AMAS in DENTISTRY.pptx.pptx antimicrobial agents in dentistry

dr aarti talwar

1. ANTIBIOTICS PRESENTED BY: DR.DR.AARTI TALWAR

2. CONTENTS INTRODUCTION HISTORY PIONEERS OF ANTIMICROBIAL THERAPY TERMINOLOGIES IDEAL CHARACTERISTICS CLASSIFICATION SELECTION OF ANTIBIOTICS ADVERSE EFFECTS RESISTANCE TO ANTIBIOTICS COMBINATION THERAPY CHEMOPROPHYLAXIS ANTIBIOTIC PROPHYLATIC REGIMEN FOR DENTAL PROCEDURES ANTIBIOTICS IN DENTISTRY SYSTEMIC ANTIBIOTICS LOCAL DRUG DELIVERY AGENTS CONCLUSION REFERENCES

3. INTRODUCTION Antibiotics are a naturally occurring, semisynthetic or synthetic type of antimicrobial agent that destroys or inhibits the growth of selective microorganisms, generally at low concentrations. -can kill or stop the multiplication of bacterial cells, -at concentrations that are relatively harmless to host tissues, -and therefore can be used to treat infections caused by bacteria. 3

4. ANTIBIOTIC ("opposing life“) Greek roots anti bios "against" "life” refer to any substance used against microbes. The term 'antibiosis' , meaning "against life", was introduced by the French bacteriologist Jean Paul Vuillemin as a descriptive name of the phenomenon exhibited by antibacterial drugs. The word "chemotherapy" was coined by Ehrlich. Ehrlich has been called the father of chemotherapy and the development of synthetic antimicrobial agents. 4

5. HISTORY The history of antimicrobial chemotherapy goes back in time long before the understanding and the recognition of the agents that are responsible for such infection. Mercury, for example, has been used in the treatment of syphilis since the 16th century . The use of quinine as an antimalarial agent can also be traced back as long ago as the 17th century. 5

6. PIONEERS IN ANTIMICROBIAL CHEMOTHERAPY 6

7. 7

8. By the 1960s, improvements in fermentation techniques and advances in medicinal chemistry permitted the synthesis of many new chemotherapeutic agents 8

9. TERMINOLOGIES

10. DRUG : any substance or product that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient. WHO (1966) ANTIBIOTICS - Substance produced by microorganisms that have the capacity to kill or inhibit the growth of other microorganisms at very low concentration. ANTIMICROBIAL THERAPY- Synthetic as well as naturally obtained drugs that act against microorganisms either systemically or at specific sites. 10

11. ANTISEPTIC - antimicrobial  substance or compound that is applied to living  tissue / skin  to reduce the possibility of  infection ,  sepsis , or  putrefaction . Antiseptics are generally distinguished from  antibiotics  by the latter's ability to safely destroy  bacteria  within the body, and from  disinfectants , which destroy microorganisms found on non-living objects. CHEMOTHERAPY -treatment of infectious diseases or malignancy with drugs to destroy microorganisms or cancer cells preferentially with minimal damage to host tissues.The infection maybe due to bacteria,fungi ,virus etc. MINIMUM INHIBITORY CONCENTRATION- minimum concentration of an antibiotic that prevents visible growth of a microorganism. 11

12. 1. Selectively toxic to the microbe but nontoxic to host cell. 2. Microbicidal rather than microbiostatic . 3. Relatively soluble , function even when highly diluted in body fluid. 4. Remain potent long enough to act and is not broken down or excreted prematurily . 5. Do not lead to the development of antimicrobial resistance. 6. Do not disrupt the host health by causing allergies or predisposing the host to other infection. 7. Reasonably priced. IDEAL CHARACTERISITICS 12

13. CLASSIFICATION MECHANISM OF ACTION TYPE OF ACTION SOURCE SPECTRUM OF ACTIVITY TYPE OF ORGANISM

14. MECHANISM OF ACTION INHIBIT CELL WALL SYNTHESIS= penicillins,cephalosporins,vancomycin AFFECT CELL MEMBRANE FUNCTION= amphotericin B,nystatin INHIBIT PROTEIN SYNTHESIS= chloramphenicol,tetracyclines,erythromycin ALTER PROTEIN SYNTHESIS= aminoglycosides INHIBIT DNA SYNTHESIS = acyclovir,zidovudine AFFECT DNA FUNCTION = rifampicin,metronidazole INHIBIT DNA GYRASE = fluoroquinolones ANTIMETABOLITES = sulphonamides,dapsone . 14

15. TYPE OF ACTION BACTERICIDAL AGENTS : penicillins,cephalosporins,aminoglycosides,fluoroquinolones,rifampicin, metronidazole BACTERIOSTATIC AGENTS: tetracyclines,chloramphenicol,sulphonamides,dapsone,erythromycin, clindamycin SPECTRUM OF ACTIVITY NARROW SPECTRUM Penicillin G Aminoglycosides BROAD SPECTRUM Tetracycline Chloramphenicol 15

16. SOURCE OF ANTIBIOTICS Fungi - Penicillin, Griseofulvin , Cephalosporin Bacteria - Polymyxin B, Bacitracin Actinomycetes -Aminoglycosides, Macrolides,Tetracyclines 16

17. TYPE OF ORGANISM AGAINST WHICH IT IS ACTIVE Antibacterial - Penicillin , Aminoglycosides, Erythromycin Antifungal - Amphotericin B, Ketoconazole, Antiviral - Zidovudine , Acyclovir Antiprotozoal - Chloroquine , Metronidazole Antihelminthic - Mebendazole , Pyrantel 17

18. SELECTION OF AN APPROPRIATE ANTIMICROBIAL AGENT 18

19. PATIENT FACTORS 1. Age : May affect kinetics of many Antimicrobial agents. Use of chloramphenicol in premature infants may produce gray-baby syndrome because the metabolic functions of the liver and renal excretion are not fully developed. Renal function declines with age; hence, elderly patients are more prone to ototoxicity and nephrotoxicity with aminoglycosides due to its reduced clearance by the kidney. 2. History of allergy : In patients with history of asthma, allergic rhinitis, hay fever, etc. there is an increased risk of penicillin allergy; hence such drugs should be avoided. 19

20. 3.Genetic abnormalities : Primaquine , pyrimethamine , sulphonamides , sulfones , fluoroquinolones , etc. may cause haemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. 4. Pregnancy : Most of the AMAs cross the placental barrier and may affect the developing foetus . The risk of teratogenicity is highest during the first trimester. For example, use of tetracyclines during pregnancy may affect foetal dentition and bone growth. There is an increased incidence of hepatotoxicity with tetracycline in pregnant women. Penicillin, erythromycin, cephalosporins are considered safer. 20

21. 5.Host defences : In immunocompromised patients (AIDS, leukaemias and other malignancies), normal defence mechanisms are impaired—bacteriostatic drugs may not be adequate; hence bactericidal agents should be used to treat infection. 6.Hepatic dysfunction : In patients with hepatic dysfunction, drugs like chloramphenicol, erythromycin, rifampin, etc. should be avoided or require dose reduction to avoid toxic effects. 7.Renal dysfunction: In renal failure, drugs that are eliminated via kidney can accumulate in the body and cause severe toxic effects. Hence aminoglycosides, vancomycin , amphotericin B, fluoroquinolones etc. should be avoided or require dose reduction in patients with impaired renal function. 21

