Rationale for the use of antibiotics:-

The scholastic contention over the criticalness of a particular or non-particular bacterial etiology for periodontal ailments might never be completely determined. On the other hand, there is little uncertainty that certain particular organic entities are nearly connected with a few manifestations of periodontal sickness. ^[15] Dissimilar to the lion's share of general diseases, all the suspected periodontal pathogens are indigenous to the oral greenery. ^[16,
17]Thusly, the long haul and aggregate disposal of these creatures with anti-infective agents will be extremely hard to accomplish as quick repopulation with the indigenous microorganisms will happen when the help is finished. ^[18] By and by, in specific types of periodontitis the loss of connective tissue connection is quick. Amazingly destructive, gram - negative organic entities populate the profound pockets, and microscopic organisms can really attack the connective tissue. ^{[19, 20]} Under these circumstances, anti-infective give a valuable assistant to root planing, which independent from anyone else may not uproot all subgingival stores and positively would not influence any attacking living beings that had officially entered the delicate tissue.

Routes of administration:-

The particular point of utilizing anti-infective agents as a piece of the treatment regimen is to accomplish, inside the periodontal environment, a convergance of the medication that is sufficient either to slaughter or capture development of the pathogenic microorganisms. The best and solid system for attaining these fixations is by systemic organization, whereby the medication has the capacity bathe the subgingival verdure by passing into the ginival crevicular liquid. ^[21] In reality, certain medications, for example, tetracycline have been found to pack in crevicular liquid at larger amounts than those found in serum after the same oral measurements. ^[22] The medication can then tie to the tooth surface, from which it is discharged in dynamic form. ^[23]Anti-infective agents can be managed provincially (prompt or controlled discharge) or systemically. Systemically directed anti-infective agents infiltrate the periodontal tissues and the pocket through serum. There they can achieve the microorganisms which are blocked off to scaling instruments and neighborhood anti-toxin treatment. Systemic anti-infective help additionally can possibly stifle any periodontal pathogenic microbes colonizing the profound fissure of the tongue and clinically non-sick locales that could conceivably cause constant reinfection. ^[24] Systemic anti-infective help is along these lines profitable for the annihilation and aversion of diseases by periodontal pathogenic microscopic organisms that attack the subepithelial periodontal tissues or that colonize extradental regions. In choosing whether to utilize remedial systemic anti-infective treatment, it is essential to consider the potential profits and symptoms. The profits may permit treatment of patients who have had constrained reaction to customary mechanical help and those with various unhealthy destinations displaying hard-headed periodontitis. The potential dangers incorporate advancement of safe bacterial species, rise of contagious deft contaminations or Pseudomonas disease, and hypersensitive responses. ^[25,26]

A few studies have assessed the utilization of anti-invectives to stop or diminish the movement of periodontitis. ^[27-30] Systemically regulated anti-infective agents demonstrate a measurably altogether more prominent addition in connection and decrease inside and out of periodontal pockets, paying little mind to starting examining systems or remedial modalities (anti-infective help alone, in conjunction with scaling and root planing, or in conjunction with scaling and root planing in addition to surgical treatment).

Patients who are prone to profit from anti-infection agents are those for whom traditional mechanical treatment has demonstrated insufficient (i.e., those with stubborn periodontitis), those torment from intense periodontal diseases (necrotizing periodontal illness and periodontal abscesses) or forceful periodontitis, and certain medicinally traded off patients. ^[31]Patients who smoke can likewise profit from systemic anti-infective treatment in conjunction with traditional mechanical treatment. ^[27] Moreover, periodontitis brought about by A. actinomycetemcomitans frequently obliges anti-infective treatment on the grounds that this bacterium is found on all mucous layer surfaces of the oral depression ^[32], and is equipped for attacking all delicate tissues. ^[33] This bacterium can accordingly rapidly recolonize the periodontal pocket after mechanical help without anti-infective agents. ^[34]

