Drugs used in endodontics


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Drugs used in endodontics

  1. 1. DRUGS USED IN ENDODONTICS By Dr.Anoop.V.Nair PG Dept of Cons. Dentistry & Endodontics KVG Dental College, Sullia
  2. 2. CONTENTS • Introduction and classifications • PART I Pain and analgesics • PART II Corticosteroids • PART III Antibiotics and its usage • PART IV Local anaesthetics • PART V Antimicrobial agents • PART VI Drugs and pregnant patients • PART VII Anxiety and fear • PART VIII The medically complex endodontic patient References
  3. 3. • A medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body -Oxford dictionary • A pharmaceutical drug, also referred to as a medicine or (loosely) medication, officially called medicinal product, can be loosely defined as any chemical substance — or product comprising such — intended for use in the medical diagnosis, cure, treatment, or prevention of disease. • The word pharmaceutical comes from the Greek word Pharmakeia. • According to the Food, Drug, and Cosmetic Act, (1) : a substance recognized in an official pharmacopoeia or formulary (2) : a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease (3) : a substance other than food intended to affect the structure or function of the body (4) : a substance intended for use as a component of a medicine but not a device or a component, part, or accessory of a device Definitions
  4. 4. CLASSIFICATIONS Based on when the drug is administered- • Pre treatment- analgesics, antibiotics, anti-anxiety • Treatment- corticosteroids, antibiotics, anti-microbials, local anaesthesia • Post treatment- antibiotics, corticosteroids, analgesics Based on route of administration- • Local- topical antibiotics, anti-microbials, topical anaesthetics • Systemic- oral- antibiotics, analgesics, anti anxiety - injectable- im/iv- antibiotics, analgesics, sedatives • Inhalation- sedatives, anaesthesia
  6. 6. • The skill of the clinician is often judged primarily by their success or failure of pain control. -Cohen, Pathways of the Pulp
  7. 7. The Trigeminal Pain System
  8. 8. ANALGESICS- NONNARCOTIC Management of endodontic pain is multifactorial and directed at reducing the peripheral and central components of hyperalgesia through combined endodontic procedures and pharmacotherapy. 2 classes mainly- NSAIDS Acetaminophen
  9. 9. NSAIDS • Very effective in managing pain of inflammatory origin- binds to plasma proteins- exhibit increased delivery to inflamed tissue via extravasation of plasma proteins. • Less studies done comparing NSAIDS on endodontic pain in particular • Ibuprofen- considered the prototype of contemporary NSAIDs and has a well-documented efficacy and safety profile. • Etodolac (i.e., Lodine) has minimal gastrointestinal (GI) irritation. • Ketoprofen (i.e., Orudis) has been shown in some studies to be somewhat more analgesic than ibuprofen
  10. 10. • They act primarily through the inhibition of cyclooxygenase (COX) enzymes 1 and2. • COX-1 is expressed throughout the body and has a role in protection of stomach mucosa, kidney function and platelet action. • COX-2 is induced by various endogenous compounds such as cytokines, mitogens and endotoxins in inflammatory cells and is responsible for the elevated production of prostaglandins during inflammation. • Nakanishi et al demonstrated high levels of expression of COX-2 in samples of human dental pulps with a diagnosis of irreversible pulpitis. • These two proteins share a 60% homology and catalyze the conversion of arachidonic acid into prostaglandin E2. • PGE2 is subsequently metabolized by a variety of syntheses into PGH2, PFI2, PGD2, PGF2 and thromboxane A2. • Inhibiting COX-2 blocks prostaglandin formation and ultimately prevents inflammation and sensitization of the peripheral nociceptors. Pharmacological Strategies to Control Post-operative Endodontic Pain Zahed Mohammad, Alireza Farhad, Meisam Khalesi Dent Res J 2007; 4(2): 61-68
  11. 11. • NSAIDS combined with other drugs (e.g., flurbiprofen with tramadol) or pretreatment and posttreatment application of NSAIDs provides effective pain control. • The introduction of selective inhibitors of COX-2 offered the potential for both analgesic and antiinflammatory benefits and reduced GI irritation. • Oral surgery pain studies evaluating COX-2 inhibitors have indicated that Rofecoxib (i.e.,Vioxx) has significant analgesic efficacy. • COX-2 levels are increased in inflamed human dental pulp, and a COX-2 inhibitor (rofecoxib) is analgesic in patients with endodontic pain. • Concern has been raised that the COX-2 inhibitors may also display at least some GI irritation in patients with preexisting GI disease
  12. 12. • Increased risk for prothrombic events following long-term administration of rofecoxib (VIOXX), which led to the withdrawal of this drug from the market in 2004. • Diclofenac (Voltaren) is a relatively COX-2-selective drug and seems to have a similar degree of COX-2 selectivity as celecoxib. • Diclofenac was associated with increased CV events. • In the randomized trial analysis, there was an increase in CV risk with high-dose ibuprofen.
  13. 13. Based on the available data, the FDA has requested that manufacturers of all prescription products containing nonselective NSAIDs revise their product labeling to include (1) a boxed warning regarding the potential serious adverse CV events and the serious, potentially life-threatening GI adverse events associated with the use of this class of drugs (2) a contraindication for use in patients who have recently undergone coronary artery bypass surgery (3) a medication guide for patients, regarding the potential for CV and GI adverse events associated with the use of this class of drugs. Given this situation and reasonable alternative NSAIDs, its recommended not considering COX-2 inhibitors for treating routine endodontic pain patients.
  14. 14. Limitations and Drug Interactions • NSAIDs exhibit an analgesic ceiling that limits the maximal level of analgesia and induces side effects, including those affecting the GI system (3% to 11% incidence) and the CNS (1% to 9% incidenc of dizziness and headache). • NSAIDs are contraindicated in patients with ulcers and aspirin hypersensitivity. • Also associated with severe GI complications • Risk of adverse effects increases with increasing lifetime accumulated dose of these drugs. • Acetaminophen and opioid combination drugs represent alternatives for those patients unable to take NSAIDs
  15. 15. Acetaminophen • one of the most commonly used drugs • found in Combination products for the relief of pain and symptoms of cold or flu. • considered safe when taken at normal doses, but in higher doses causes liver toxicity and has become the most common cause of acute liver failure • conjugated in the liver to form inactive metabolites.
  16. 16. • A small portion is metabolized by the cytochrome P450 system to form N- acetyl-p-benzoquinone imine (NAPQI), which is very toxic but is generally detoxified by glutathione and converted into nontoxic compounds. • Large doses of acetaminophen saturate the main route of metabolism, causing more acetaminophen to be converted to NAPQI. • Liver injury occurs once glutathione becomes depleted and NAPQI is allowed to accumulate. • Healthy adults should not take more than 4 g (4000 mg) of acetaminophen in a 24-hour period.