22. 8. Local factors : Antimicrobial activity of sulphonamides is markedly reduced in the presence of pus. The activity of aminoglycosides is enhanced at alkaline pH, Presence of necrotic material and foreign body makes eradication of infection practically impossible. Hematomas foster bacterial growth. eg : Tetracycline, Penicillin and cephalosporin get bound to degraded Hb in the hematomas. Penetration barrier may hamper the access of the Antimicrobial agents to the site of infection in sub acute bacterial endocarditis. 22

23. DRUG FACTORS 1. Route of administration : Depending upon the severity and site of infection, the AMAs have to be chosen. Some of the AMAs can be administered orally as well as parenterally . For mild-to-moderate infections, oral route is usually preferred, but for severe infections like endocarditis, meningitis, etc. parenteral antibiotics are preferred during initial stages of therapy. 2.The spectrum of antimicrobial activity : For definite therapy, narrow spectrum drugs is preferred.For empirical therapy, broad spectrum drug is preferred. 3. Bactericidal/bacteriostatic effect : Bactericidal drugs kill the organisms while static drugs inhibit growth and multiplication. In immunocompromised states, the host- defence mechanisms are impaired; hence bactericidal drugs are required. 23

24. 4. Ability to cross blood–brain barrier (BBB): Pharmacokinetic profile of the drug is important, e.g. clindamycin is effective against anaerobes, but not useful for anaerobic brain abscess as it does not reach cerebrospinal fluid (CSF) and brain. Anaerobic brain abscess can be treated effectively with third-generation cephalosporins or combination of metronidazole and chloramphenicol. 5. Cost of the antimicrobial agent : The cost of treatment has to be considered while selecting an antimicrobial agent. The expensive antimicrobials should not be used routinely when alternative cheaper and effective AMAs are available. 24

25. ORGANISM RELATED CONSIDERATIONS Clinical diagnosis itself directs choice of the Antimicrobial agents. A good guess can be made, from the clinical features and the local experience about the type of organism and its sensitivity. Choice to be based on bacteriological examination, if no guess can be made about the infecting organism and its sensitivity, AMA should be selected on the basis of Culture and sensitivity testing. 25

26. ADVERSE EFFECTS OF ANTIMICROBIAL AGENTS 26

27. TOXICITY Local Irritancy: Experienced at the site of administration. Local irritation, pain and abscess formation at the site of i.m injection, thrombophlebitis of the injected vein are the complications. eg : Erythromycin, Tetracyclines , Systemic Toxicity: All AMAs produce dose related and predictable organ toxicities. eg : Aminoglycosides, Amphotericin B, Tetracycline 27

28. HYPERSENSITIVITY REACTIONS All AMAs are capable of causing hypersensitivity reactions which are unpredictable and unrelated to dose. They may range from rashes to anaphylactic shock eg : Penicillin, Cephalosporin, Sulfonamides 28

29. DRUG RESISTANCE It refers to unresponsiveness of a microorganism to an AMA. Resistance maybe acquired through mutation or gene transfer. 29

30. GENE TRANSFER (Infectious Resistance) : The resistance causing gene is passed from one organism to the other. Rapid spread of resistance can occur by this mechanism. The transfer of genes for drug resistance occurs by the following mechanisms: Transduction Transformation Conjugation 30

31. Conjugation : Conjugation is the transfer of genetic material carrying resistance between bacteria by direct contact through sex pilus , e.g. Escherichia coli resistance to streptomycin. 31

32. Transduction There is transfer of DNA carrying a gene for resistance from one bacterium to another through bacteriophage, e.g. resistance of strains of Staphylococcus aureus to antibiotics is mediated via transduction. 32

33. Transformation The resistance carrying genetic material that is released into the environment by resistant bacteria is taken up by other sensitive bacteria, e.g. penicillin G resistance in pneumococci. 33

34. MUTATION : It is a stable and heritable genetic change that occurs spontaneously and randomly among microorganisms. Antibiotic resistance occurs when an infection responds poorly to an antibiotic that once could treat it successfully. It’s the bacteria that have become resistant to the antibiotic, not the patient a change in their DNA - that gives them a new protein as a tool to fight the antibiotic. 34

35. There are many mechanisms by which this tool may work 35 prevent the antibiotic from entering the bacterial cell; pump the antibiotic out of the cell; destroy the antibiotic by enzymatic reaction; modify the antibiotic’s target so it no longer binds to the drug;

36. Cross-resistance Organisms that develop resistance to an antimicrobial agent may also show resistance to other chemically related AMAs. The cross-resistance among AMAs could either be one-way or two-way. Cross-resistance among tetracyclines and sulphonamides is usually ‘two-way’. The ‘one-way’ resistance is seen between neomycin and streptomycin. Neomycin-resistant organisms are resistant to streptomycin but streptomycin-resistant organisms may be sensitive to neomycin. 36

37. Prevention of development of resistance to antimicrobial agents It is done by: 1. Selecting right antimicrobial agent. 2. Giving right dose of the AMA for proper duration. 3. Proper combination of AMAs, e.g. in tuberculosis (TB), multidrug therapy (MDT) is used to prevent development of resistance to antitubercular drugs by mycobacteria. 4.Rapidly acting and narrow spectrum AMAs should be preferred whenever possible. 5.Combinations of AMAs should be used whenever prolonged therapy is undertaken. 6.Infection by organisms notorious for developing resistance must be treated intensively. 37

38. Superinfection ( Suprainfection ) It is defined as the appearance of a new infection due to antimicrobial therapy. The causative organism of superinfection should be different from that of the primary disease. Use of most AMAs causes some alterations in the normal microbial flora of the body. The normal flora contributes to host defence by elaborating substances, which inhibit pathogenic organisms. 38

39. Also the pathogen has to compete with the normal flora for nutrients to establish itself. Lack of competition may allow even a normally nonpathogenic component of the flora to predominate and invade. Suprainfection are more common when host defence is compromised, as in: Corticosteroid therapy Leukemias and other malignancies AIDS Agranulocytosis Diabetes 39

40. It can be minimized by ( i ) using specific antimicrobial agents, (ii) avoiding unnecessary use of AMAs and (iii) use of probiotics, e.g. Lactobacillus. 40

41. NUTRITIONAL DEFICIENCIES Prolonged use of AMAs alters the intestinal flora which synthesize some of the B complexes and Vitamin K – results in vitamin deficiencies. MASKING OF AN INFECTION A short course of an AMA may be sufficient to treat one infection but only briefly suppress another one contacted concurrently. The other infection will be masked initially, only to manifest later in a severe form. Eg : Syphilis masked by the use of single dose of penicillin which is sufficient to cure gonorrhoea 41

42. COMBINATION OF ANTIMICROBIAL AGENTS It is the simultaneous use of two or more antimicrobial agents for the treatment of certain infectious diseases. Indications/advantages of antimicrobial combinations 1. To broaden the spectrum of activity in mixed bacterial infections: Odontogenic infections, brain abscess, etc. are often due to both aerobic and anaerobic organisms. Hence, they require antimicrobial combination therapy. Metronidazole + ampicillin for ulcerative gingivitis. 2. In severe infections when the aetiology is not known : Combination of antimicrobial agents is used for empirical therapy. Later, the AMA should be selected according to the type of organism, culture and sensitivity results. 42

