JEETHU JOHN JERRY
READER
MALABAR DENTAL COLLEGE AND RESEARCH CENTRE
DRUGS USED IN PERIODONTOLOGY

3. Contents:
1. Introduction
2. Chemicals used for Supragingival Plaque Control
3. Antibiotics Used in Periodontics
4. Systemic Administration of Antibiotics
5. Biologic implications
6. Local Delivery Of Antibiotics
7. Analgesics
8. Classes of Analgesics
9. Side effects of Strong Analgesics
10. Conclusion
11. References

4. Introduction
The fact that Mechanical therapy forms the base for Periodontal
Therapy is time tested. However, with updating evidence of
bacterial specificity in relation to aggressive forms of periodontitis
and also the difficulty in suppressing periodontal pathogens with
conventional therapy in certain cases has eventually led to the
development of antimicrobial and anti-inflammatory treatment
strategies. But total elimination of periodontal pathogens with drug
therapy alone may not be possible ,unless combined with
mechanical debridement.

5. Chemicals used for
Supragingival
Plaque Control

6. Phenols
• Exert a non-specific antibacterial action.
• Penetrate lipid component of the cell walls of gram
negative organisms.
• Cause structural damage thereby affecting the metabolic
processes that are dependent on enzymes contained
within the cell membranes.
• Exhibit anti-inflammatory activity as they inhibit
neutrophil Chemotaxis ,generation of Neutrophil

7. Only Moderately effective against oral Malodor and caused a
sustained reduction in levels of odorigenic bacteria.
(Pitts G et al 1983)
Short-term reductions in VSC after rinsing for four days
(Carvalho MD et al 2004)
When used as an adjunct to unsupervised oral hygiene, EO
provides an additional benefit with regard to plaque and
gingivitis reduction as compared to a placebo or control
(Judith 2007)

8. Quaternary Ammonium
Compounds
• They are surface active agents which carry a net negative
charge.
• Range of action predominantly Gram ‘+’ve organisms.
• They cause cell wall damage and subsequent leakage of
Cytoplasm by combining of cationic binding to the phosphate
group of the cell wall and disruption of the membrane integrity.

10. chlorhexidine
• Bisbiguanide family.
• MOA: Disruption of bacterial cell membrane.
• Significant effect on VSC
• Uses: adjunct in initial therapy
post-op management
handicapped patients
↓ plaque in drug induced overgrowth,
medically compromised patients
prophylactic

11. Chlorhexidine was superior to Listerine in its ability to maintain low plaque
scores and gingival health during this 3-week period of no mechanical oral
hygiene.
(Brecks 1990)
The most effective Antiplaque and antigingivitis agent.
( Bollen et el 1996, Bosy et al 1994, Addy M et al 1997,Jones et al 1997)
0.2% Chlorhexidine regimen reduced 43% reduction in VSC values and
greater than 50% reduction in organoleptic Rating.
(Rosenberg et al 1991)
Morning Halitosis reduced by 90%.
(van Steenberghe et al ,Spain 2001)

12. ANTIBIOTICS USED IN PERIODONTICS
• DEFINITION
• An Antibiotic is a naturally occurring, semisynthetic ,or
synthetic type of anti-infective agent that destroys or
inhibits the growth of selective microorganisms,
generally at low concentrations.

13. Systemic administration –
• When mechanical therapy alone is ineffective
• e.g., refractory periodontitis, periodontitis as a
manifestation of systemic diseases
• Local administration –
• Directly in the pocket
• Provide greater concentration directly to the infected area
• Reduced systemic side effects

14. SYSTEMIC ADMINISTRATION OF ANTIBIOTICS
Background and Rationale
• The treatment of periodontal disease is based on the infectious
nature of the disease. An ideal antibiotic for use in prevention and
treatment of periodontal disease should be specific for periodontal
pathogens ,allogenic and nontoxic , substantive, not in general use of
other diseases and inexpensive.
• The treatment of patient should be based on the patient’s clinical
status ,nature of colonizing bacteria and risk and benifits associated
with the proposed treatment plan

15. Common adverse Reactions of Antibiotics
• Allergic/anaphylactic reaction
• Superinfections of opportunistic bacteria
• Development of resistant bacteria
• Interactions with other medications
• Stomach upset
• Nausea & vomiting

16. Biological Implications
• The clinical diagnosis and situation dictate the need for possible
antibiotic therapy as an adjunct in controlling active periodontal
disease. The patient diagnosis can change over a period of time.
• Continuing disease activity, as measured by continuing attachment
loss ,purulent exudate, and continuing periodontal pockets of 5mm
or greater that bleed on probing is an indication of need for
periodontal intervention.
• Antibiotics for the periodontal disease are selected on the patient’s
medical and dental status, current medications and results of
microbial analysis if performed.
• Anti-infective agents can be used for enhancing regenerative healing

17. Tetracyclines - Introduction
• One of the most commonly used antibiotic in treatment of
periodontal diseases
• Frequently used in treatment of refractory periodontitis,
including localized aggressive periodontitis.
• Ability to concentrate in periodontal tissues & inhibit the
growth of Aggregatibacter actinomycetemcomitans.
• Anticollagenase effect – inhibit tissue destruction & aid in
bone regeneration.