Choice of antibiotics:-

The decision of anti-toxin in clinical practice may be focused around microbiological dissection of the specimens got from influenced destinations. ^[31] All the more frequently, hence, the decision of anti-infection is exact and focused around the clinical signs. Systemic anti-infective help for periodontal treatment typically includes immunotherapy focused around metronidazole, tetracycline’s (tetracycline, doxycycline, minocycline), clindamycin, ciprofloxacin and the β-lactams (amoxicillin with or without clavulanic acid). ^[30]

Metronidazole:-

Metronidazole is a nitroimidazole compound with a wide range of action against protozoa and anaerobic microscopic organisms. ^[35] In medication, it is utilized as a part of the treatment of trichomonal genital contaminations, as a prophylactic executor before stomach surgery, and in the administration of extreme anaerobic diseases. ^{[36, 37]} The antibacterial movement against anaerobic cocci, anaerobic Gram - negative bacilli, and anaerobic Gram - positive bacilli had prompted its utilization in the treatment of periodontal sicknesses. ^[38]

In periodontal treatment, metronidazole has been utilized both as a part of tablet structures, and less regularly, as a topical application. The medication is decently ingested after oral organization and the top plasma level is generally arrived at in around one hour³⁹. The half-time of metronidazole is around 8 hours and the main site of digestion system is the liver. Metronidazole is excreted in urin.

Metronidazole is broadly circulated all through the body and, after an oral measurement, can be discovered in spit and crevicular liquid. ^[40] Following five days, oral dosing with 250mg thrice day by day, the levels of metronidazole in crevicular liquid demonstrate a much more prominent range and can be about half higher than the simultaneous serum focuses. ^[41]

The method of reasoning utilization of metronidazole in the treatment of periodontal infections and other oral contaminations has rotated around the drug's specificity for anaerobes and the obvious powerlessness of powerless living beings to create safety. ^{[42, 43]} In one of the first studies on metronidazole and periodontal malady^[44], a measurement of 250mg, thrice every day for one week was managed to five patients. This brought about noteworthy decreases in draining scores and pockets profundities, and additionally picks up in connection levels; what's more these enhancements were maintained six months after help. In three of the patients, mechanical debridement was embraced and this helped the change of the periodontal condition.

The clinical, histopathological, and bacteriological profit of metronidazole help is more professed when simultaneous scaling, root planing, and oral cleanliness direction are attempted.^[45] The seriousness of the periodontal devastation might thusly be a critical thought in the utilization of metronidazole. Progressed and recalcitrant periodontitis react well to the medication when it is utilized as an aide to conventional helpful measures. ^{[46, 47]} A problematical gathering of periodontal patients are those with cutting edge malady yet who don't react to oral cleanliness direction. The investigation of 10 such patients ^[48] demonstrated that a week's course of metronidazole brought about critical changes in pockets profundities and connection levels. They closed, then again, that these progressions, which happened without change in either plaque records or aggravated gingival units, were not of sufficient clinical size to warrant organization of a restoratively paramount medication. At last, metronidazole has likewise been discovered to be exceptionally successful, when consolidated with amoxicillin, in taking out A. a. in patients experiencing forceful periodontitis. ^[49] This lead to very nearly add up to disposal of the aggregatibacter for up to 11 months after treatment. ^[50] In a late study, Guerrero and others ^[51] plainly exhibited that the systemic organization of a consolidation of metronidazole and amoxicillin, in conjunction with nonsurgical treatment of forceful periodontitis, essentially enhanced clinical results for a time of six months. The oral measurement for metronidazole is 750mg/day, which is administrated as 250mg tablets at eight hourly interims for eight days aide to both nonsurgical and surgical treatment. The oral measurement for metronidazole in blending with amoxicillin is 750 mg/day (for each one medication) for eight days.