43. 3. To increase antibacterial activity in the treatment of specific infections (for synergistic effect ). Synergism may manifest in terms of decrease in MIC of one AMA in presence of another, or the MICs of both may be lowered. If MIC of both are lowered by 25 % or less, the pair is considered synergistic. 25-50% of each is considered additive. More than 50% indicate antagonism. A synergistic drug sensitizes the organisms to the action of the other member of the pair. This may manifest as a more rapid lethal action of the combination than either of the individual members. Ampicillin + gentamicin for enterococcal endocarditis. Carbenicillin + gentamicin for infections due to Pseudomonas. Penicillins , by inhibiting bacterial cell wall synthesis, facilitate the entry of gentamicin into the bacterial cell (synergistic effect). 43

44. 4. To prevent emergence of resistant microorganisms : In tuberculosis (TB), leprosy and HIV infection, combination therapy is used. 5. To reduce duration of therapy: Multidrug therapy is used in TB and leprosy. 6. To reduce adverse effects : Amphotericin B (AMB) and flucytosine in cryptococcal meningitis: the dose-dependent toxicity (especially nephrotoxicity) of AMB is reduced due to reduction in the dosage 44

45. DISADVANTAGES OF ANTIMICROBIAL DRUG COMBINATIONS 1. Increased toxicity, e.g. vancomycin with tobramycin may cause enhanced nephrotoxicity. 2. Increased cost. 3. Decreased antibacterial activity due to improper combinations, e.g. in pneumococcal meningitis, activity of penicillin G (bactericidal) against pneumococci will decrease if combined with tetracycline (bacteriostatic). 4. Increased likelihood of superinfection . 5. Irrational combination of AMAs can lead to development of resistance. 45

46. CHEMOPROPHYLAXIS Chemoprophylaxis is the administration of antimicrobial agents to prevent infection or to prevent development of disease in persons who are already infected . The ideal time to initiate therapy is before the organism enters the body or at least before the development of signs and symptoms of the disease. The difference between treating and preventing infection is that treatment is directed against a specific organism infecting an individual patient, while prophylaxis is often against all organism capable of causing infection. 46

47. 47 prevent endocarditis in patients with valvular lesion before undergoing any surgical procedures: Surgical procedures mucosal damage bacteraemia affects damaged valve endocarditis. protect healthy persons: Chloroquine / mefloquine is used for chemoprophylaxis of malaria for those travelling to malaria-endemic area. prevent infection in patients undergoing organ transplantation: Oral fluoroquinolones can be used. INDICATIONS

48. 48 prevent opportunistic infections in immunocompromised patients, e.g. cotrimoxazole is used to prevent Pneumocystis jiroveci pneumonia in AIDS patients. Prior to surgical procedures: in patients who are diabetics or on prolonged corticosteroids to prevent wound infection after surgery. prevent infection in patients with burns: Topical silver sulphadiazine and systemic antibiotics are used.

49. SUGGESTED CHEMOPROPHYLACTIC REGIMENS The effectiveness of chemoprophylaxis depends on the selection of specific antimicrobial agent, its dosage, time of initiation and duration of antimicrobial therapy. Empirical therapy : It is the use of antimicrobial agents before the identification of causative organism or availability of susceptibility test results, e.g. combination of amoxicillin, cefotaxime and vancomycin is used as empirical therapy for suspected bacterial meningitis (before test results are available) to cover possible organisms likely to cause meningitis. Definitive therapy : It involves the use of antimicrobial agent after identifi cation /susceptibility tests of causative organism responsible for the disease. 49

50. ANTIBIOTIC PROPHYLACTIC REGIMEN FOR DENTAL PROCEDURES 50

51. SYSTEMIC ADMINISTRATION OF ANTIBIOTICS IN PERIODONTAL THERAPY Systemic antibiotics are considered to enter the periodontal tissue and the periodontal pocket through transudation from the blood stream. The antibiotics within the periodontal connective tissue then cross the crevicular and junctional epithelia into the crevicular region around the tooth, into the GCF, associated with the subgingival plaque 51

52. They are administered : Patients who do not respond to conventional mechanical therapy. Acute periodontal infections associated with systemic manifestations. Prophylaxis in medically compromised patients. Adjunct to surgical and non surgical periodontal therapy. 52

53. The antimicrobial concentration in the GCF will be inadequate without the mechanical disruption of the microbial biofilm adherent to the tooth, i.e , subgingival plaque and calculus. The systemic antibiotic therapy may also suppress the periodontal pathogens in other parts of the mouth including tongue and the mucosal surfaces. This additional effect is considered beneficial because it may delay subgingival recolonization of pathogens. 53

54. DISADVANTAGES Inability to achieve high GCF concentrations Adverse drug reactions Resistant microorganisms Uncertain patient compliance 54

55. ANTIBIOTICS IN PERIODONTICS The principle antibiotic groups have been extensively evaluated for treatment of the periodontal diseases Tetracycline Minocycline Doxycycline Erythromycin Clindamycin Ampicillin Amoxicillin Metronidazole 55

56. TETRACYCLINE Group of broad-spectrum  antibiotic  compounds The first members of the tetracycline group to be described were chlortetracycline and oxytetracycline . Chlortetracycline was first discovered as an ordinary item in 1945  by  Benjamin Minge Duggar . Duggar derived the substance from a Missouri soil sample, golden- colored , fungus-like, soil-dwelling bacterium named  Streptomyces aureofaciens . Oxytetracycline  ( terramycin ) was isolated in 1949 by Alexander Finlay from a soil sample collected on the grounds of a factory in Terre Haute, Indiana. The  Pfizer  group, led by Francis A. Hochstein, determined the structure of  oxytetracycline , enabling Lloyd H. Conover to successfully produce  tetracycline  itself as a synthetic product in 1955. 56

57. Tetracycline molecules comprise a linear fused tetracyclic nucleus (rings designated A, B, C and D) to which a variety of  functional groups  are attached.  Tetracyclines are named for their four ("tetra-") hydrocarbon rings ("- cycl -") derivation ("- ine "). While all tetracyclines have a common structure, they differ from each other by the presence of  chloride ,  methyl , and  hydroxyl  groups. These  modifications  do not change their broad antibacterial activity, but do affect  pharmacological  properties such as  half-life  and binding to  proteins  in  serum . 57

58. Removal of the dimethylamine group at C4 reduces antibacterial activity.Replacement of the carboxylamine group at C2 results in reduced antibacterial activity but it is possible to add substituents to the amide nitrogen to get more soluble analogs like the prodrug   lymecycline . The simplest tetracycline with measurable antibacterial activity is 6-deoxy-6-demethyltetracycline. growth inhibitors ( bacteriostatic ) rather than killers of the infectious agent ( bacteriocidal ) and are only effective against multiplying microorganisms. Concentration in the gingival crevice is 2-10 times than in serum 58

