1. 1. CONTENTS Introduction History Terminology of agents Ideal properties of antiplaque agents Criteria for usage of antimicrobials Approaches to chemical plaque control Chemical plaque control agents Conclusion References
2. 2. INTRODUCTION Plaque control is the regular removal of dental plaque and the prevention of its accumulation on the teeth and adjacent gingival surfaces.
3. 3. METHODS OF PLAQUE CONTROL Mechanical Chemical
4. 4. CHEMICAL PLAQUE CONTROL Inhibition of plaque development Elimination of existing plaque Inhibition of calcification of plaque Inhibition of microbial colonization on tooth surfaces
5. 5. History Ebers Papyrus 1500 BC: recipes for tooth powders and mouthrinses 2700 BC: mouth should be rinsed with childs urine; found in European writings beer, wine, honey, alum, vinegar
6. 6. Hippocrates 400B.C. dentrifice. W. D. Miller, 1890 chemoparasitic theory. Sodium, potassium salts
7. 7. TERMINOLOGY OF AGENTS European Federation of Periodontology in the 1996 European Workshop on Periodontology recommended Antimicrobial agents: chemicals that have a bacteriostatic or bactericidal effect in vitro that alone cannot be extrapolated to a proven efficacy in vivo against plaque. Plaque reducing/inhibitory agents: chemicals that have only been shown to reduce the quantity and/ or affect the quality of plaque, which may or may not be sufficient to influence gingivitis and/or caries.
8. 8. Antiplaque agents: chemicals that have an effect on plaque sufficient to inhibit gingivitis and/or caries Antigingivitis agents: chemicals which reduce gingival inflammation without necessarily influencing bacterial plaque (includes anti-inflammatory agents).
9. 9. IDEAL PROPERTIES 1. Eliminate pathogenic bacteria only. 2. Prevent development of resistant bacteria 3. Exhibit substantivity 4. Safe to the oral tissues at the conc and dosage recommended. 5. plaque and gingivitis. 6. Inhibit calcification of plaque. ( Bral and Brownstein 1988)
10. 10. 7. Do not stain teeth or alter taste. 8. No adverse effects. 9. Easy to use. 10. Inexpensive.
11. 11. CRITERIA FOR USAGE OF ANTIMICROBIALS Substantivity: The ability of an agent to be bound to the pellicle and tooth surface and to be released over an extended period of time with the retention of its potency minimal inhibitory concentration or substantivity assay
12. 12. pH and ion binding : ionic interactions between agent & receptor sites retention of agent. pH of delivery vehicle state of ionization of both agent & receptor site. Retention at low pH due to ionization of acid receptor groups (carboxylate, phosphate & sulfate). Bonesvol et al 1974
13. 13. Stability : chemical breakdown or modification may occur during storage, especially at elevated temperatures. Due to intrinsic instability of agent presence of other formulation excipients
14. 14. Penetrability : For a drug to be effective, it must be able to penetrate deep into the formed plaque matrix. Toxic safety : any agent used for prevention or treatment of oral diseases must have low toxicity.
15. 15. APPROACHES TO CHEMICAL SUPRAGINGIVAL PLAQUE CONTROL 1] Antiadhesive agents 2] Antimicrobial agents 3] Plaque removal agents 4] Antipathogenic agents [Addy and Moran 1997]
16. 16. Antiadhesive agents Pellicle surface to prevent the initial attachment of the primary plaque-forming bacteria. Antifouling agents Eg. Anionic polymers, substituted amino-alcohols, polymethylsiloxane. too toxic or ineffective against dental plaques
17. 17. Antimicrobial agents Inhibit plaque formation 2 mechanisms: Bacteriostatic Bacteriocidal Eg. Chlorhexidine
18. 18. Plaque removal agents Chemical toothbrush Eg: hypochlorites, enzymes Kornman 1986
19. 19. Antipathogenic agents Direct approaches to alter plaque ecology to a less pathogenic flora are restricted and have not yet led to the development of agents appropriate for clinical use [Cummins, 1992] Theoretically, all antimicrobial agents have the potential to disturb the ecological balance of dental plaque
20. 20. Bacterial succession plaque formation
21. 21. CHEMICAL PLAQUE CONTROL AGENTS Based on antimicrobial activity & substantivity Kornman 1986CHEMICAL PLAQUE CONTROL AGENTS FIRST GENERATION Eg: antibiotics, phenol,quarternary ammonium compounds & sanguinar SECOND GENERATION Eg: Bisbiguanides,(chlorhexidine) THIRD GENERATION Eg: delmopinol
22. 22. Based on groups (Newburn)
23. 23. Systemic antimicrobials including antibiotics Bacterial nature of plaque Not be used either topically or systemically as preventive agents. Risk to benefit ratio is high. Bacterial resistance and hypersensitivity Addy, Kornman 1986
24. 24. Enzymes 1st group not truly antimicrobial agents, more plaque removal agents- potential to disrupt early plaque matrix, dislodging bacteria from the tooth surface. dextranase, mutanase, protease. poor substantivity, mucosal erosions.