18. Tetracyclines - Pharmacology
• Derived naturally from certain species of Streptomyces
• Bacteriostatic
• More effective against gram positive than gram negative
bacteria
• Concentration in gingival crevice 2-10 times that in serum
• Very effective against rapidly growing periopathogens at
low gingival crevicular fluid concentration.

19. Tetracyclines – Clinical Use
• As adjuncts in the treatment of localized aggressive
periodontitis. [A.a comitans in conjunction with SRP].
(Walker CB 1993)
• Combination of metronidazole & amoxicillin is preferred in
cases of increased resistance to tetracyclines
Concentration is 2-10 times more in GCF than Serum .
(Alger et al 1990,Bader et al 1985,Gordon et al 1991 )
Exert Anticollagenase effect that can inhibit tissue destruction and may aid in
bone regeneration. (Caton JG 2000,Lee HM 2004,Walker C 1998)

20. Tetracyclines – Specific Agents
Tetracycline
• Inexpensive
• Dosage: 250 mg four times a day
• Reduced patient’s compliance because of 4 capsules per
day
• Renal toxicity

21. Tetracyclines – Specific Agents
Minocycline
• Effective against broad spectrum of microorganisms
including spirochetes & motile rods
• Twice daily dose – increased patient’s compliance
• Less phototoxicity & renal toxicity than tetracycline
• Increased risk of reversible vertigo

22. Tetracyclines – Specific Agents
Doxycycline
• As effective as minocycline
• Once daily dose
• Good GI absorption
• Anti-infective dosage – 100 mg twice daily then 100 mg
once daily
22

23. Metronidazole - Introduction
• Nitroimidazole compound
• Developed in France to treat protozoal infections

24. Metronidazole - Pharmacology
• Bactericidal to anaerobic organisms
• Disrupts bacterial deoxy-ribo-nucleic acid synthesis
• Effective against A.a comitans when combined with other
antibiotics (Rams TE 1992)
• Also effective against P. gingivalis & P. intermedia.
(Greenstein G 1992)

25. Metronidazole – Clinical Use
• Treatment of Necrotizing ulcerative gingivitis, chronic &
aggressive periodontitis. (Lozdan J 1971).
• It is used as Monotherapy and used with root planning and
surgery.
• Recommended dose – 250 mg three times daily for 7 days
• When combined with amoxicillin or amoxicillin-clavulanate
potassium, useful in the management of Localized
aggressive periodontitis & refractory periodontitis

26. Metronidazole – Side Effects
• Antabuse effect in alcoholics – Disulfiram like reaction.
• Inhibits warfarin metabolism – increases Prothrombin time
• Interactions with lithium

27. Penicillins - Pharmacology
• Natural & semisynthetic derivatives of fungus Penicillium.
• Bactericidal
• Mode of action – inhibition of bacterial cell wall synthesis

28. Penicillins – Side Effects
• Allergic reactions
• Bacterial resistance
• GI disturbances
10%

29. Penicillins – Specific Agents
Amoxicillin
• Extended spectrum penicillin
• Effective against both gram positive & gram negative bacteria
• Excellent oral absorption
• Susceptible to penicillinase
• Useful in management of Localized and generalized aggressive
periodontitis.
• Dosage:500 milligram tid for 8 days. (Jorgensen MG 2000 :
Responsible use of antibiotics in Periodontics).

30. Penicillins – Specific Agents
Amoxicillin – Clavulanate Potassium
• Resistant to penicillinase producing bacteria
• Useful in the management of localized aggressive
periodontitis & refractory periodontitis.
(Offenbacher S et al 1987)

31. Clindamycin - Pharmacology
• Effective against anaerobic organisms and has strong affinity for osseous tissue. (Tyler K et al 1985 )
• Effective for patients allergic to penicillin
Clinical Use
• Periodontitis refractory to tetracycline therapy..
(Walker et al 1996;Jeffrey Gordon et al 1990).
• Recommended regimen – 300 mg twice daily for 8 days

32. Clindamycin – Side Effects
• Pseudomembranous colitis
• Diarrhea
Indicates colitis Discontinue drug
• Cramping

33. Cephalosporins - Pharmacology
• Action & structure similar to penicillins
• Resistant to a number of β-lactamases normally active
against penicillin