59. CLASSIFICATION : 59

60. Pharmacokinetics When ingested, it is usually recommended that the more  water-soluble , short-acting tetracyclines (plain tetracycline, chlortetracycline,  oxytetracycline ,  demeclocycline  and  methacycline ) be taken with a full glass of water, either two hours after eating or two hours before eating. This is partly because most tetracyclines have chelating property and bind with food and also easily with  magnesium ,  aluminium ,  iron  and  calcium , which reduces their ability to be completely  absorbed  by the body. 60

61. Dairy products,  antacids  and preparations containing iron should be avoided near the time of taking the drug. Partial exceptions to these rules occur for  doxycycline  and  minocycline , which may be taken with food (though not iron, antacids, or calcium supplements).  Minocycline  can be taken with dairy products because it does not chelate calcium as readily, although dairy products do decrease absorption of minocycline slightly. Tetracyclines are widely distributed throughout the body, get concentrated in liver, spleen, bone, dentine, enamel of unerupted teeth but concentration in CSF is relatively low. They cross placental barrier, are metabolized in liver and excreted in urine. Doxycycline is excreted mainly in the faeces via bile. Therefore, doxycycline is safe for use in patients with renal insufficiency. Doxycycline undergoes enterohepatic cycling. 61

62. Mechanism of action Tetracycline antibiotics are  protein synthesis inhibitors .They inhibit translation process by binding to 30S subunit of bacterial ribosome and Prevent binding of aminoacyl tRNA to A site of ribosome. 62

63. 63 unwinding transcription codons

64. 64 A ( aminoacyl ) site, which accepts the incoming aminoacylated tRNA P ( peptidyl ) site, which holds the tRNA with the nascent peptide chain E (exit) site, which holds the deacylated tRNA before it leaves the ribosome. translation

65. 65 Tetracycline binds to 30s subunit

66. RESISTANCE : 3 mechanisms of resistance to tetracycline have been described : Decreased intracellular accumulation due to either impaired influx or increased efflux by an active transport protein pump. Ribosome protection due to production of proteins that interfere with tetracycline binding to the ribosome. Enzymatic inactivation of tetracyclines . 66

67. Adverse effects 1. Gastrointestinal: On oral administration, they can cause GI irritation manifested as nausea, vomiting, epigastric distress, abdominal discomfort and diarrhoea . 2. Phototoxicity : It is particularly seen with demeclocycline and doxycycline. They may also produce sunburn-like reaction in the skin on exposure to sunlight. They may also produce pigmentation of the nails. 67

68. 3. Effects on bones and teeth: Tetracyclines have calcium-chelating property, form tetracycline–calcium orthophosphate complex, which is deposited in growing bone and teeth. Use of tetracyclines in children and during pregnancy can cause permanent brownish discolouration of the deciduous teeth due to deposition of the chelate in the teeth. There is increased incidence of caries in such teeth. Tetracyclines also affect the linear growth of bones. The incidence of hepatotoxicity is more in pregnant women. Therefore, tetracyclines are contraindicated during pregnancy in the interest of both foetus and mother. It is also contraindicated in children up to the age of 8 years. 68

69. 4. Superinfection : It is common with older tetracyclines because of their incomplete absorption in the gut; they cause alteration of the gut flora. Superinfection occurs with organisms resistant to tetracyclines like Candida, Proteus, Pseudomonas, C. difficile , etc. 5. Hepatotoxicity: Acute hepatic necrosis with fatty changes is common in patients receiving high doses ( 2 g/day) intravenously. It is more likely to occur in pregnant women. 6. Renal toxicity: Demeclocycline may produce nephrogenic diabetes insipidus by inhibiting the action of antidiuretic hormone (ADH) on collecting duct. Fanconi syndrome: Use of outdated tetracyclines may damage the proximal renal tubules—the patient may present with nausea, vomiting, polyuria, proteinuria, acidosis, etc. 7. Hypersensitivity reactions: Skin rashes, fever, urticaria , exfoliative dermatitis, etc. may occur rarely. Cross-sensitivity among tetracyclines is common. 69

70. PRODUCT(S) CONTAINING TETRACYCLINE 70

71. TETRACYCLINE SYSTEMIC Achromycin 250 MG Capsule-Manufactured By Pfizer Ltd. treatment of bacterial infections acne , bacterial infection , bladder infection , bronchitis , brucellosis etc.. S ubstitutes:Alcyclin 250 MG Capsule, Hostacycline 250 MG Capsule Rancycline 250 MG Capsule, Tetracycllin 250 MG Capsule Brand names:  Sumycin ,  Tetracap ,  Tetracon 71

72. TETRACYCLINE TOPICAL Brand names:  Topicycline Tetracycline topical  is used in the treatment of: Acne , Bacterial Skin Infection MULTI-INGREDIENT MEDICATIONS CONTAINING TETRACYCLINE: bismuth subcitrate potassium/metronidazole/tetracycline systemic Brand names:  Pylera Drug class( es ):  H. pylori eradication agents diphenhydramine/hydrocortisone/ nystatin /tetracycline topical Brand names:  FIRST Mary's Mouthwash Drug class( es ):  mouth and throat products 72

73. USES IN DENTISTRY Used in the treatment of refractory periodontitis including Localised Aggressive Periodontitis. Ability to concentrate in the GCF and inhibit the growth of A. actinomycetemcomitans . They exert an anticollagenase effect that can inhibit tissue destruction. The combination therapy allows mechanical removal of root surface deposits and elimination of pathogenic bacteria from within the tissues. 73

74. Effective in treating periodontal diseases in part because their concentration in the gingival crevice is 2 to 10 times that in serum. This allows a high drug concentration to be delivered into periodontal pockets. In addition, several studies have demonstrated that tetracyclines at a low gingival crevicular fluid concentration (2 to 4  g/ml) are very effective against many periodontal pathogens. 74

75. DOXYCYCLINE Charlie Stephens' group at Pfizer created doxycycline--greatly improved stability and pharmacological efficacy. It was clinically developed in the early 1960s and approved by the FDA in 1967. Doxycycline, like other tetracycline antibiotics, is  bacteriostatic . It works by preventing bacteria from reproducing through the inhibition of protein synthesis. 75 HIGHLY LIPOPHILIC SO CAN EASILY ENTER CELLS DRUG IS EASILY ABSORBED AFTER ORAL ADMINISTRATION LARGE VOLUME OF DISTRIBUTION RE-ABSORBED IN THE RENAL TUBULES AND GIT LONG ELIMINATION HALF LIFE DOES NOT ACCUMULATE IN THE KIDNEYS OF PATIENTS WITH  KIDNEY FAILURE  DUE TO THE COMPENSATORY EXCRETION IN FAECES

76. Advantages of doxycycline 1. It can be administered orally as well as intravenously. 2. It is highly potent. 3. It is completely absorbed after oral administration. 4. Food does not interfere with its absorption. 5. It has a longer duration of action (t/2–24 h). 6. Incidence of diarrhoea is rare as it does not affect the intestinal flora. 7. It can be safely given to patients with renal failure, as it is excreted primarily in bile. 8.Doxycycline–metal ion complexes are unstable at acid pH, therefore more doxycycline enters the duodenum for absorption than the earlier tetracycline compounds. 76