Clindamycin:-

Clindamycin is a derivate of lincomycin that is more dynamic and has fewer symptoms than the guardian drug. Clindamycin is viable against gram-positive cocci and gram-negative anaerobic bars, however has next to no effect on A.a. ^[66] Clindamycin is very nearly totally ingested after oral organization to create a crest blood focus in around 60 min. The half-life of the medication is around 3 hrs and it is decently circulated all through the tissues including bone. Clindamycin likewise gathers in polymorphonuclear leukocytes. The majority of the medication is metabolized and discharged in the pee and bile.

Because of the potential seriousness of reactions that can go hand in hand with the utilization of these medications, their utilization in the treatment of periodontal infection has been constrained. Short-term, clinical and microbiological studies have demonstrated that clindamycin is helpful in controlling progressed periodontal contaminations. ^{[67, 68]}This anti-infective is likewise viable in the treatment of hard-headed periodontitis. Be that as it may, clindamycin ought to be endorsed with alert due to the danger of abundance of Clostridium difficile, which could bring about pseudo membranous colitis. ^[31] The oral dosage for clindamycine is 900mg/day, which is administrated as 300mg tablets at eight-hourly interims for eight days subordinate to both non-surgical and surgical treatment.

Tetracycline’s (Doxycycline, Minocycline):-

The tetracycline’s are a gathering of nearly related, bacteriostatic anti-infective agents that give an "expansive range" of movement against both Gram-positive and Gram negative species, albeit more suitable anti-toxins are generally favored for Gram-positive contaminations. The tetracycline’s, including doxycycline and minocycline, are dynamic against paramount periodontal pathogens, for example, A. actinomycetemcomitans; they likewise have against collagenase properties and can diminish tissue pulverization and bone resorption. ^{[52,53, 54]}

Tetracyclines are generally given orally, albeit topical applications have been utilized as a part of periodontal treatment regimens. ^{[55, 56]} Tetracyclines are retained from the gastrointestinal tract and retention is diminished when the medications are brought with milk items or with substances containing calcium, magnesium, iron, or aluminum. On the other hand, actually when the medications are assumed an unfilled stomach, a certain sum stays in the insides. All tetracycline’s are appropriated generally in the tissues and are limited in creating dental structures and bone. Tetracycline, minocycline and doxycycline are perceivable in crevicular liquid after oral dosing and their separate focuses can achieve levels 10 times and five times in the serum. ^{[57, 58]}

Tetracycline is discharged in the pee and ought not to be given to patients whose renal capacity is traded off. Doxycycline is discharged overwhelmingly in the defecation and subsequently does not collect in the blood of patients with renal sickness. Discharge of minocycline is likewise unaffected by the condition of renal capacity as the medication seems, by all accounts, to be metabolized in the liver and after that discharged in the defecation.

Tetracycline has been indicated to be significant profit in the treatment of forceful periodontitis in which the prime pathogen, Aggregatibacter actinomycetemcomitans, is extremely helpless to the anti-infective. ^[59] This capnophilic, Gram-negative pole is hard to wipe out from forceful periodontitis patients by mechanical debridement alone^{[60, 61]}, probably as a result of its capacity to attack the delicate tissue. Systemic organization of 1g/day tetracycline for 3-6 weeks in conjuction with supragingival plaque control can stop the movement of the forceful periodontitis sores. ^{[62, 63]}

Notwithstanding the anti-infective impacts of tetracyclines, a further component has been proposed to clarify their viability in the treatment of periodontal sickness. In an arrangement of lab tests and clinical trials on diabetic people, Golub et al. have demonstrated that tetracycline, doxycycline, and minocycline can all stifle the action of the tissue catalyst collagenase as dictated by its vicinity in crevicular liquid. ^[64,
65]

The oral measurement for tetracycline is 1g/day, which is administrated as 250mg tablets at six-hourly interims for two weeks assistant to both non-surgical and surgical treatment. The oral dosage for the doxycycline and minocycline is 100-200mg/day, for 21 days.