34. Cephalosporins – Clinical Use
• Not often used to treat dental infections
• Inferior to penicillins in their range of action against
periopathogens

35. Cephalosporins – Side Effects
• Rashes
• Urticaria
• Fever
• Gastro intestinal upset

36. Ciprofloxacin - Pharmacology
• Quinolone
• Effective against gram negative rods, including all
facultative & some anaerobic putative periodontal
pathogens
• Dosage: 500 mg twice daily for 8 days

37. Ciprofloxacin – Clinical Use
Minimal effect on Streptococcus species
Establish microflora associated with periodontal health
Only antibiotic in periodontal therapy effective against all
strains of A.a comitans. (Rams TE 1992)

38. Ciprofloxacin – Side Effects
• Nausea
• Headache
• Metallic taste in the mouth
• Abdominal discomfort (TZ).

39. Macrolides - Pharmacology
• Inhibit protein synthesis by binding to 50S ribosomal
subunits of microorganisms
• Bacteriostatic or bactericidal, depending on concentration
of drug
• Macrolides used for periodontal treatment –
• Erythromycin
• Spiramycin
• Azithromycin

40. Macrolides – Clinical Use
Erythromycin
• Does not concentrate in gingival crevicular fluid.
• Ineffective against most periodontal pathogens
• Not recommended as an adjunct to periodontal therapy

41. Macrolides – Clinical Use
Spiramycin
• Active against gram positive organisms
• Excreted in high concentrations in saliva
• Used as an adjunct to periodontal therapy in some
countries.

42. Macrolides – Clinical Use
Azithromycin
• Concentration in periodontal lesion > normal gingiva
• Penetrates fibroblasts & phagocytes in concentrations 100-
200 times greater than that of extracellular compartment
• Dose – loading dose of 500 mg followed by 250 mg/day for
5 days or 500 mg once daily for 4-7 days
( Schneider et al 1995,Blandizzi et aal 1999)

43. Local Drug Delivery
Of
Antibiotics

44. LIST OF VARIOUS COMMERCIALLY AVAILABLE LDD FORMS
Actisite Non resorbable
Periodontal plus AB Tetracycline Resorbable

45. Tetracycline-Containing Fibers
• Ethylene/vinyl acetate copolymer fiber (0.5 mm diameter)
containing 12.7 mg tetracycline across 9 inches.
• Sustained tetracycline concentration exceeding 1300µg/ml
for 10 days
• Reduce probing depth, bleeding on probing &
periopathogens
• Disadvantages:
• Time consuming
• Technique sensitive
• Second appointment for fiber removal.

46. Subgingival Doxycycline
Atridox
• 10% doxycycline gel in a syringe
• Only local drug delivery system approved by American
Dental Association
• Gain in Clinical attachment level & reduction in probing
depth & bleeding on probing
• Transient increase in resistance in oral microbes & no
overgrowth of foreign pathogens

47. Subgingival Minocycline
Arestin
• 2% minocycline encapsulated into bioresorbable
microspheres in a gel carrier
• Scaling & root planing + minocycline – better than Scaling &
root planing + placebo in terms of – clinical attachment
level, Probing depth. (Lu HK et al-2005, JPR).
• Reduce levels of Porphyromonas gingivalis, Prevotella
intermedia & Aggregatibacter actinomycetemcomitans

48. Subgingival Metronidazole
• 25% metronidazole gel
• Composition: glyceryl mono - oleate
sesame oil
• Applied in viscous consistency to pocket, where it is
liquidized by body heat & then hardens again

49. ANALGESICS

50. • DEFINITION: A drug that selectively relieves pain by acting on CNS
or peripheral pain mechanism, without significantly altering
consciousness
• Analgesics are common pain relievers.
• Many analgesics also have antipyretic properties as well. They can
be used to reduce fever
• Some analgesics are anti-inflammatory drugs as well.

51. CLASSES OF ANALGESIC DRUGS
NON OPIOD TYPE OF
ANALGESICS(mild analgesics)
Salicylates
-aspirin
-diflunisal
Other NSAIDs
-ibuprofen
-ketrolac
Acetaminophen
OPIOID TYPE OF ANALGESICS
(strong analgesics)
Natural opium alkaloid
Morphine,codeine
 Semisynthetic Heroin
and pholcodeine
Synthetic opioids
Pethidine
fentanyl

52. NON OPIOID TYPE OF
ANALGESIC
Aspirin
• Aspirin is believed to inhibit the enzyme Prostaglandin synthase which is
formed at the site of an injury.
• This inhibits the production of prostaglandins which produce fever and
swelling as well as transmitting pain signals to the brain.