77. PRODUCT(S) CONTAINING DOXYCYCLINE 77

78. DOXYCYCLINE SYSTEMIC Monodox (Oral) Generic name:   doxycycline  (oral route) Brand names:  Vibramycin ,  Monodox ,  Vibra -Tabs ,  Oracea , Acticlate CAP ® , Doryx ® used in the treatment of: Acne , Actinomycosis , Amebiasis , Anthrax , Bacterial Infection . Dosage Forms:Powder for Suspension, Capsule,Tablet , Syrup

79. For oral dosage forms (capsules, suspension, syrup, tablets):For infections: Adults—100 milligrams (mg) every 12 hours on the first day, then 100 mg once a day or 50 to 100 mg every 12 hours. Children 8 years of age or older weighing 45 kilograms (kg) or more—100 mg every 12 hours on the first day, then 100 mg once a day or 50 to 100 mg every 12 hours. Children 8 years of age or older weighing less than 45 kg—Dose is based on body weight and must be determined by your doctor. The dose is usually 4.4 mg per kg of body weight per day and divided into 2 doses on the first day of treatment. This is followed by 2.2 mg per kg of body weight per day, taken as a single dose or divided into two doses on the following days. 79

80. PERIOSTAT Generic Name:  doxycycline hyclate Brand Name:  Periostat Drug Class:  Tetracyclines  available as a 20 mg tablet formulation of doxycycline for oral administration. Doxycycline hyclate is a yellow to light-yellow crystalline powder which is soluble in water. Inert ingredients in the formulation are: hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, titanium dioxide, and triacetin . Each tablet contains 23 mg of doxycycline hyclate equivalent to 20 mg of doxycycline. 80

81. INDICATIONS Periostat ® (doxycycline hyclate ) is indicated for use as an adjunct to  scaling  and root planing to promote attachment level gain and to reduce pocket depth in patients with adult  periodontitis . DOSAGE Periostat ® 20 mg twice daily as an adjunct following scaling and root planing may be administered for up to 9 months. should be taken twice daily at 12 hour intervals, usually in the morning and evening. It is recommended that if Periostat ® (doxycycline hyclate ) is taken close to meal times, allow at least one hour prior to or two hours after meals. Safety beyond 12 months and efficacy beyond 9 months have not been established. 81

82. DOXYCYCLINE TOPICAL Brand names:  Atridox Drug class( es ):  mouth and throat products Doxycycline topical is used in the treatment of: Periodontitis MULTI-INGREDIENT MEDICATIONS CONTAINING DOXYCYCLINE: doxycycline/omega-3 polyunsaturated fatty acids systemic Brand names:  NutriDox Convenience Kit doxycycline/salicylic acid topical Brand names:  Avidoxy DK 82

83. MINOCYCLINE Minocycline , sold under the brand name  Minocin  among others, is a  tetracycline antibiotic  medication used to treat a number of bacterial infections such as  pneumonia . It is generally less preferred than the tetracycline  doxycycline . It is also used for the treatment of  acne  and  rheumatoid arthritis . Taking it together with food, including milk, has no relevant influence on resorption . It reaches highest  blood plasma  concentrations after one to two hours and has a  plasma protein  binding of 70–75%. The substance penetrates into almost all tissues; 83

84. Cynomycin 100 Capsule 84 MANUFACTURER = Pfizer Ltd SALT COMPOSITION= Minocycline (100mg) It is effective in some infections of the lungs, urinary tract, eyes, and others. It may also be used for the treatment of severe acne. SUBSTITUTES = Syno 100mg Capsule, Minopride 100mg Capsule, Minotag 100mg Capsule

85. BETA-LACTAM ANTIBIOTICS include penicillins , cephalosporins , carbapenems and monobactams . All of them have a -lactam ring in their chemical structure ,hence the name -lactam antibiotics. Most β-lactam antibiotics work by inhibiting  cell wall  biosynthesis in the bacterial organism and are the most widely used group of antibiotics The first β-lactam antibiotic discovered,  penicillin , was isolated from a strain of  Penicillium rubens  (named as  Penicillium notatum  at the time). Bacteria often develop resistance to β- lactam antibiotics by synthesizing a  β- lactamase , an enzyme that attacks the β- lactam ring. To overcome this resistance, β- lactam antibiotics can be given with  β- lactamase inhibitors  such as  clavulanic acid . 85

86. PENICILLIN Penicillins  are a group of  antibiotics  originally obtained from  Penicillium   moulds , principally  P. chrysogenum  and  P. rubens . Most penicillins in clinical use are chemically synthesised from naturally-produced penicillins . only two purified compounds are in clinical use:  penicillin G  ( intramuscular  or  intravenous use ) and  penicillin V  (given by mouth). Penicillins were among the first medications to be effective against many  bacterial infections  caused by  staphylococci  and  streptococci . 86

87. CLASSIFICATION 87

88. 88

89. MECHANISM OF ACTION: Interferes with the synthesis of bacterial cell wall. The action of penicillin requires the presence of a cell wall that contains peptidoglycans. 89

90. SYNTHESIS OF PEPTIDOGLYCAN 90 addition of 5 amino acids to N-acetyl muramic acid Most gram positive bacteria do not possess a periplasmic space but have only periplasm where metabolic digestion occurs and new cell peptidoglycan is attached.

91. 91 Next, N-acetyl glucosamine is added to the N-acetyl muramic acid to form a precursor of peptidoglycan. This peptidoglycan precursor is then transported across the cell membrane to a cell wall acceptor in the periplasm . Once in the periplasm , the peptidoglycan precursors bind to cell wall acceptors, and undergo extensive crosslinking.

92. 92 Two major enzymes are involved in crosslinking: transpeptidase and D- alanyl carboxypeptidase . These enzymes are also known as penicillin binding proteins because of their ability to bind penicillins and cephalosporins . several layers of peptidoglycan are formed all of which are crosslinked to create the cell wall. Gram positive bacteria have many more layers than gram negative bacteria and thus have a much thicker cell wall.

93. 93 Beta-lactam antibiotics include all penicillins and cephalosporins that contain a chemical structure called a beta-lactam ring. This structure is capable of binding to the enzymes that cross-link peptidoglycans. Beta-lactams interfere with cross-linking by binding to transpeptidase and D- alanyl carboxypeptidase enzymes, thus preventing bacterial cell wall synthesis.