Other antibiotics:-

Ciprofloxacin is successful against a few periodontal pathogens, including A. a. ^[70] This anti-infective successfully infiltrates the sick periodontal tissues and can achieve higher fixations in the crevicular liquid than in the serum. The β-lactams, including amoxicillin, are broad spectrum tranquilizes that are regularly recommended by periodontitis for treating periodontal abscesses. These anti-invectives show superb tissue dissemination yet moderately low focuses and are found in the crevicular liquid. ^[69]

Systemic phenoxymethylpenicillin has obviously been utilized effectively as a piece of a surgical regimen in the treatment of forceful periodontitis. ^[71] Nonetheless, later comes about because of a controlled clinical trial demonstrated that the adjunctive utilization of phenoxymethylpenicillin does not upgrade the treatment of forceful periodontitis by root planing and fold surgery. ^[72]

A few studies have been given to the systemic utilization of host - reaction modulator operators, for example, nonsteroidal calming medications^{[73, 74]}and subantimicrobial dosages of doxycycline. ^{[75, 76]}

Indications for antibiotics in periodontal therapy:-

The aftereffects of the clinical trials talked about above recommend that there is an essential part for anti-infective help as a subordinate to periodontal treatment. As per the general standards of recommending anti-invectives, then again, it is crucial that the medications are regulated just after cautious case determination, and anti-infective help ought to be a substitute for the routine and time-respected treatment regimens.

The accompanying periodontal infection states would legitimize the adjunctive utilization of anti-toxins:

1. In extreme cases both of intense necrotizing ulcerative gingivitis and periodontitis, particularly if there are indications of systemic inclusion, metronidazole can rapidly mitigate the side effects, which then allows through mechanical debridement to be completed.

2. Periodically, the neighborhood disease of a periodontal boil can spread inside tissue planes to cause checked facial swelling and systemic involvement. In these cases, expansive range anti-invectives ought to be endorsed to control the contamination. Cautious clinical and radiographic examinations must be carried out to build whether the injury is entirely periodontal in starting point or whether there is pupil contribution of the related teeth.

3. Different canker arrangement and horrible periodontal disease would require the organization of anti-toxins (metronidazole and tetracycline). Various therapeutic conditions (e.g. Diabetes mellitus) can incline to cutting edge periodontal demolition with canker shaping.

4. Anti-infective treatment is justified in instances of periodontal illness, which, regardless of through non-surgical administration and great plaque control, keep on showing breakdown and loss of attachment. These alleged stubborn cases can profit from a short course of anti-toxin help. The medication of decision ought to be dead set from testing the cultivable pocket verdure from which the dominating populating living beings can be distinguished.

5. Anti-infective help is suggested in the administration of instances of forceful periodontitis either in combo with fold surgery or a non-surgical treatment program.

Contraindications and unwanted effects:-

Anti-toxins are among the most generally endorsed pharmaceutical operators in cutting edge drug. Albeit just a little number of these medications have been utilized as a part of the treatment of periodontal maladies, it is vital that the principle contraindications for their use and their conceivable undesirable impacts are known to the periodontitis.^[66,67,68]

For the most part, the contraindications for utilization are identified with the disabled digestion system and discharge of the medications. Thusly, infection or weakened capacity of the hepatic or renal tracts ought to warrant alert in endorsing systemic anti-invectives. At the point when penicillin’s are endorsed it is fundamentally imperative to figure out if or not there is a history of touchiness to the medication. The undesirable impacts of penicillin are regularly gentle and portrayed by rashes, urticaria, joint agonies, and dermatitis, albeit extreme anaphylactic responses have been accounted for and can be lethal.^[77,78]

CONCLUSION:

Writing has demonstrated long haul profits of nonsurgical help in keeping up clinical connection levels, with and without systemic anti-invectives. However, those long haul victories rely on upon ideal oral cleanliness and standard upkeep visits for observing the status of periodontium and fortification of every day plaque evacuation by the patient. In the event that the patient does not assume sufficient liability for home mind and other consistence issues, backslide is liable to happen. In those cases, the circumstance supports the utilization of anti-infection agents as a helpful methodology.