25. 25. 2nd group enhance host defense mechanisms. Glucose oxidase, amyloglucosidase.
26. 26. Quarternary ammonium compounds Cationic surface active agents. Structure central nitrogen atom linked to 4 alkyl groups by covalent bonds. Net positive charge, reacts with negatively charged cell membrane phosphates. More effective against Gm-ve.
27. 27. Benzalconium chloride,cetylpyridinium chloride (0.05%) At oral pH monocationic, adsorb readily & quantitatively > CHX (Bonesvoll & Gjermo 1978) Low substantivity, 3-5 hours, loss of activity once adsorbed or rapid desorption. No added benefits. (Moran &Addy 1991)
28. 28. Phenols & essential oils Both plaque inhibitory & anti-inflammatory action due to anti-oxidative activity. Charles et al 2004, 6 month study, equivalent effects as CHX without side effects. pH is low (pH 4.3), erosion of dentine & enamel.
29. 29. Triclosan nonionic antimicrobial, trichlora-2-hydroxy phenyl ether. Simple solution, high conc 0.2%, dose (20mg twice/day) moderate plaque inhibitory action substantivity of 5 hours. Activity zinc citrate, co-polymer polyvinylmethyl ether maleic acid. Jackson 1997 > gingivitis compared to plaque reductions anti-inflammatory.
30. 30. Listerine - thymol, eucalyptol, methyl salicylate, benzoic acid, boric acid in a hydroalcoholic base. Effective inhibitor of plaque formation, development of gingivitis. High conc- cell wall disruption Low conc- inhibition of bacterial enzymes
31. 31. Siegrist et al no effect. Axelsson & Lindhe with mechanical control. Positive effect. Long term trials efficacy of Listerine is confirmed. (Lamster et al, 1983)
32. 32. Natural products Sanguinarine Benzophenathridine alkaloid derived from sanguinaria canadensis. Structurally related to alkaloids. precancerous lesions upto ten folds, even after cessation. Tea tree oil gingival inflammation Sookoulis & Hirsch 2004
33. 33. Metal salts Copper, Tin, Zinc Metal salt used, conc, frequency of use. Polyvalent metal salts high conc, effective Stannous fluoride difficult to formulate, hydrolysis in water Metal salts + antiseptics
34. 34. Oxygenating agents Disinfectants Hydrogen peroxide supragingival plaque control. Peroxyborate acute ulcerative gingivitis. (Wade 1966) Cleansing action- effervescence Undesirable tissue changes
35. 35. Detergents Sodium lauryl sulfate. Antimicrobial activity. Plaque inhibitory action. Moderate substantivity 5-7 hours. Not used alone.
36. 36. Amine alcohols antimicrobial or antiseptic. Morpholinoethenol derivatives- Octopinol antiplaque. Delmopinol 0.1%, 0.2 %. (Collaert et al, 1992) MOA interference with plaque matrix formation, adherance of plaque forming bacteria
37. 37. Chlorhexidine Developed in 1940s by Imperial Chemical Industries, England Marketed in 1954 as antiseptic for skin wounds Dentistry- Initially used for presurgical disinfection of mouth & in Endodontics 1st definitive study (Loe & Schiott 1970)
38. 38. 3 forms digluconate & acetate water soluble hydrochloride sparingly soluble
39. 39. Mechanism of action Dicationic nature ( 2 +ve charges on either side of hexamethylene bridge) extremely interactive with anions Relevant to its efficacy, local side effects, safety & difficulty in formulation with other products Spectrum wide range of Gm+ve & Gm-ve bacteria, some fungi, yeasts & certain viruses like HBV & HIV (Wade & Addy, 1989)
40. 40. Binds strongly to bacterial cell membrane Low Conc. permeability leakage, potassium. High Conc Ppt bacterial cytoplasm Death Readily absorbs to pellicle Persistent bacteriostatic action lasting > 12 hrs. (Schiott et al 1970) Attaches to pellicle with one cation , the other free to interact with bacteria trying to colonize. (Jenkins, 1988)
41. 41. Anionic substances, plaque inhibition effect of CHX, if used shortly after rinses with the antiseptic. (Barkvoll et al 1989) Slow release from surfaces prolonged antibacterial effect.