  17. 17. Opioid Analgesics • potent analgesics • used in dentistry in combination with acetaminophen, aspirin, or ibuprofen • activate mu opioid receptors located at several important sites in the brain • Activation of these receptors inhibits the transmission of nociceptive signals from the trigeminal nucleus to higher brain regions • opioids also activate peripheral opioid receptors located in dental pulp • Intraligamentary injection of morphine has been shown to significantly reduce pain in endodontic patients and other inflammatory pain states • Adverse side effects, which can include nausea, emesis, dizziness, drowsiness, and the potential for respiratory depression and constipation.
  18. 18. A combination formulation is preferred because it permits a lower dose of the opioid, thereby reducing side effects
  19. 19. • Codeine is often considered the prototype opioid for orally available combination drugs. • 60-mg dose of codeine produces less analgesia than either aspirin 650 mg or acetaminophen 600 mg
  21. 21. • Corticosteroids contain 21 carbon atoms in a four membered hydrocarbon ring system. • They comprise glucocorticoids and mineral corticoids. • Glucocorticoids have been used in endodontics for their potent anti- inflammatory effects. • The anti-inflammatory properties of glucocorticoids were first appreciated and utilized as an adjunct in endodontic therapy almost half a century ago. • Glucocorticoids have been used as an intracanal medication either alone or in combination with antibiotics/ antihistamines, and systemically as a means to decrease pain and inflammation in endodontic patients
  22. 22. • Glucocorticoids have effects on carbohydrate, protein and fat metabolism, and other activities that are inseparably linked to these. • Actions include- • Carbohydrate & protein metabolism- promote glycogen deposition in liver, increase uric acid secretion, maintains blood glucose levels during starvation so that brain continues to get its nutrients. • Fat metabolism- promote lipolysis, subcutaneous tissue over extremities loses fat- moon face, fish mouth, buffalo hump • Calcium metabolism- inhibit intestinal absorption and enhance renal excretion of calcium • Water excretion- maintain normal GFR • CVS- restrict capillary permeability, maintain tone of arterioles and myocardial contractility.
  23. 23. • Skeletal muscles- optimum level needed for normal muscular activity- Hypocorticism- diminished work capacity and weakness due tohypodynamic circulation Hypercorticism- muscle wasting and myopathy weakness • CNS- pharmacological doses- mild euphoria- insomnia, anxiety or depression • Stomach- aggrevate peptic ulcer • Inflammatory responses- irrespective of type of injury, inflammatory response suppressed. • Action is non-specific, reduction of increased capillary permeability, local exudation, cellular infiltration, phagocytic activity and late responses like capillary proliferation, collagen deposition, fibroblastic activity and scar formation, limits recruitment of inflammatory cells at local site.
  24. 24. • Post treatment pain or flare-up after endodontic treatment  inflammation, infection, or both in the periradicular tissues. • Establishing patency and subsequently debriding and shaping the root canal system  irritate the periradicular tissues  introduce bacteria, bacterial products, necrotic pulp tissue, or caustic irrigating solution through apical foramina. • In response to this irritation  inflammatory mediators (e.g., prostaglandins, leukotrienes, bradykinin, platelet-activating factor, substance P, etc.)  released into the tissues surrounding the apical area of the tooth. • Pain fibers are directly stimulated or sensitized, and an increase in vascular dilation and permeability results in edema and increased interstitial tissue pressure.
  25. 25. Glucocorticosteroids reduce the acute inflammatory response by • suppressing vasodilation, • migration of polymorphonuclear (PMN) leukocytes • phagocytosis • inhibiting formation of arachidonic acid from neutrophil and macrophage cell membrane phospholipids, thus blocking the COX and lipoxygenase pathways and respective synthesis of PGs and leukotrienes.
  26. 26. • Wolfson and Blitzer stated that hydrocortisone as an intracanal medication resulted in reduction and elimination of inflammatory reactions in periapical tissues. • Ehrmann reported that ledermix (triamcinolone dimethyl chlorotetracycline in a water soluble cream) stopped the pain associated with pericementitis. • Langeland et al demonstrated that Ledermix as an intracanal medication eliminated post-endodontic treatment pain within minutes to a few hours after placement. • Chance et al compared the effect of intracanal meticortelone (prednisolone acetate 2.5%) vs. saline on post-treatment pain in a double-blind study. • The results indicated that the corticosteroid was effective significantly in reducing the incidence of pain in vital teeth when compared to saline. • However, there was no difference between the two solutions in necrotic teeth.
  27. 27. Ledermix • Ledermix is a paste that combines 1% triamcinolone acitonide (a corticosteroid) and demethylchlorotetracycline (demeclocycline, a tetracycline analog). • Used as a pulp capping agent, and as a root canal medicament for both vital and necrotic cases because of its anti-inflammatory and antimicrobial properties. • Both components of Ledermix can diffuse into dentin and through the apical foramen. • The concentration of demeclocycline in the root canal was shown to be much higher than is required to inhibit bacteria; however, this activity tends to decrease considerably by 7days.
  28. 28. • It may be combined with calcium hydroxide at a 50:50 ratio to enhance its antimicrobial efficacy, but this tends to reduce the diffusion of its main ingredients. • Efficacious against pulpal pain in some earlier studies, possibly because of its corticosteroid content; however, pulp capping for painful cases with pulp exposures is not currently recommended because of its low long-term prognosis. • In a randomized clinical trial to compare Ledermix with formocresol and calcium hydroxide used as interappointment medicaments on postinstrumentation flare-ups, no differences were detected among the three medicaments.
  29. 29. Intracanal Administration • In 50 consecutive patients requiring nonsurgical root canal treatment of vital teeth, one investigator alternately placed a dexamethasone solution or saline placebo as intracanal medicaments after the root canals had been cleaned and shaped. Pretreatment pain ratings were collected, and at 24, 48, and 72 hours after treatment. Results indicated a significant reduction in pain at 24 hours but no, significant difference at 48 and 72 hours. Intracanal steroids appear to have significant effects for reducing postoperative pain. Moskow A, et al: Intracanal use of a corticosteroid solution as an endodontic anodyne. Oral Surg Oral Med Oral Pathol 58:600, 1984.
  30. 30. Systemic Administration In one double-blind, randomized, placebo-controlled study, dexamethasone (4 mg/ml) or saline was injected intramuscularly at the conclusion of a single-visit endodontic appointment or at the first visit of a multivisit procedure. Results indicated that the steroid significantly reduced the incidence and severity of pain at 4 hours when compared with the placebo. Pain was reduced at 24 hours, but it was not statistically significant, and no difference in incidence or severity was seen at 48 hours 106 patients with irreversible pulpitis and acute periradicular periodontitis were given an intraoral intramuscular injection of dexamethasone at different doses, either on completion of a single-visit endodontic treatment or after the first visit of a multivisit procedure. Systemic administration of dexamethasone was shown to significantly reduce the severity of pain at 4 and 8 hours, with an optimum dose between 0.07 and 0.09 mg/kg. No significant reduction in the severity of pain was noted at 24, 48, and 72 hours, and no overall effect was seen on the incidence of pain.