Systemically managed anti-infection agents can achieve microorganisms that are unavailable to scaling instruments or nearby anti-infective help. The most every now and again utilized anti-invectives are metronidazole, the tetracyclines, clindamycin, ciprofloxacin and amoxicillin. At the point when choosing whether to utilize remedial systemic anti-toxin help, in any case, it is critical to consider both the profits and the undesirable impacts.

REFERENCES:

1. Pejcic A, Peševska S, Grigorov I, et al: Periodontitis as a Risk Factor for General Disorders. Acta Facult Med Naiss 23(1); 2006:59-65.

2. Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol 4(1); 1999:1–6.

3. Van Dyke TE, Sheilesh D. Risk factors for periodontitis. J Int Acad Periodontol 7(1); 2005:3-7.4.

4. Paster BJ, Boches SK, Galvin J et al. Bacterial diversity in human subgingival plaque. J Bacteriol 183(12); 2001:3770-83.9.

5. Nishihara T, Koseki T. Microbial etiology of periodontitis. Periodontol 2000 2004; 36:14–26.10.

6. Feng Z, Weinberg A. Role of bacteria in health and disease of periodontal tissues. Periodontol 2000 2006; 40:50-76.

7. Slots J, Ting M. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontol 2000 1999; 20:82–121.

8. Schenkein HA. Host responses in maintaining periodontal health and determining periodontal disease. Periodontol 2000 2006; 40:77-93

9. Kinane DF, Lappin DF. Clinical, pathological and immunological aspects of periodontal disease. Acta Odontol Scand 2001; 59(3):154-60.

10. Madianos PN, Bobetsis YA, Kinane DF. Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. J Clin Periodontol 2005; 32 (Suppl 6):57-71.

11. Sorsa T, Tjaderhane L, Salo T. Matrix metalloproteinases (MMPs) in oral diseases. Oral Dis 2004; 10 (6):311-8.

12. Reynolds JJ, Meikle MC. Mechanisms ofa connective tissue matrix destruction in periodontitis. Periodontol 2000 1997; 14:144-57.20.

13. Kaldahl, WB, Kalkwarf KL, Patil KD. A review of longitudinal studies that compared periodontal therapies. J Periodontol 1993; 64(4):243–53.

14. Kaldahl WB, Kalkwarf KL, Patil KD, et al. Long-term evaluation of periodontal therapy: I. Response to 4 therapeutic modalities. J Periodontol 1996; 67(2): 93-102.

15. Theilade E. The non-specific theory in microbialv aetiology of inflammatory periodontal diseases. J Clin Periodontol 1986; 13:905-11.

16. Zambon JJ, Christersson LA, Slots J. Actinobacillus actinomycetemcomitans in human periodontal disease. Prevalence in patients groups and distribution of biotypes and serotypes within families. J Periodontol 1983; 54:707-11.

17. Wolff LF, Liljemark WF, Bloomqvist CG, et al. The distribution of Actinobacillus actinomycetemcomitans in human plaque. J Perio Res 1985; 20:237-50.

18. Van Palenstein Heldermann WH. Is antibiotic therapy justified in the treatment of human chronic inflammatory periodontal disease? J Clin Periodontol 1986, 13:932-8.

19. Gillett R, Johnson NW. Bacterial invasion of the periodontium in a case of juvenile periodontitis. J Clin Periodontol 1982; 9:93-100.

20. Saglie R, Newman MG, Carranza FA, Pattison GL. Bacterial invasion of gingiva in advanced periodontitis in humans. J Periodontol 1982; 53: 217-22.

21. Herrera D, Alonso B, León R, Roldán S, Sanz M. Antimicrobial therapy in periodontitis: the use of systemic antimicrobials against the subgingival biofilm. J Clin Periodontol 2008; 35:45-66.