94. PENICILLIN-G (BENZYL/CRYSTALLINE PENICILLIN) It is a narrow spectrum antibiotic , activity is limited to gram positive bacteria & few others. Penicillin G is acid liable- destroyed by gastric acid when given orally.Therefore,usually given by iv route. Absorption from i.m site is rapid and but painful. It is distributed mainly extracellularly ; reaches most body fluids but penetration in serous cavities and CSF is poor It is little metabolized because of rapid excretion t1/2 of penicillin in healthy adult is 30 min. Action can be prolonged by giving probenecid simultaneously. 94

95. Adverse effects Penicillin G is one of the most non toxic antibiotics. Local irritancy- Pain at i.m injection site, Nausea on oral injections, Thrombophlebitis of injected veins. Hypersensitivity: Rash, Itching, Urticaria , Fever, Wheezing, Anaphylaxis Superinfection : Rare because of its narrow spectrum 95

96. Jarisch – Herxheimer reaction: acute exacerbation of signs and symptoms of syphilis during penicillin therapy due to release of endotoxins from the dead organisms. Penicillin injected in a syphilitic patient may produce shivering, fever, myalgia, exacerbation of lesion and even vascular collapse. This is due to the sudden release of spirochetal lytic products and lasts 12-72 hours. Aspirin and sedation for relief of symptoms. 96

97. Therapeutic Uses: Dental infections : Periodontal abscess Periapical abscess Pericoronitis Necrotizing ulcerative gingivitis Oral cellulitis Streptococcal infections : Pharyngitis Otitis media Scarlet fever Pneumococcal infections : Pneumonia Meningococcal infections Meningitis Diphtheria, Tetanus Prophylactic use Rheumatic fever Gonorrhoea Infective endocarditis Surgical infections 97

98. SEMISYNTHETIC PENICILLINS Semisynthetic penicillins are produced by chemically combining specific side chains. This is to overcome the short comings of natural penicillin such as: Poor oral efficacy Susceptibility to penicillinase Narrow spectrum of activity Hypersensitivity 98

99. CLASSIFICATION: ACID RESISTANT PENICILLIN Phenoxymethyl penicillin (penicillin V) PENICILLINASE RESISTANT PENICILLIN: Methicillin Oxacillin Cloxacillin EXTENDED SPECTRUM PENICILLINS Aminopenicillins : Ampicillin, Amoxicillin Carboxypenicillins : Ticarcillin Ureidopenicillins : Mezlocillin , Piperacillin Mecillinam ( Amdinocillin ) β LACTAMASE INHIBITORS: Clavulanic acid and sulbactam 99

100. AMPICILLIN VS AMOXICILLIN 100

101. AMPICILLIN Ampicillin can be administered by  mouth , an  intramuscular injection  (shot) or by  intravenous infusion .   Ampilin 250 MG Tablet Manufactured By :Hetero Healthcare Ltd Substitutes : Synthocillin 500mg Capsule,Neocillin 500mg Capsule,Ampurin 500mg Capsule,Mahacillin 500mg Capsule Uses : UTI , RTI, Meningits , Gonorrhoea Interactions : Hydrocotisone inactivates ampicillin mixed in IV 101

102. AMOXICILLIN Amoxicillin ( α- amino-p- hydroxybenzyl penicillin) is a semisynthetic derivative of penicillin with a structure similar to ampicillin but with better absorption when taken by mouth, thus yielding higher concentrations in blood and in urine.Amoxicillin diffuses easily into tissues and body fluids.  Novamox 500 Capsule MANUFACTURER: Cipla Ltd SALT COMPOSITION: Amoxycillin (500mg) SUBSTITUTES : Moxilium 500mg Capsule, Radimox 500mg Caps Novamox 500 Capsule helps to eliminate a bacteria known as H. pylori in people with peptic ulcer disease. It is a broad-spectrum antibiotic that fights and stops the growth of many types of bacteria. This medicine is best taken with a meal to reduce the chance of a stomach upset. 102

103. BETA – LACTAMASE INHIBITORS Beta-lactamases are a family of enzymes produced by many gram positive and gram negative bacteria that inactivate the beta-lactam antibiotics by opening the beta-lactam ring. They structurally resemble -lactam molecules. Beta-lactamase inhibitors bind to lactamases and inactivate them. Coadministration of these drugs with -lactams increases the activity of -lactams by preventing them from enzymatic destruction. CLAVULANIC ACID, SULBACTAM AND TAZOBACTAM 103

104. CLAVULANIC ACID Obtained from Streptomyces clavuligerus . It inhibits a wide variety of beta-lactamases produced by both gram positive and gram negative bacteria. Also called ‘suicide inhibitor’ as it gets inactivated after binding to the enzyme. 104

105. Uses: Addition of clavulanic acid reestablishes the activity of amoxicillin against beta-lactamase producing bacteria. Coamoxiclav (Amoxicillin + clavulanic acid) is indicated for : Skin and soft tissue infections,Gonorrhoea Urinary, Biliary, Respiratory tract infections Dental infections caused by β – lactamase producing bacteria. Dose: Amoxicillin 250mg + clavulanic acid 125mg tab; TDS, severe infections 4 tabs 6 hourly. 105

106. Coamoxiclav (Amoxicillin + clavulanic acid) SUBSTITUTES :augmentin,moxclav,amonate USES :Skin and soft tissue infections,Urinary , Biliary, Respiratory tract infections ,Gonorrhoea, Dental infections caused by β – lactamase producing bacteria. Dose : Amoxicillin 250mg + clavulanic acid 125mg tab; TDS, severe infections 4 tabs 6 hourly. Amoxicillin/ clavulanic acid is the International Nonproprietary Name (INN) and co- amoxiclav is the British Approved Name (BAN). 106

107. CEPHALOSPORINS These are group of semisynthetic antibiotics derived from `Cephalosporin-C’ obtained from a fungus Cephalosporium . All cephalosporins are bactericidal and have the same mechanism of action as penicillin. Penicillins are superior to these in their range of action against periodontal pathogenic bacteria. Rashes, Urticaria , Fever and GI upset have been associated with cephalosporins . 107

108. 1 st GENERATION 2 nd GENERATION 3 rd GENERATION 4 th GENERATION 5 th GENERATION ORAL ORAL ORAL ORAL ORAL CEFADROXIL CEPHALEXIN CEFACLOR CEFUROXIME CEFIXIME …….. ………. PARENTERAL PARENTERAL PARENTERAL PARENTERAL PARENTERAL CEFAZOLIN CEPHALOTHIN CEFUROXIME CEFOXITIN CEFTRIAXONE CEFOPERAZNE CEFOTAXIME CEFEPIME CEFPIROME CEFTOBIPROLE CEFTAROLINE CEFTOLOZANE 108

109. Adverse effects : Local irritancy Diarrhoea Hypersensitivity reactions Nephrotoxicity Neutropenia (rare) Cefadrox 500mg Tablet MANUFACTURER: Aristo Pharmaceuticals Pvt Ltd SALT COMPOSITION: Cefadroxil (500mg) SUBSTITUTES: Adrocef , Aroxil, Codroxil 500mg Tablet 109

110. METRONIDAZOLE Nitroimidazole compound developed in France to treat protozoal infections Bactericidal to anaerobic microoganisms . Permeable through the bacterial cell wall, the drug binds DNA and disrupts the helical structure. Breakage of the DNA strands follows leading to cell death It enters the cell by diffusion, where its nitro group is converted into a highly reactive nitro radical which exerts cytotoxicity. 110

111. Plasma t1/2 is 8hrs Effective against A. actinomycetemcomitans when used in combination with other antibiotics Also effective against anaerobes such as Porphyromonas gingivalis and Prevotella intermedia . Metrogyl 400 Tablet MANUFACTURER= J B Chemicals and Pharmaceuticals Ltd SALT COMPOSITION= Metronidazole (400mg) SUBSTITUTES = Metropen 400mg,metrogyl 400mg tab 111

112. Adverse Effects: Most Common=Nausea, Metallic taste, Abdominal cramps Less Frequent=Headache, Glossitis , Dryness of mouth and dizziness Prolonged Administration=Peripheral Neuropathy and CNSa 112