53. Acetaminophen
• Acetaminophen is a pain reducer, such as Tylenol but does not
reduce inflammation
• It can be used efficiently in controlling postoperative pain
after open flap debridement in patients with bleeding
tendency.
• Overuse and overdoses can lead to acute liver failure and
kidney damage

54. Ibuprofen
• Ibuprofen is a more powerful pain reliever than aspirin in
high doses.
• It helps to relieve both pain and inflamation of the gums
• Side effects include gastrointestinal bleeding and irritation

55. Flurbiprofen
•Inhibits cyclooxygenase
•Inhibits neutrophil migration, reduces vascular
permeability & inhibits platelet aggregation
•Inhibits radiographic alveolar bone loss
•Increases anticollagenase effect of doxycycline when
combined

56. OPIOID TYPE OF ANALGESICS
Morphine
 Naturally occurring in poppy, Only needs to be isolated
 Very strong pain reliever but also very addictive (2nd to Heroin)
 Usually injected but can be smoked, sniffed or swallowed
 Morphine treatment reduced fiber attachment and alveolar
bone loss without affecting the increased leukocyte count in
gingivae. (Pacheco CM et al. 2007 )

57. • Most commonly used strong analgesic
• Similar to Morphine except for the replacement of a (OH-)
group for (OCH3) group
• Commonly used with Tylenol as a more mild analgesic
• 1/6 as strong as Morphine and less addictive.
Codeine

58. Synthetic opioids
• The active area of morphine has been identified and can be
synthesized.
• This has produced many synthetic analgesics and has allowed
scientists to eliminate some of the harmful side effects of more
natural analgesics.
• Pethidine,Fentanyl.

59. Mechanism of Strong
Analgesics
• The human body contains “natural opiates” in the brain
called endorphins
• These are produced in the body during extreme conditions
such as “running high” and extreme injuries.
• When these are absorbed by receptors in the brain the
body feels analgesia and the pain is reduced.
• Opiates derived from the poppy act in same way as
endorphins ,the “high” is produced because the
absorption is quicker than endorphins.

60. Side Effects of Strong Analgesics
Short term
• Dulling of Pain
• Euphoria
• Slow Nervous system
• Overdoses can lead to death
• Possibility of stroke
• Overall slowdown of
biological systems
Long Term
• Addiction and very strong
withdrawal effects
• Constipation
• Disruptions in menstruation
• “Cross-tolerance”
• Loss of appetite

61. To ConcludeLocal and Systemic Drugs have been used effectively in the
management of periodontal infections. The effectiveness of
mechanical debridement of plaque and repeated topical and systemic
administration of antibacterial agents are limited due to the lack of
accessibility to periodontopathic organisms in the periodontal pocket.
Systemic administration of drugs leads to therapeutic concentrations
at the site of infection, but for short periods of time, forcing repeated
dosing for longer periods.

62. References
 Clinical periodontology- 8th/ 10th /11th edition- Newman MG, Carranza FA.
 Essentials of medical pharmacology- 4th edition- Tripathi KD.
 Ciancio S G: Systemic medications: Clinical significance in periodontics. J
Clin Periodontol 2002; 29 (Suppl 2): 17–21.
 Walker C, Karpinia K: review- Rationale for use of antibiotics in periodontics.
J Periodontol 2002;73:1188-1196.
 Vicky Kaplish et al Pharmacophore 2013, Vol. 4 (2), 39-49; ISSN 2229 –
5402.

63. Haffajee AD, Socransky SS, Gunsolly JC: Systemic anti-infective periodontal
therapy. A systematic review. Ann Periodontol 2003;8:115-181
Antibiotics and chemoprophylaxis: Robin A. Seymour & Stephen D. Hogg
Periodontology 2000, Vol. 46, 2008, 80–108
Kenneth S. Control Released Local delivery Antimicrobials in periodontics.
Prospects for the future. JP 1993: 64, 782-791
The pharmacological basis of therapeutics, 10th edition- Goodman & Gilman
Pharmacology and therapeutics for dentistry, 5th edition- Yagiela, Dowd, Neidle
Essentials of pharmacology for dentistry- K.D. Tripathi
 Brennan MT, Wynn L R, and Miller C S, Charlotte. Aspirin and bleeding in
dentistry: an update and recommendations.Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 2007; 104:316-23

64.  Therapeutic Uses Of Non-Steroidal Anti-Inflammatory Drugs In Dentistry-
Raymond A. Dionne, Charles W. Berthold (critical review oral bio. Med. 2001;
12; 315)
 Periodontology 2000, Vol. 46, 2008, 143–164
 Periodontology 2000, Vol. 48, 2008, 92–110
 Modulation of the Host Response in Periodontal Therapy,
 J Periodontol 2002;73:460-470

65. ©M. S. Ramaiah University of Applied Sciences
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