22. Baker PJ, Evans RT, Slots J, Genco RJ. Susceptibility of human oral anaerobic bacteria to antibiotics suitable for topical use. J Clin Periodontol 1985; 12:201-08.

23. Baker PJ, Evans RT, Coburn RA, et al. Tetracycline and its derivatives strongly bind to and are released from the tooth surface in active form. J Periodontol 1983; 54:580-5.

24. Slots J, Ting M. Systemic antibiotics in the treatment of periodontal disease. Periodontol 2000, 2002; 28: 106-76.

25. Drisko CH. Non-surgical pocket therapy: pharmacotherapeutics. Ann Periodontol 1996; 1(1):491-566.

26. Walker CB. The acquisition of antibiotic resistance in the periodontal microflora. Periodontol 2000 1996; 10:79-88.

27. Haffajee AD. Systemic antibiotics: to use or not to use in the treatment of periodontal infections. That is the question. J Clin Periodontol 2006; 33(5):359-61.

28. Herrera D, Sanz M, Jepsen S, et al. A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin Periodontol 2002; 29(Suppl 3):136- 59, discussion 160–2.

29. Haffajee AD, Socransky SS, Gunsolley JC. Systemic anti-infective periodontal therapy. A systematic review. Ann Periodontol 2003; 8(1):115-81.

30. Van Winkelhoff AJ, Rams TE, Slots J. Systemic antibiotic therapy in periodontitics. Periodontol 2000 1996; 10:45-78.

31. Slots J; Research, Science and Therapy Committee. Systemic antibiotics in periodontics. J Periodontol 2004; 75(11):1553–65.

32. Mombelli A, Gmur R, Gobbi C, et al. Actinobacillus actinomycetemcomitans in adult periodontitis. I. Topographic distribution before and after treatment. J Periodontol 1994; 65(9):820-6.

33. Meyer DH, Lippmann JE, Fives-Taylor PM. Invasion of epithelial cells by Actinobacillus actinomycetemcomitans: a dynamic, multistep process. Infect Immun 1996; 64(8):2988–97.

34. Van Winkelhoff AJ, Tijhof CJ, de Graaff J. Microbiological and clinical results of metronidazole plus amoxicillin therapy in Actinobacillus actinomycetemcomitans-associated periodontitis. J Periodontol 1992; 63(1):52-7.

35. Walker CB, Karpinia K, Baehni P. Chemotherapeutics: antibiotics and other antimicrobials. Periodontol 2000 2004; 36(1):146-65.

36. Stoltze K, Stellfeld M. Systemic absorption of metronidazole after application of a metronidazole 25% dental gel. J Clin Periodontol 1992; 19:693-7.

37. Roberts MC. Antibiotic toxicity, interactions and resistance development. Periodontol 2000 2002; 28:280-97.

38. Loesche WJ, Giordano JR, Hujoel P, et al. Metronidazole in periodontitis: reduced need for surgery. J Clin Periodontol 1992; 19(2):103–12.

39. Rood JP. The value of metronidazole in dental and oral surgery. Dental Update 1980; 7:293-300.

40. Altman EG. Rational use of metronidazole. Austral Dent J 1980; 25:135-8.

41. Giedrys-Lepeper E, Selipsky H, Williams BL. Effects of short-term administration of metronidazole on the subgingival microflora. J Clin Periodontol 1985; 12:797- 814.

42. Mitchell DA. Metronidazole: its use in clinical dentistry. J Clin Periodontol 1984; 11:145-58.

43. Heimdahl A, Nord CE,Okuda K. Effect of tinidazole on the oral, throat and colon microflora of man. Med Microbiol Immunol 1980; 168(1):1-10.

44. Loeshe WJ, Syed SA, Morison EC, et al. Metronidazole in periodontitis. I. Clinical and bacteriological results after 15 to 30 weeks. J Periodontol 1984; 55:325-55.