  31. 31. Another study compared the effect on intraligamentary injection of methylprednisolone, mepivacaine, or placebo in preventing posttreatment endodontic pain. The results showed methylprednisolone significantly reduced postoperative pain within a 24-hour follow-up period In a double-blind placebo controlled study, patients with irreversible pulpitis were given 4 mg of dexamethasone or placebo by means of a supraperiosteal injection at the apex of the treated tooth following pulpectomy. This is an injection technique that most clinicians would be familiar with (as opposed to intramuscular injection). Posttreatment pain was significantly reduced in the steroid group during the first 24 hours. There was no difference at 48 hours.
  32. 32. Collectively, these studies on systemic steroid administration indicate that corticosteroids reduce the severity of posttreatment endodontic pain compared with placebo treatment. ‘However, given the relative safety/efficacy relationship between steroids and NSAIDs, most investigators choose an NSAID as the drug of first choice for postoperative pain control.’
  34. 34. Endodontics in the adult patient: the role of antibiotics L.P. Longmana, A.J. Preston, M.V. Martin, N.H.F. Wilson Journal of Dentistry 28 (2000) 539–548
  35. 35. • The first reported local use of an antibiotic in endodontics was in 1951 when Grossman used a polyantibiotic paste known as PBSC (a mixture of penicillin, bacitracin, streptomycin, and caprylate sodium). • PBSC contained penicillin to target Gram-positive organisms, bacitracin for penicillin resistant strains, streptomycin for Gram- negative organisms, and caprylate sodium to target yeasts - these components were suspended in a silicone vehicle. • Later, Nystatin replaced caprylate sodium as an antifungal agent in a similar medicament, known as PBSN.
  36. 36. Bacteria are involved in endodontic cases with apical periodontitis, the incidence of a posttreatment infection or flare-up is a concern to clinicians providing endodontic treatment. Use of antibiotics is controversial for several reasons. 1. overprescribing antibiotics, especially when these drugs are not indicated, has led to increased bacterial resistance and patient sensitization. 2. antibiotics have been mistakenly prescribed for patients with severe pain who have a vital tooth (i.e., when bacteria are unlikely to be a causative factor in periradicular pain). 3. even when bacteria are likely to be present, data from controlled clinical trials provide little or no support for the hypothesis that antibiotics reduce pain.
  37. 37. • Antibiotic usage in endodontic therapy is almost totally empirical driven by opinion and medico-legal concerns. • The rational use of antibiotics is based upon three variables: - a defined indication - the appropriateness of the antibiotic, and - the adverse effects associated with the drug. Antibiotics are prescribed in endodontic practice for either therapeutic or prophylactic purposes.
  38. 38. Penicillins • Penicillins have a short half-life, limited to about 1 hour. • Amoxicillin is generally considered the penicillin of first choice because of its somewhat better absorption from the gut. • Also used for periodontal abscesses, periapical abscesses, pericoronitis, acute suppurative pulpitis, necrotizing ulcerative gingivitis, oral cellulitis etc • Less active against Shigella and H.influenza • Majority of cases resolve with 250-500 mg TDS given for 5 days.
  39. 39. Cephalosporins • Obtained from fungus Cephalosporium. 4 generations- First generation- high activity against gram +ve, weak against gram –ve • Cefazolin, cephalexin, cephradine, cefadroxil Second generation- more active against gram -ve • Cefaclor, cefuroxime Third generation- highly augmented activity against gram –ve enterobacteriaceae, some inhibit pseudomonas, less active on gram positive cocci and anaerobes • Cefixime, cefdinir, cefotaxime, ceftizoxime, cefoperazone Fourth generation- highly resistant to B-lactamases, active against many bacteria resistant to earlier drugs. P.aeruginosa and staph.aureus also inhibited. • Cefepime, cefpirome • All bactericidal, same mechanism of action as penicillin, i.e inhibition of bacterial cell wall synthesis.
  40. 40. Metronidazole • Metronidazole (Flagyl®) is also considered a bactericidal drug because of its fast killing time. • It attacks the bacteria’s DNA and works against obligate anaerobes but not against facultative bacteria or aerobes. • Metronidazole is often used in combination with another antibiotic, usually amoxicillin, to combat the stomach ulcer– causing Helicobacter pylori. • Combination helps in severe dental infections • Metronidazole shares properties with disulfiram (Antabuse®), a drug used to help alcoholics avoid alcohol by inducing violent vomiting. Patients taking metronidazole should be cautioned about not using alcohol for the time they are taking the drug plus 1 day following to allow the drug to be eliminated from their system. • The half-life of metronidazole is in the 8- to 10-hour range. Side effects include an unpleasant, metallic taste and brown discoloration of the urine, effects that are dose related.
  41. 41. Macrolides • Erythromycins kill bacteria by slowing the manufacture of bacterial protein but do not alter the rate of human protein synthesis. • Alternative to penicillin • Act by inhibiting bacterial protein synthesis • Narrow spectrum, mostly gram +ve, few gram –ve, highly active against Str.pyogens, Str.pneumonia, N.gonorrhoeae etc • Acid labile, enteric coated tablets to protect it from gastric acid, crosses serous membranes and placenta but not blood brain barrier. • Plasma t1/2 is 1.5 hours • Dose- 250-500 mg 6 hourly • Adverse effects- GIT- diarrhoea, epigastric pain, high doses- hearing impairment, hypersensitivity • Second choice drug to penicillins in dental infections, valuable to patients allergic to penicillins
  42. 42. Azithromycin- expanded spectrum, better tolerability, improved pharmacokinetics. • More active than other macrolides against H.influenza, Peptostreptococcus, Clostridia • Less active against gram +ve cocci • Acid stability, rapid oral absorption, marked tissue distribution and intracellular penetration. • Absorption decreased by food • Dose- azithral 500 mg once daily 1 hour before or 2 hours after food for 3 days is sufficient for most infections • Mild gastric upset, abdominal pain, headache and dizziness
  43. 43. Clindamycin (Cleocin®) often indicated in endodontic infections. • It is rapidly and completely absorbed and has a good spectrum of killing oral pathogens, including many anaerobes. • It was, however, the first antibiotic to be associated with causing pseudomembranous colitis, a life-threatening condition in which large patches of gut slough epithelium because of toxins from overgrowth of the nonsusceptible organism Clostridium difficile. • The average half-life of clindamycin is about 3 hours.
  44. 44. Tetracyclines • Tetracyclines, including tetracycline-HCl, minocycline, demeclocycline and doxycycline, are a group of broad-spectrum antibiotics that are effective against a wide range of microorganisms. • Bacteriostatic in nature. • This property may be advantageous because, in the absence of bacterial cell lysis, antigenic byproducts such as endotoxin are not released. • Inhibition of mammalian collagenases, which prevent tissue breakdown. • Inhibition of clastic cells, which results in anti-resorptive activity • In endodontics, tetracyclines have been used to remove the smear layer from instrumented root canal walls, for irrigation of retrograde cavities during periapical surgical procedures, and as anintracanal medicament.