42. 42. Toxicology, safety & side effects Brown discoloration of teeth, restorations & dorsum of tongue Taste disturbance (Salt) Lang et al 1988 Oral mucosal erosions Unilateral/Bilateral Parotid swelling Increased supragingival calculus formation ppt of proteins, pellicle thickness, inorganic salts. Bitter taste.
43. 43. The mechanisms proposed for chlorhexidine staining 1. Degradation of the chlorhexidine molecule to release parachloraniline. 2. Catalysis of Maillard reactions. 3. Protein denaturation with metal sulfide formation. 4. Precipitation of anionic dietary chromogens. (Eriksen et al. 1985, Addy & Moran 1995, Watts & Addy 2001)
44. 44. Anti-discoloration system (ADS) was launched=Europe A clinical study supporting to show reduced staining had significant drawbacks in design and presentation (Bernadi et al. 2004). A laboratory study found no difference in staining potential (Addy et al. 2005) plaque regrowth study showed significantly reduced plaque inhibition for the ADS rinse (Arweiler et al. 2006). If it does not stain it does not work.
45. 45. The antibacterial mode of action of chlorhexidine The bacterial cell is characteristically negatively charged. The cationic chlorhexidine molecule is rapidly attracted to the negatively charged bacterial cell surface, phosphate-containing compounds. This alters the integrity of the bacterial cell membrane and chlorhexidine is attracted towards the inner cell membrane. Chlorhexidine binds to phospholipids in the inner membrane, leading to increased permeability of the inner membrane and leakage of low- molecular weight components, such as potassium ions
46. 46. Antiplaque effect Any bacteria adhering to the tooth surface are challenged by the chlorhexidine at the surface. Depending on the bacterial species, and the amount of chlorhexidine attached to the tooth surface, these microorganisms are either killed (bactericidal effect) or are simply prevented from multiplying (bacteriostatic effect).
47. 47. The influence of the bacteriostatic effect will increase over time as the concentration of chlorhexidine at the tooth surface decreases, due to desorption into bacteria, saliva etc. Plaque is prevented from forming because the bacteria attaching to the tooth surface cannot multiply. The persistent, bacteriostatic effect of chlorhexidine is what makes chlorhexidine the gold standard
48. 48. Delivery system Tooth paste Mouth rinse Gel Sprays Varnishes Slow release vehicles
49. 49. Clinical uses Plaque inhibition as an adjunct to mechanical therapy & professional prophylaxis. Following oral surgical procedures Intermaxillary fixation Physically/Mentally Handicapped Medically compromised
50. 50. Recurrent oral ulcers Orthodontic appliance Subgingival irrigation. Denture stomatitis Preoperative rinse Oral malodor High-risk caries patients
51. 51. Povidine iodine 1811, Bernard Courtois Iodine 1880, Devaine Bactericidal efficacy Late 1960s Povidine iodine
52. 52. Structure of Povidine-iodine (PVP-I): Iodophor (Iodine + Polyvinyl pyrrolidone {Povidine}) 10% of bound iodine PVP-I conc/ 10 ability to dissolve in water & alcohol irritability & staining
53. 53. Spectrum & mechanism of Microbial destruction G+ve, G-ve, fungi, mycobacteria, viruses & protozoans Bacterial activity Amino (NH-), thiol (SH-), phenolic hydroxy (OH-) Schreier et al- Transient / permanent pore formation loss of cytoplasmic material & deactivation of enzymes Coagulation of nuclear material
54. 54. In vitro study, all tested strains susceptible to PVP-I applied for 120 sec Bactericidal effect- low conc (0.1-1%)
55. 55. Caufield et al
56. 56. Side effects Staining teeth/ tissues thyroid dysfunction: short-term Long-term Allergic to iodine Pregnant & lactating mother
57. 57. Should antiplaque agents be only used as adjuncts to mechanical cleaning? Which vehicle? Which chemical?
58. 58. CONCLUSION Plaque control is one of the key elements of the practice in dentistry
59. 59. References Newman MG, Takei HH, Klokkevold PR, Carranza FA. 10th edition. Carranzas Clinical Periodontology. Saunders Company 2006. 579-601 Clinical periodontology and Implant dentistry, 5th edition, Jan Lindhe. Strategies and agents in supragingival I chemical plaque control MICHELB RECX. Periodontology 2000, Vol. 15, 1997, 100-108
60. 60. Chemical plaque control- prevention for the masses JOHN M. MORAN. Periodontology 2000, Vol. 15, 1997, 109-117