45. Lindhe J, Liljenberg B, Adielsson B. Effect of long-term tetracycline therapy on human periodontal disease J Clin Periodontol 1983;10: 590-601.

46. Lindhe J, Liljenberg B, Adielsson B, Borjesson J. Use of metronidazole as a probe in the study of human periodontal disease. J Clin Periodontol 1983; 10: 100- 112.

47. Lundstrom A, Johanson LA, Hamp SE. Effect of combined systemic antimicrobial therapy and mechanical plaque control in patients with recurrent periodontal disease J Clin Periodontol 1984; 11:321-30.

48. Jenkins WMM, MacFarlane TW, Gilmour WH, et al. Systemic metronidazole in the treatment of periodontitis. J Clin Periodontol 1989; 16:443-50.

49. Matarazzo F, Figueiredo LC, Cruz SEB, et al. Clinical and microbiological benefits of systemic metronidazole and amoxicillin in the treatment of smokers with chronic periodontitis: a randomized placebo-controlled study. J Clin Periodontol 2008; 35(10): 885-96.

50. Van Winkelhoff AJ, Rodenburg JP, Goene RJ, et al. Metronidazole plus amoxycillin in the treatment of Actinobacillus actinomycetemcomitans associated periodontitis. J Clin Periodontol 1989; 16:128-31.

51. Guerrero A, Griffiths GS, Nibali L, et al. Adjunctive benefits of systemic amoxicillin and metronidazole in non-surgical treatment of generalized aggressive periodontitis: a randomized placebo-controlled clinical trial. J Clin Periodontol 2005; 32(10):1096-107.

52. Sapadin AN, Fleischmajer R. Tetracsycline’s: nonantibiotic properties and their clinical implications. J Am Acad Dermatol 2006; 54(2):258–65.

53. Polson AM, Garrett S, Stoller N, et al. Multicenter study of doxycycline in treatment of periodontitis (abstract). J Dent Res 1995; 74(Spec Iss):26.

54. Okuda K, Wolff L, Oliver R, et al. Minocycline slow release formulation effect on subgingival bacteria. J Periodontol 1992; 63:73-9.

55. Goodson JM, Holborow D, Dunn RL, et al. monolithic tetracycline-containing fibres for controlled delivery to periodontal pockets. J Periodontol 1983; 54:575-9.

56. Heijl L, Dahlen G, Sundin Y, et al. A 4-quadrant comparative study of periodontal treatment using tetracycline-containing drug delivery fibers and scaling. J Clin Periodontol 1991; 18:111-6.

57. Pascale D, Gordon J, Lamster I, et al. Concentration of doxycycline in human crevicular fluid. J Clin Periodontol 1986; 13:841-4.

58. Sakellari D, Goodson JM, Kolokotronis A, et al. Concentration of 3 tetracycline’s in plasma, gingival crevice fluid and saliva. J Clin Periodontol 2000; 27(1):53-60.

59. Slots J, Rosling BG. Suppression of the periodontopathogenic microflora in localised juvenile periodontitis by systemic tetracycline. J Clin Periodontol 1983; 10:465-86.

60. Christersson LA, Slots J, Rosling BG, et al. Microbiological and clinical effects of surgical treatment of localised juvenile periodontitis. J Clin Periodontol 1985; 12:465-76.

61. Teles RP, Haffajee AD, Socransky SS. Microbiological goals of periodontal therapy. Periodontol 2000 2006; 42(1): 180-218.

62. Novak MJ, Polson AM, Adair SM. Tetracycline therapy in patients with early juvenile periodontitis. J Periodontol 1988; 59:366-72.

63. Xajigeorgiou C, Sakellari D, Slini T, et al. Clinical and microbiological effects of different antimicrobials on generalized aggressive periodontitis. Jl Clin Periodontol 2006; 33(4): 254-64.