  45. 45. • Barkhordar et al. evaluated the effect of doxycycline-HCl on the smear layer of instrumented root canal walls. They showed that doxycycline-HCl eliminated smear layer in a concentration dependent manner with 100 mg/ml doxycycline being more effective than lower concentrations. • In another investigation, Haznedaroglu and Ersev used scanning electron microscopy (SEM) to assess the effect of tetracycline-HCl as an endodontic irrigant in removing the smear layer. They reported that tetracycline was as effective as citric acid in removing the smear layer. • Barkhordar and Russell evaluated the effect of doxycycline on the apical penetration of dye through the margins of retrograde fillings. The teeth with retrograde IRM or amalgam fillings placed subsequent to doxycycline irrigation had significantly less dye penetration than those that were not irrigated with doxycycline.
  46. 46. • Carson et al. used an agar diffusion test to compare the antimicrobial activities of 6% and 3% sodium hypochlorite (NaOCl) solutions, 2% and 0.12% chlorhexidine gluconate (CHX), and 0.01% and 0.005% doxycycline (Doxy) on four microorganisms associated with endodontic infections of teeth that had not been previously treated, namely Peptostreptococcus micros, Prevotella intermedia, Streptococcus sanguis, and Lactobacillus acidophilus. For the first three of these organisms, the general order of antimicrobial effectiveness was 0.01% Doxy >0.005% Doxy >6% NaOCl >3% NaOCl >2% CHX > 0.12% CHX However, for L. acidophilus, the order of effectiveness was 6% NaOCl >3% NaOCl >2% CHX > 0.01% Doxy >0.005% Doxy >0.12% CHX.
  47. 47. • Pinheiro et al. evaluated the antibiotic susceptibility of Enterococcus faecalis isolates from canals of root-filled teeth with periapical lesions. • The antibiotics were benzylpenicillin, amoxicillin, amoxicillin with clavulanic acid, erythromycin, azithromycin, vancomycin, chloramphenicol, tetracycline, doxycycline, ciprofloxacin and moxifloxacin. • The vast majority (85.7%) of the isolates were susceptible to tetracycline and doxycycline. • Chai et al. investigated the antimicrobial efficacy of six groups of antibiotics (ampicillin co-trimoxazole, erythromycin, oxytetracycline, vancomycin, and vancomycin followed b gentamicin) and calcium hydroxide agains Enterococcus faecalis biofilm in a membrane filter model. • They concluded that erythromycin, oxytetracycline and Ca (OH)2 were 100% effective in eliminating the E. faecalis biofilm, whereas ampicillin, co-trimoxazole, vancomycin, and vancomycin followed by gentamicin were ineffective.
  48. 48. Based on the hypotheses that microorganisms can reach the apical area of recently replanted teeth from the oral cavity (or from contaminated root surfaces during the extra-oral time), and that tetracyclines can potentially inhibit this route of bacterial contamination, Cvek et al. developed a protocol for the topical treatment of exposed roots with doxycycline before replantation. • Aim was to eliminate the microorganisms from the root surface of an avulsed tooth via direct local application of the antibiotic in order to decrease the frequency and severity of the inflammatory response. • Topical doxycycline significantly increased the chances of successful pulp revascularization and decreased the number of microorganisms that could be isolated from the root canals. • They also reported a decreased frequency of ankylosis, external replacement resorption and external inflammatory resorption. • The beneficial effect of soaking a tooth in doxycycline has also been confirmed by Yanpiset and Trope
  49. 49. Substantivity of tetracyclines • Tetracyclines readily attach to dentine and are subsequently released without losing their antibacterial activity. • This property creates a reservoir of active antibacterial agent, which is then released from the dentine surface in a slow and sustained manner. • Stabholz et al. compared the antibacterial substantivity of two concentrations of tetracyclineHCl (50 mg/ml, 10 mg/ml) and 0.12% chlorhexidine. • Their findings showed that both concentrations of tetracycline demonstrated residual antibacterial activity and the antibacterial substantivity of the three solutions in descending order was: 50 mg/ml tetracycline >10 mg/ml tetracycline > 0.12% CHX. • Abbott et al. demonstrated that tetracyclines form a strong reversible bond with the dental hard tissues and that they exhibit slow release over an extended period of time up to at least 12 weeks.
  50. 50. BioPure (MTAD) • Bio Pure (Dentsply, Tulsa Dental, Tulsa, OK, USA), otherwise known as MTAD (mixture of tetracycline, acid and detergent), is a relatively new root canal irrigant which was introduced by Torabinejad and Johnson in 2003. • This solution contains 3% doxycycline (at a concentration of 3%), citric acid (4.25%) and a detergent, Polysorbate 80 (0.5%). • Several studies have evaluated the effectiveness of MTAD for disinfection of root canals. • Torabinejad et al have shown that MTAD is able to remove the smear layer and is effective against E. faecalis. • Shabahang et al. cleaned and shaped root canals of extracted human teeth and exposed them to human saliva. They then compared the antibacterial efficacy of a combination of 1.3% NaOCl as a root canal irrigant and MTAD as a final rinse with that of 5.25% NaOCl. Their findings showed that using MTAD in addition to 1.3% NaOCl was more effective at disinfecting root canals than using 5.25% NaOCl alone.
  51. 51. • Tay et al. found that when MTAD was applied to 1.3% NaOCl- irrigated dentine, its antimicrobial substantivity was reduced. They attributed this to the oxidation of MTAD by NaOCl in a manner similar to the peroxidation of tetracycline by reactive oxygen species. • Shabahang and Torabinejad compared the antibacterial effects of MTAD with those of NaOCl and EDTA by using standard in vitro microbiological techniques and they reported that MTAD was significantly more effective against E. faecalis.
  52. 52. • Kho and Baumgartner compared the antimicrobial efficacy of 1.3% NaOCl /MTAD against E faecalis with that of the combined alternate use of 5.25% NaOCl and 15% EDTA for root canal irrigation. • This investigation showed consistent disinfection of infected root canals when a combination of 5.25% NaOCl and 15% EDTA was used. • However, the combination of 1.3% NaOCl/ MTAD left nearly 50% of the canals contaminated with E. faecalis. • Mohammadi and Yazdizadeh evaluated the substantivity of NaOCl, CHX and MTAD substantivity of MTAD was significantly greater than CHX and NaOCl.