113. Contraindications : Chronic alcoholics First trimester of pregnancy Neurological disease Blood dyscrasias Interactions: A Disulfiram -like intolerance to alcohol occurs in some patients. Avoided for patients on anticoagulant therapy 113

114. USES IN PERIODONTICS It has been used to treat Gingivitis, ANUG, Chronic periodontitis, and Aggressive periodontitis. Has been used in monotherapy as well as in combination with scaling and root planing and with other antibiotics. A single dose of metronidazole 250 mg orally appear both in serum and GCF in sufficient quantities to inhibit a wide range of suspected periodontal pathogens. 114

115. Administered systemically 750-1000 mg/day for 2 weeks, it reduces the growth of anaerobic flora, including spirochaetes , and decreases the histopathologic signs of periodontitis. Most common regimen is 250 mg t.i.d for 8 days. Metronidazole used as supplement to rigorous scaling and root planing resulted in the reduced need for surgery compared with root planing alone. It offers some benefit in the treatment of refractory periodontitis, particularly when used in combination with amoxicillin. 115

116. FLUOROQUINOLONES The first quinolone, nalidixic acid, is a urinary antiseptic. Fluoroquinolones are synthetic fl uorinated analogues of nalidixic acid. The important fluoroquinolones are norfl oxacin , ciprofl oxacin , pefloxacin , ofl oxacin , levofl oxacin , gemifl oxacin and moxifl oxacin . 116

117. 1 st GENERATION 2 nd GENERATION 3 rd GENERATION 4 th GENERATION NALIDIXIC ACID CINOXACIN CIPROFLOXACIN NORFLOXACIN OFLOXACIN GATIFLOXACI LEVOFLOXACIN MOXIFLOXACIN SITAFLOXACIN TROVAFLOXACIN 117

118. Pharmacokinetics : Rapidly absorbed orally, but food delays absorption and first pass metabolism occurs. The most prominent feature is High tissue penetrability, Concentration in lung, sputum, muscle, bone, prostrate and phagocytes exceeds that in plasma, but CSF and aqueous levels are lower. It is excreted primarily in urine, both by glomerular filtration and tubular secretion. 118

119. Urinary and Biliary concentrations are 10-50 fold that in plasma. t ½ 3 - 5 hrs Dose 250 - 750 mg b.i.d orally, 100 - 200 mg i.v Uses : Typhoid Bone & soft tissue infections Respiratory infections Urinary tract infections Tuberculosis Conjunctivitis 119

120. In Periodontics : It demonstrates minimal effect on streptococcus species, associated with periodontal health, it may facilitate the establishment of a microflora associated with periodontal health. At present ciprofloxacin is the only antibiotic in periodontal therapy to which all strains of aggregatibacter actinomycetemcomitans are susceptible. It has been used in combination with metronidazole. 120

121. Adverse effects : Gastrointestinal : Nausea, Vomiting, Bad Taste CNS: Dizziness, Headache, Restlessness, Anxiety, Insomnia, Impairment Of Concentration, Dexterity, Tremors And Seizures (rarely) Skin and Hypersensitivity: Rash, Pruritus, Photosensitivity, Urticaria , Swelling Of Lips etc Tendonitis and Tendon Rupture Cartilage damage in weight bearing joints in children 121

122. MACROLIDE ANTIBIOTICS ERYTHROMYCIN Erythromycin is the first member discovered in the 1950s It was isolated from Streptomyces erythreus . Later additions - Roxithromycin , Azithromycin, Clarithromycin Used as an alternative to penicillin. 122

123. MECHANISM OF ACTION : Bacteriostatic at low and cidal at high concentrations. They act by inhibiting protein synthesis. They bind to 50S ribosomes and interferes with translocation. They are active against mostly gram positive and a few gram negative bacteria. It is several fold more active in the alkaline medium, because the nonionized form of the drug is favoured at higher pH. 123

124. Pharmacokinetics : It is acid labile. To protect it from gastric acid, it is given as enteric coated tablets, from which absorption is incomplete and food delays absorption by retarding gastric emptying. It is widely distributed in the body, enters cells and into abscesses, crosses serous membrane and placenta, but not blood brain barrier. Excreted primarily in bile in the active form. Renal excretion minor, dose need not be altered in renal failure. 124

125. The plasma t ½ is 1.5 hrs , but it persists longer in tissues. Dose: 250 - 500 mg tab 6 hourly (max. 4 g / day) Children 30 - 60 mg/ kg/ day ERYTHROCIN, ERYSTER Uses : Drug of choice Atypical pneumonia Pharyngitis Tonsillitis Respiratory / ENT infections 125

126. In Periodontics : Periodontal / periapical abscesses Necrotizing ulcerative gingivitis Post extraction infections. Adverse effects : Epigastric pain Diarrhoea High doses - reversible hearing impairment Hypersensitivity 126

127. AZITHROMYCIN This macrolide drug has expanded spectrum, improved pharmacokinetics, better tolerability and drug interaction profiles. High activity against respiratory pathogens. Acid stable Rapid oral absorption Marked tissue distribution Intracellular penetration. AZITHRAL, AZIWOK 250, 500 mg cap 127

128. Major advantage : Convenient dosing : 500 mg od for 3 days or 500 mg initial loading dose followed by 250 mg od for 4 days Concentration in most tissues exceed that in plasma particularly higher concentrations are attained in macrophages and fibroblasts. Slow release from intracellular sites contributes to its long terminal t ½ > 50 hrs. Adverse effects: Mild gastric upset, Abdominal pain (less than erythromycin) Headache, Dizziness 128

129. CLINDAMYCIN A lincosamide antibiotic similar in mechanism of action and spectrum of activity to erythromycin, with which it exhibits partial cross resistance. Bacteriostatic drug. Effective against anaerobic bacteria. Used when patient allergic to penicillin. Oral absorption good. 129

130. Penetrates into most skeletal and soft tissues, but not to brain and CSF; accumulates in neutrophils and macrophages. Is largely metabolized and metabolites are excreted in urine and bile. t ½ is 3 hrs. DALCAP, DALCIN, CLINCIN – 150, 300 mg cap. QID Mechanism of action : Inhibits protein synthesis by binding to 50S ribosomal subunit and interferes with translocation. 130

131. Adverse effects : Rashes Urticaria Abdominal pain Major problems – Diarrhoea and Pseudomembranous enterocolitis (Metronidazole alternatively Vancomycin given to treat it ) 131

132. DRUG INTERACTIONS PENICILLINS : Efficacy decreased by tetracyclines , erythromycin and cephalosporins Potentiates anticoagulant effects of warfarin and aspirin ERYTHROMYCIN : Potentiates vasoconstrictive effects of ergot alkaloids Potentiates toxicity of theophylline TETRACYCLINES : Potentiates anticoagulant effects of warfarin Potentiates nephrotoxicity of diuretics Decreases bacteriocidal effects of penicillins and ciprofloxacin Digestive absorption inhibited by antacids, antianemics , magnesium-containing drugs and milk product 132