64. Golub LM, Goodson JM, Lee HM, et al. Further evidence that tetracycline’s inhibit collagenase activity in human crevicular fluid and from other mammalian sourcesa. J Perio Res 1985; 20:12-23.

65. Golub LM, McNamara TF, D’Angelo G, et al. A nonantibacterial, chemically-modified tetracycline inhibits mammalian cillagenase activity. J Dent Res 1987; 66:1310-14.

66. Walker C, Gordon J. The effect of clindamycin on the microbiota associated with refractory periodontitis. J Periodontol 1990; 61(11):692-8.

67. Ohta Y. microbiological study on the periodontal lesions in advanced periodontitis. Changes in the regional flora and clinical features caused by short-term treatment with clindamycin. Skikwa Gakuho 1984; 8:1209-23.

68. Luthiger U. Clindamycin and penicillin V in the treatment of periodontal infections. A randomised study. Swiss Dent 1983; 4:41-3.

69. Roberts MC. Antibiotic toxicity, interactions and resistance development. Periodontol 2000 2002; 28:280-97.

70. Slots J, Feik D, Rams TE. In vitro antimicrobial sensitivity of enteric rods and pseudomonads from advanced adult periodontitis. Oral Microbiol Immunol 1990; 5(5):298-301.

71. Hoge HW, Kirkham DB. Periodontosis: treatment results in a 15-year old girl. JADA 1980; 101:795-7.

72. Kunihira DM, Caine FA, Palcains KG, et al. A clinical trial of phenoxymethyl penicillin for adjunctive treatment of juvenile periodontitis. J Periodontol 1985;56: 352-358.

73. Williams RC, Jeffcoat MK, Howell TH, et al. Altering the progression of human alveolar bone loss with the non-steroidal anti-inflammatory drug flurbiprofen. J Periodontol 1989; 60:485-90.

74. Howell TH, Fiorellini J, Weber HP, et al. Effect of the NSAID piroxicam, topically administered, on the development of gingivitis in beagle dogs. J Perio Res 1991; 26(3 Pt 1):180-3.

75. Golub LM, McNamara TF, Ryan ME, et al. Adjunctive treatment with subantimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis. J Clin Periodontol 2001; 28(2):146-56.

76. Caton JG, Ciancio SG, Blieden TM, et al. Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. J Periodontol 2000; 71(4):521-32.

77. http://www.kloxtechnologies.com/assets/healthy_periodontitis.png

78. http://files.dvm360.com/alfresco_images/DVM360/2013/11/12/c1faffef-8edb-48b9-9376-8087312c0404/table1.jpg.

Received on 07.01.2015 Modified on 13.02.2015

Res. J. Pharm. Dosage Form. & Tech. 7(1): Jan.-Mar. 2015; Page 82-89

DOI: 10.5958/0975-4377.2015.00012.9

Sr.no.	Stage of disease	Clinical signs	Treatment
1.	Stage 1: Gingivitis	Inflammation without periodontal support loss	Supragingival scaling, irrigation and polishing
2.	Stage 2: Early periodontitis	Inflammation, swelling, gingival bleeding upon probing, with up to 25 percent periodontal support loss	Supragingival and subgingival scaling, irrigation and polishing, followed by administration of local antimicrobial into the cleaned pocket
3.	Stage 3: Established periodontitis	Inflammation, edema, gingival bleeding upon probing, pustular discharge (suppuration), moderate bone loss, between 25 and 50 percent periodontal support loss	Supragingival and subgingival scaling, irrigation and polishing; extraction of affected teeth if owner cannot provide home care; if owner can provide long-term daily after-care, elimination or reduction of the pocket by gingivectomy (preserving at least 2mm attached gingiva) or apical reposition flap
s4.	Stage 4: Advanced periodontitis	Inflammation, edema, gingival bleeding upon probing, pustular discharge (suppuration), tooth mobility, marked (more than 50 percent) periodontal support loss	Extraction of affected teeth