  53. 53. Tetraclean • Tetraclean (Ogna Laboratori Farmaceutici, Muggiò(Mi), Italy), like MTAD, is a mixture of an antibiotic, an acid and a detergent. However, the concentration of the antibiotic, doxycycline (50 mg/ml), and the type of detergent (polypropylene glycol) differ from those of MTAD. • Giardino et al.compared the surface tension of 17% EDTA, Cetrexidin, Smear Clear, 5.25% NaOCl, MTAD and Tetraclean. • The NaOCl and EDTA had the highest surface tension, whereas Cetrexedin and Tetraclean had the lowest values. • In another study, they compared the antimicrobial efficacy of 5.25% NaOCl, MTAD, and Tetraclean against an E. faecalis biofilm generated on cellulose nitrate membrane filters. • Only the NaOCl could disaggregate and remove the biofilm at every time interval tested although treatment with Tetraclean caused a high degree of biofilm disaggregation at each time interval when compared with MTAD.
  54. 54. Combination of Ledermix and calcium hydroxide • The combination of Ledermix paste with calcium hydroxide was advocated by Schroeder initially for the treatment of necrotic teeth with incomplete root formation. • A 50:50 mixture of Ledermix paste and calcium hydroxide has also been advocated as an intracanal dressing in cases of infected root canals. • It has been shown that the 50:50 mixture results in slower release and diffusion of the active components of Ledermix paste, which makes the medicament last longer in the canal. • This in turn helps to maintain the sterility of the canal for longer and also maintains a higher concentration of all components within the canal.
  55. 55. • Seow showed that for Streptococcus sanguis and S. aureus, the addition of only 25% by volume of Calyxl (a calcium hydroxide in saline paste) (Otto and Co. Frankfurt, Germany) to Ledermix converted the zone of complete inhibition originally seen in Ledermix to one of only partial inhibition. • Chu et al. compared the efficacy of disinfection of root canals with periapical radiolucencies when treated with either antibiotics/ steroid medicaments (Ledermix or Septomixine) or a calcium hydroxide paste (Calasept, Speiko, Darmstadt, Germany). • Their finding showed that in the Ledermix group, 38 strains of bacteria were recovered. The Septomixine group had 25 strains, and the Calasept group had 25 strains. • Gram-positive facultative anaerobic cocci (including staphylococci and streptococci) were more prevalent than the gram-negative obligate anaerobic rods after treatment in all three groups.
  56. 56. Septomixine Forte • Septomixine Forte (Septodont, Saint- Maur, France) contains two antibiotics: Neomycin and Polymixin B sulfate. • Tang et al. who demonstrated that a routine one-week application of Septomixine Forte was not effective in inhibiting residual intracanal bacterial growth between appointments. • In addition, although the anti-inflammatory (corticosteroid) agent, dexamethasone (at a concentration of 0.05%), is clinically effective, triamcinolone is considered to have less systemic side effects.
  57. 57. Triple antibiotic paste • The infection of the root canal system is considered to be a polymicrobial infection, consisting of both aerobic an anaerobic bacteria. • Because of the complexity of the root canal infection, it is unlikely that any single antibiotic could result in effective sterilization of the canal. • More likely a combination would be needed to address the diverse flora encountered. • A combination of antibiotics would also decrease the likelihood of the development of resistant bacterial strains. • The combination that appears to be most effective consists of metronidazole ciprofloxacin, and minocycline.
  58. 58. • Sato et al. evaluated the potential of a mixture of ciprofloxacin, metronidazole and minocycline to kill bacteria in the deep layers of root canal dentine in situ. • Results showed that no bacteria were recovered from the infected dentine of the root canal wall 24 h after application of the drug combination, except in one case in which a few bacteria were recovered. • Hoshino et al. investigated the antibacterial effect of a mixture of ciprofloxacin, metronidazole, and minocycline with and without the addition of rifampicin, on bacteria from infected dentine of root canal walls. • The efficacy was also determined against bacteria of carious dentine and infected pulps, which may the precursory bacteria of infected root dentine. • They found that alone, none of the drugs resulted in complete elimination of bacteria. However, in combination; these drugs were able to consistently sterilize all samples.
  59. 59. • Iwaya et al. reported a necrotic immature mandibular second premolar with periapical involvement and sinus tract. • Instead of the standard root canal treatment protocol and apexification, antimicrobial agents (metronidazole and ciprofloxacin) were used in the canal, after which the canal was left empty. • Radiographic examination showed the start of apical closure five months after the completion of the antimicrobial protocol. • Thickening of the canal wall and complete apical closure was confirmed 30 months after the treatment, indicating the revascularization potential of a young permanent tooth pulp into a bacteria-free root canal space.
  60. 60. Takushige et al. evaluated the efficacy of polyantibiotic paste consisted of metronidazole, ciprofloxacin, and minocycline, on the clinical outcome of so-called “Lesion Sterilization and Tissue Repair,” (LSTR) therapy in primary teeth with periradicular lesions. Results showed that in all cases, clinical symptoms such as gingival swelling, sinus tracts, induced dull pain, spontaneous dull pain, and pain on biting disappeared after treatment, although in four cases clinical signs and symptoms were finally resolved only after retreatment using the same procedures. Thus, gingival abscesses and fistulae, if present, disappeared after a few days.
  61. 61. Endodontics and therapeutic antibiotics a. Adjunct to operative treatment In healthy patients  endodontic infections can be treated solely by the early establishment of drainage and removal of the cause of the problem, for example, debridement of the infected root canal system or surgical removal of extraradicular infection. 1. In acute dentoalveolar infections  antibiotics may be indicated because there is a diffuse spreading infection or evidence of systemic involvement. Antibiotics are not an alternative to dental intervention; they are an adjunct to it 2. In medically compromised patients  host-defence mechanisms may be thought to be inadequate  the operative treatment of acute dentoalveolar infections may sometimes be supplemented with therapeutic antibiotics. 3. A patient’s resistance to infection may be reduced by medication (e.g. corticosteroids, antimetabolites), systemic disease such as leukaemia, HIV or poorly controlled Type I diabetes
  62. 62. b. Contingency treatment On rare occasions, it may not be possible to obtain drainage or remove the cause of infection by operative treatment. There is no evidence that the use of antibiotics in this situation is of any benefit; definitive treatment is required. The principle purposes of prescribing are to: limit the local spread of infection, treat systemic infection and bring about symptomatic relief Examples 1. Patient has cellulitis associated with an acute periapical infection, originating from a tooth that has a well-retained intraradicular post  drainage of infection cannot be achieved by the incision of the soft tissues and intracanal instrumentation. 2. Failure to achieve anaesthesia for the extraction of an abscessed tooth can necessitate a prescription for antimicrobials in acute periapical infection. 3. When an anxious or phobic patient presents with acute periapical infection, and cannot accept treatment without the assistance of sedation. 4. Uncooperative patients with physical or learning disabilities may not be amenable to immediate operative treatment.
  63. 63. c. Antibiotics at obturation • Anecdotal evidence cites the use of systemic antibiotics at the time of obturation, when pus remains in the root canal system, despite repeated inter-appointment dressings. • There is no scientific evidence that this practice is beneficial. • Antibiotic therapy has also been suggested for one visit endodontics, undertaken when there is infection present in the root canal. • There is no evidence that antibiotics are efficacious in this situation, the root canal is dressed rather than obturated.