133. 4. METRONIDAZOLE : Potentiates anticoagulant effects of coumadin (warfarin) Alcohol consumption and disulfiram elicit “ antabuse reaction” (abdominal cramps, nausea, vomiting, headaches, toxic psychosis) Potentiated by chloramphenicol and cimetidine Potentiates phenytoin and phenobarbital 5. CIPROFLOXACIN : Potentiates toxicity of theophylline Digestive absorption inhibited by antacids Reduces metabolism of caffeine Enhances effect of warfarin 6. CEPHALEXIN : Potentiates anticoagulant effects of coumadin (warfarin) and aspirin Bacteriocidal effects decreased by tetracyclines and erythromycin 133

134. LOCAL DRUG DELIVERY 134

135. SUBGINGIVAL METRONIDAZOLE Elyzo 25% Dentalgel (EDG) which is developed for use in the treatment of periodontitis is a suspension of metronidazole benzoate (40%) in a mixture of glyceryl mono- oleate (GMO) and triglyceride (sesame oil). Metronidazole can be detected in the periodontal pockets 24-36 h after application.  It is applied in viscous consistency to the pocket, where it is liquidized by the body heat and then hardens again, forming crystals in contact with water. As a precursor, the preparation contains metronidazole benzoate, which is converted into the active substance by esterases in GCF. 135

136. TETRACYCLINE CONTAINING FIBRES (ACTISITE) Actisite ® (tetracycline periodontal) periodontal fiber for periodontal pocket placement consists of a 23 cm (9 inch) monofilament of ethylene/vinyl  acetate  copolymer, 0.5 mm in diameter, containing 12.7 mg of evenly dispersed tetracycline hydrochloride, USP.Actisite ® (tetracycline periodontal) fiber provides continuous release of tetracycline for 10 days. 136

137. SUBGINGIVAL MINOCYCLINE (ARESTIN) ARESTIN (minocycline hydrochloride) microspheres, 1mg is a subgingival sustained-release product containing the  antibiotic  minocycline hydrochloride incorporated into a bioresorbable polymer, Poly ( glycolide -co-dl- lactide ) or PGLA, for professional subgingival administration into  periodontal  pockets. Each unit-dose cartridge delivers minocycline hydrochloride equivalent to 1 mg of minocycline free base. 2% minocycline is encapsulated into bioresorbable microspheres in a gel carrier. 137

138. DOXYCYCLINE (ATRIDOX) The ATRIDOX ( doxycycline   hyclate ) ® product is a subgingival controlled-release product composed of a two syringe mixing system. Syringe A contains 450 mg of the ATRIGEL® Delivery System, which is a bioabsorbable , flowable polymeric formulation composed of 36.7% poly( DLlactide ) (PLA) dissolved in 63.3% N-methyl-2-pyrrolidone (NMP). Syringe B contains 50 mg of doxycycline hyclate which is equivalent to 42.5 mg doxycycline. The constituted product is a pale yellow to yellow viscous liquid with a concentration of 10% of doxycycline hyclate . Upon contact with the crevicular fluid, the liquid product solidifies and then allows for controlled release of drug for a period of 7 days. 138

139. SUBGINGIVAL MINOCYCLINE (ARESTIN) ARESTIN (minocycline hydrochloride) microspheres, 1mg is a subgingival sustained-release product containing the  antibiotic  minocycline hydrochloride incorporated into a bioresorbable polymer, Poly ( glycolide -co-dl- lactide ) or PGLA, for professional subgingival administration into  periodontal  pockets. Each unit-dose cartridge delivers minocycline hydrochloride equivalent to 1 mg of minocycline free base. 2% minocycline is encapsulated into bioresorbable microspheres in a gel carrier. 139

140. IRRIGATION WITH ANTIBIOTICS 10% TETRACYCLINE HCL As per Silverstein et al.8 when a waterpik is used to deliver tetracycline subgingivally , an increased levels of tetracycline is obtained within gingival crevicular fluid and these levels are more than that achieved with antibiotics administered systemically. Additionally, tetracycline has been shown to be efficacious against the periodontal diseasecausing pathogenic microorganisms, by increasing the attachment of fibroblasts to fibronectin -associated dental structures and by inhibiting the activity of collagenase. 140

141. COMMON ANTIBIOTIC THERAPIES IN THE TREATMENT OF PERIODONTAL DISEASES Amoxicillin - 500 mg / t.i.d / 5 days Metronidazole - 400 mg / t.i.d / 8 days Clindamycin - 300 mg / t.i.d / 10 days Doxycycline or minocycline - 100 - 200 mg/ o.d /21days Ciprofloxacin - 500 mg / b.i.d / 8 days Azithromycin - 500 mg / o.d / 4 - 7 days Combination Therapy : Metronidazole + Amoxicillin - 250 mg of each drug / t.i.d / 8 days Metronidazole + Ciprofloxacin - 500 mg of each drug / b.i.d / 8 days 141

142. NECROTISING ULCERATIVE GINGIVITIS Amoxicillin 500 mg every 6 hours for 10 days For amoxicillin sensitive patients Erythromycin -500 mg every 6 hours Metronidazole – 500 mg bid for 7 days 142

143. ACUTE PERICORONITIS Antibiotics are advised in severe cases and in patients who may have clinical evidence of diffuse microbial infiltration of the tissue Amoxcillin 500 mg + metronidazole 400mg tid for 5 days Ornidazole 500 mg + ofloxacilin 200 mg bid for 5 days 143

144. ACUTE HERPETIC GINGIVOSTOMATITIS Earlier consisted of palliative therapy Can give antiviral therapy (acyclovir ) 15 mg/kg of an acyclovir suspension given five times daily for 7 days. 144

145. ACUTE PERIODONTAL ABSCESS Amoxicillin: Loading dose of 1.0 g followed by a maintenance dose of 500 mg/ t.i.d . for 3 days revaluation Allergy to ß-lactam drugs Azithromycin: loading dose of 1.0 g on day 1, followed by 500 mg od for 3 days OR Clindamycin: loading dose of 600 mg on day 1, followed by 300 mg/ q.i.d . for 3 days 145

146. AGGRESSIVE PERIODONTITIS Systemic tetracycline -250 mg qid for atleast 1 week should be given in conjuction with mechanical debridement. Doxycycline -100 mg od may be used instead of tetracycline. 146

147. FAILURES OF ANTIBIOTIC THERAPY Inappropriate choice Antibiotic resistance microorganisms Low blood concentration Growth rate of microorganisms Impaired host defense Non compliance Antagonism Lack of penetration Decreased blood flow Local factors Source of infection 147

148. CONCLUSION Antibiotics are powerful medicines that  fight certain infections and can save lives when used properly . They are valuable and in some instances life-saving drugs. They can only retain this position in medicine and dentistry if used with care and prescribed appropriately. 148

149. REFERENCES : Essentials of medical pharmacology- K D Tripathi - 7th edition Carranza’s Clinical Periodontology - Newman, Takei, Klokkevold , Carranza- 10th edition Antibiotic/Antimicrobial use in Dental practice - Michael Newman, Kenneth Kornman Antibiotics in periodontal therapy advantages and disadvantages Slots and Rams J Clin Periodontol l990; 17: 479-493. Systemic & topical antimicrobial therapy in Periodontics Periodontology 2000; 1996, vol 10 Systemic antibiotics in the treatment of periodontal disease Periodontology 2000, Vol. 28, 2002, 106–176 149