  64. 64. d. Antibiotics for perio-endo lesions • There are no authoritative studies to support the use of systemic antibiotics in the management of “perio-endo” lesions. • The treatment of combined lesions is based upon the basic principles of endodontic and periodontal therapy, and is dependent upon the aetiology of the condition. • Endodontic treatment usually involves root canal treatment, or less commonly root resection or repair of a perforation. • Systemic antibiotics are not a substitute for effective mechanical debridement of the root canal system and root surface.
  65. 65. Which antibiotic? • At least 70 different bacterial species have been isolated from root canals and synergistic relationships are thought to exist between them. • Certain bacteria seem to occur in pairs and these include: Bacteroides vulgaris and Fusobacterium necrophorum; Peptostreptococcus spp. and Prevotella spp; P. micros and P. melaninogenica; Prevotella and Eubacterium ssp. • The majority of symptomatic, infected root canals contain anaerobes; it has been proposed that the larger the number of bacterial species present the more symptoms will be experienced. • It has also been demonstrated that intracanal flora from teeth with failed endodontic therapy differs markedly from the root canals of untreated teeth.
  66. 66. • Empirical prescribing of anti-microbials as part of endodontic management is problematic, given the diversity of potential pathogens and their differing drug sensitivities. • Culture and sensitivity testing is not routinely recommended for endodontic procedures The most commonly prescribed antibiotics are erythromycin, amoxicillin, penicillin and metronidazole Some anaerobes isolated from the endodontic lesions are resistant to penicillin and therefore serious infections are treated empirically with a combination of metronidazole and a penicillin
  67. 67. Duration of antibiotic therapy required for acute dentoalveolar infections has never been defined precisely. • Tendency in dental practice to use courses of antibiotics  3–5 days for the treatment of infection . • There is increasing awareness of the value of the commensal flora in the host’s defence system both in the oral cavity and in other body sites. • Prolonged courses of antibiotics destroy the commensal flora and abolish colonisation resistance. • The prescribing of systemic antibiotics must therefore be justifiable.
  68. 68. Few studies on the use of antimicrobials have supported the view that it is not necessary to complete the course of antibiotics. • One study has advocated that a two-dose administration of an anti- microbial agent is as efficacious as a 5 day course in the management of acute dentoalveolar infections; this was not a double blind placebo controlled trial. • Two separate investigations, compared three anti-microbial agents, and showed that the majority of patients were asymptomatic after 2 days therapy. • Majority of patients 2 or 3 days of oral antibiotics, in doses recommended by the BNF, will suffice for acute dentoalveolar infections. • Alternatively, a two-dose regime of 3 g amoxicillin can be used in patients who are not allergic to penicillin. • Fazakerley MW, McGowan P, Hardy P, et al. A comparative study of cephradine, amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar infections. British Dental Journal1993;174:359–63. • Martin MV, Longman LP, Hill JB, et al. Acute alveolar infections: an investigation of the duration of antibiotic therapy. British Dental Journal 1997;183:135–7.
  69. 69. Topical antibiotics and endodontics The limited spectrum of activity of the antibiotic preparations available, the potential for bacterial resistance, the risk of drug hypersensitivity and the potential to mask certain aetiological factors limit their usefulness. Pulpitis There is no convincing evidence to justify the use of Ledermix (Lederle Lab Gosport, Hants, UK) to sedate the pulp prior to definitive treatment. There is no indication for the use of topical antibiotics in the treatment of pulpitis Pulp capping Calcium hydroxide- most popular agent for both direct and indirect pulp capping. Anti-bacterial action, stimulates secondary dentine formation. Ledermix is the most commonly used alternative to calcium hydroxide and contains a steroid (triamcinolone) and an antibiotic (demethylchlortetracycline). Ledermix is a topical preparation, available as either a paste or a cement.
  70. 70. Root canal therapy • The most important elements of root canal preparation are effective access and aseptic biomechanical preparation. • Early investigations evaluated two antibiotic-containing preparations: Grossman’s polyantibiotic paste, which contains penicillin, bacitracin or chloramphenicol and streptomycin • A mixture of neomycin, polymixin and nystatin. • Both of these had some efficacy as intracanal medicaments. Perio-endo lesions Topical antibiotics, such as the tetracyclines or metronidazole, may be applied by some clinicians, to the periodontal defect as an adjunct to root planing.
  71. 71. Flare-ups • Topical antibiotics have been used to reduce post-operative pain and swelling following root canal preparation; this is often referred to as a flare- up. • In the treatment of infected root canals where there is often a need to carry out the treatment over more than one visit, with an antibacterial intracanal medicament placed between visits; the intracanal medicament that is commonly used is calcium hydroxide. Tooth avulsion Ledermix has been used as an intracanal medicament in the management of tooth avulsion, but it is not clear whether the beneficial effect is due to the action of the steroid or the antibiotic.
  72. 72. Antibiotic prophylaxis and endodontics Healthy patient There is no evidence that antibiotic prophylaxis, given to healthy patients undergoing surgical endodontics is efficacious. Despite this, antibiotics are sometimes prescribed prophylactically to prevent infection at the site of surgery. • Ideally, antibiotics should be given prior to reimplantation. • Often not possible and could necessitate a delay in tooth replacement, adversely affecting the prognosis. • Re-implantation is therefore, one of the rare situations when chemoprophylaxis may have to be given post-operatively, assuming there are no medical contraindications
  73. 73. • The re-implantation of teeth should not be considered if the procedure places the patient at risk from haematogenous spread of infection. • An example would be a patient with acute leukaemia or HIV infection. • Once the decision to re-implant has been made, the timing of antibiotic prophylaxis is critical if serious sequelae are to be avoided. • It would be logical to administer antibiotic prophylaxis prior to implantation, to ensure adequate antibiotic serum levels at the time of operation.
  74. 74. Prophylaxis for the medically compromised • Patients who are susceptible to IE, or osteoradionecrosis, and those who have endoprostheses • Second category is patients with impaired host-defence mechanisms • These patients are potentially at risk from opportunistic infections. • Patients who are receiving renal dialysis or have had organ transplants are included in this group. Infective endocarditis • Dental procedures that reliably cause a transient bacteraemia could result in IE. • The use of chemoprophylaxis is well established and necessary medico-legally for surgical endodontics, in patients at risk from IE.
  75. 75. • It is unrealistic and undesirable to give systemic prophylaxis for every endodontic procedure that may occasionally cause bleeding or a bacteraemia, including the placement of rubber dam. • Simple pre-operative mouthrinsing and disinfection of the gingival tissues with chlorhexidine reduces the magnitude of a bacteraemia • Elective endodontic procedures should be avoided wherever possible, in patients who have a damaged endocardium and concomitant gingival inflammation.
  76. 76. Radiotherapy • After radiotherapy, there is a diminution of the vascular supply in the irradiated area especially in the mandible. • This is a progressive risk that does not reduce with time • Risk of infection is much greater with exodontia than root canal therapy, consequently non-surgical endodontics is the preferred treatment for a necrotic pulp in irradiated patients. Prosthetic implants • The prophylactic antibiotics should target the putative pathogens, staphylococci and to a lesser extent oral streptococci • Patients with cardiac pacemakers, intraocular lenses, breast implants, penile implants and prosthetic vascular grafts are not considered to be especially susceptible to infection from dental bacteraemias. • The use of antibiotic prophylaxis in patients with intravascular access devices and CSF shunts is contentious. • Neurosurgeons are more likely to recommend prophylaxis for patients with ventriculoatrial shunts, than for the more commonly used ventriculoperitoneal shunts
  77. 77. Immunocompromised patients • Patients who are immunocompromised, including patients who have organ transplants or indwelling intraperitoneal catheters, do not require antibiotic prophylaxis for dental treatment. • It can be concluded, therefore, that endodontic treatment does not require antibiotic prophylaxis. Systemic antibiotics should normally only be prescribed to treat dental infections on the basis of a defined need. • The potential benefits of antibiotic administration should therefore outweigh the possible disadvantages associated with their use. • A dentist who prescribes an antibiotic for a questionable indication may be seen as placing a patient at risk from potential adverse effects of drugs.
  79. 79. Local anesthetics (CLASSIFICATION): Injectable a. Short duration (30 minutes of pulpal anesthesia)- Procaine b. Intermediate duration (60 minutes of pulpal anesthesia)- Lignocaine, prilocaine c. Long duration (over 90 minutes of pulpal anesthesia)- Tetracaine, bupivacaine, ropivacaine, dibucaine Surface anesthetic Soluble Cocaine Lignocaine Tetracaine Benoxinate Insoluble Benzocaine Butylaminobenzoate ( Butamben)
  80. 80. Lignocaine (lidocaine) • Most widely used • Surface application and injectable • Blocks nerve conduction in 3 mins whereas procaine may take upto 15 mins • Overdose causes muscle twitching, convulsions, cardiac arrhythmias, fall in BP, coma, respiratory arrests • Dental use- 2% with or without adrenaline 1:80,000
  81. 81. Mepivacaine • Available in formulation containing levonordefrin, an adrenergic agonist, 1:20000 conc. Articaine • 4% solution containing 1:100,000 and 1:200,000 epinephrine • Amide anesthetic that contains thiophene ring and ester linkage. • Maximum dose is 7 catridges compared to 13 catridges of 2% lidocaine • Potential to cause methemoglobinemia and neuropathies
  82. 82. Bupivacaine and etidocaine • Prolonged pain control, long acting • Etidocaine withdrawn from market recently • Bupivacaine exhibits prolonged soft tissue numbness or lip sign • Slower onset than lidocaine but twice the duration of action (around 4 hours) in mandible Ropivacaine • Structural homologue of bupivacaine that appears to have a lower potential for CNS and CV toxic effects.
  83. 83. • Cardiac patients (e.g., those with unstable angina pectoris, history of myocardial infarction or stroke within the past 6 months, severe hypertension, uncontrolled congestive heart failure, or heart transplant) should not receive a local anesthetic containing a vasoconstrictor and should consult their physicians before undergoing endodontic treatment. • Local anesthetics may interact with a patient’s medications • Thorough review of the medical history is an absolute requirement. • Potential drug-drug interactions occur primarily with the vasoconstrictors in local anesthetic formulations. • Judicious use of local anesthetic solutions without vasoconstrictors (e.g., 3% mepivacaine) is a reasonable alternative for adult patients.
  85. 85. Antimicrobial agents may be disinfectants and antiseptics that destroy or inhibit the growth of microorganisms and thereby prevent infection by pathogenic or potentially pathogenic microorganisms. Disinfectants are used on inanimate objects or surfaces, whilst antiseptics are used on living tissues. McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action, and resistance. Clinical Microbiology Reviews 1999;12:147–79.
  86. 86. Conventional antiseptics 1. Alcohols – Ethyl alcohol, Isopropylalcohol 2. Phenolic Compounds – Camphorated phenol, Monochlorophenol, Thymol, Cresol, Creosote 3. Heavy Metal Salts 4. Cationic Detergents – Quarternary ammonium compounds 5. Halogens – Hypochlorite, Chloramine T, Iodine, Iodophores Chemotherapeutics Antibiotics Classification of antimicrobial agents.
  87. 87. • The mechanism of action of antimicrobial agents is varied as they have multiple sites of action except for antibiotics, which have very specific sites of action. • The nature of the organism, antimicrobial agent and the concentration determine the response of the microorganisms to the antimicrobials. • The cell wall, cytoplasmic membrane and ribosomes of vegetative cells, the coat and cortex of bacterial spores, envelope and capsid of viruses and proteins (structural proteins, enzymes), nucleic acids and polysaccharides are some of the sites of action of antimicrobial agents. • These antimicrobial actions eventually result in the loss of important cell functions like protein synthesis and metabolism, replication, transcription and destruction of cell membranes with leakage of cell contents Mechanism of action
  88. 88. • The two most important features which determine the efficacy of antimicrobial agents are the killing and the cleaning potential of the agent. • The antimicrobial activity may vary from inhibition of metabolism to destruction of the microorganisms. • The specific target of action of antimicrobials is difficult to elucidate as antimicrobial agents act on multiple cell components, resulting in both primary and secondary effects, which in turn is hard to distinguish.
  89. 89. Sodium hypochlorite • Concentrations ranging from 0.5 % to 5.25 %. • This is due to its antimicrobial and dissolving effects on necrotic tissues (Sodium hypochlorite is a reducing agent with 5 % of available chlorine • lubricant, antiseptic agent, bleach and also dissolves tissue • Antibactericidal ability of NaOCl results from the formation of hypochlorous acid (HOCl) when in contact with organic debris. • HOCl exerts its effect by the oxidation of sulphydryl groups within bacterial enzyme systems, thereby disrupting the metabolism of the microorganism. • Cvek M et al. in his study reported that flushing with sterile saline had poor antibacterial action (9 %) when compared to sodium hypochlorite (25 %)
  90. 90. • The antibacterial action of NaOCl is time dependent. • In an in vivo study, Ringel et al. noted that in root canals of permanent teeth 2.5 % NaOCl had a more powerful antibacterial effect than 2 % chlorhexidine gluconate, as NaOCl was a powerful solvent for necrotic and organic material. • Naenni et al reported that only sodium hypochlorite showed effective necrotic tissue dissolution among 10 % chlorhexidine, 3 % and 30 % hydrogen peroxide, 10 % peracetic acid, 5 % dichloroisocyanurate (NaDCC), and 10 % citric acid.
  91. 91. Chlorhexidine gluconate • Chlorhexidine (CHX) is widely used in periodontal and endodontic treatment as an irrigant. • There are various mechanisms of antimicrobial action for chlorhexidine. • It attaches electrostatically to negatively charged sites on bacteria and also to its cytoplasmic membrane. • The leakage of intracellular material is due to the loss of osmotic balance by CHX. • The binding of CHX to hydroxyapatite and soft tissues changes their electrical field to compete with the binding of bacteria
  92. 92. Cetrexidin♦ (Vebas, San Giuliano, Milan, Italy) Antiseptic agent that is being evaluated. • It consists of 0.2 % chlorhexidine gluconate and 0.2 % cetrimide. • Cetrimide (cetiltrimethyl ammonium bromide), is a quarternery ammonium compound and a cationic detergent that is effective against many Gram positive and Gram negative bacteria
  93. 93. • Study on the antimicrobial effectiveness and cytotoxicity of 4 irrigant solutions, viz 5.25 % sodium hypochlorite (NaOCl), 0.2 % chlorhexidine gluconate plus 0.2 % cetrimide (CetrexidinR), 2 % chlorhexidine gluconate and 0.9 % sterile saline solution demonstrated that NaOCl should remain in the canal for a substantial period so that it can act upon the bacterial cells located in the irregularities within the canal. • In this study, 5 minutes following the irrigation process, chlorhexidine gluconate had a more rapid and stronger action on E. faecalis than NaOCl.
  94. 94. Calcium hydroxide • Calcium hydroxide is the most commonly used inter- appointment intracanal endodontic medicament. • The publication of research data on the antibacterial action of calcium hydroxide in root canal treatment by De Moor & De Witte led to increased use of calcium hydroxide in endodontic treatment. • The antibacterial activity is a result of free hydroxyl radical liberation and diffusion of hydroxyl radicals resulting in a highly alkaline environment(pH 12.5). • These hydroxyl ions penetrate the dentinal tubules and exert their effect.
  95. 95. • These hydroxyl radicals cause bacterial cell death by three possible mechanisms. • The first mechanism is by splitting DNA strands and thereby preventing DNA replication and disrupting cellular activity. • Another method is by lipid peroxidation, which leads to the destruction of both phospholipidand cell membrane, finally resulting in loss of unsaturated fatty acids and massive destruction of membrane. • The third mechanism is by protein denaturation and damage of cell metabolism. • Calcium hydroxide also shows increased activity against anaerobes in comparison to paramonochlorophenol and formocresol.
  96. 96. Hydrogen peroxide • The mechanism of action is by the reaction of superoxide ions, resulting in formation of hydroxyl radicals. • Hydroxyl radicals are strong oxidants and they destroy membrane lipids, DNA and other essential cell components. • The oxidation of sulphydryl groups and double bonds in proteins, lipids, and surface membranes is responsible for the antimicrobial action. • In addition, the chloride in the bacteria may be oxidized to hypochlorite when myeloperoxidase enzyme is present. • Hydrogen peroxide is an oxidizing solution and is usually used in combination with sodium hypochlorite for root canal irrigation. This results in two kinds of reactive oxygen species, the superoxide anion radical (O2 -) and the hydroxyl radical (OH-).
  97. 97. • Root canal irrigation with NaOCl and H2O2 induces both biological and mechanical effects. • The biological effect of NaClO and H2O2 owes to tissue irritation due to the chemical reactions of O2 - and OH-, while the mechanical effect results from O2 bubbling. • The effervescent action resulting in the release of nascent oxygen results in the agitation of the root canal contents and the debris is flushed out. • The tissue dissolution and antimicrobial effect are the main mode of action of the combined solutions. • The final irrigation of the canal should be done with sodium hypochlorite, as hydrogen peroxide can form gas in the presence of necrotic debris and blood leading to pain.
  98. 98. Formocresol • Formocresol consists of formalin and tricresol in a ratio of 1:1. • Tricresol is a combination of o-, m-, and p-cresols. • The application time and the concentration of formocresol influence the histologic reaction of vital pulp. • Formocresol is a bactericidal agent and the mode of action is by fixation, which results in inhibition of bacteria. • Formocresol causes zones of necrosis, fixation, and inflammation. • It results in healing with inflammation and eventual replacement with granulation tissue, bone or osteodentin in some cases.
  99. 99. Ferric sulphate • 15.5 % used as a haemostatic agent in pulpotomy procedures. • Landau and Johnsen in 1988 • The mode of action is by the formation of a ferric ion protein complex in the presence of blood resulting in the mechanical sealing of cut vessels by the membrane of this complex. • This ultimately leads to haemostasis • Pulpal reaction of ferric sulfate and formocresol did not differ from each other. • Ferric sulphate is less toxic than formocresol and hence it may be considered as an alternative to formocresol for pulp therapy in primary molars. • As ferric sulphate causes only haemostasis, it is a more appropriate pulpotomy agent and may be considered a good replacement for formocresol in pulpotomy.
  100. 100. Peracetic Acid • Peracetic acid has a wide spectrum of antimicrobial action at low concentration, and within short duration. • Aqueous solution of peracetic acid (PAA) has high microbicidal activity against a broad range of microorganisms. • Peracetic acid is an effective germicide against bacteria, yeast, and viruses at 0.03 % or lower concentration. • Alasri et al. state that when peracetic acid and hydrogen peroxide are used together, they have a combined action on biofilms owing to the microbicidal activity of peracetic acid and detachment of biofilm by hydrogen peroxide.
  101. 101. • The sporicidal action decreased with storage due to hydrolysis of peracetic acid, whereas it increased with high pH concentration. • The drawback of high pH concentration is the carcinogenic potential of 1 % peracetic acid, as it is a tumor promotor. • The sporicidal action in a study by Jose-Luis and Aylin was as follows: hypochlorite > peracetic acid > copper ascorbate > glutaraldehyde > peroxide > phenol > formaldehyde. • Ageing, pH, and temperature were found to greatly influence the order of the efficacy of these agents • According to Naenni N et al., among the commonly used endodontic irrigants like 10 % chlorhexidine, 3 % and 30 % hydrogen peroxide, 10 % peracetic acid, 5 % dichloroisocyanurate (NaDCC), and 10 % citric acid, all had lower tissue dissolution capacity in comparison to 1 % (wt/vol) sodium hypochlorite (NaOCl).
  102. 102. Chloramine T • Chloramine T is N-chloro-p-toluensulphonamidesodium. • It is used as an effective oral antiseptic agent. • The mode of action is by the conversion of amino acids into aldehydes, carbon dioxide, ammonia and nitriles. • Irrigation with a combination of hydrogen peroxide and chloramine, chloramine or glutaraldehyde were more effective irrigants than normal saline, 1% metronidazole or 3% hydrogen peroxide
  103. 103. Hexetidine 1,3-bis(2-ethylhexyl)-5-amino-5-methyl hexahydropyrimidine. • Hexetidine is a good antibacterial and antifungal agent with a wide spectrum of activity both in vivo and in vitro. • Hexetidine rinse is widely used as an antiplaque and antigingivitis, as it decreases supragingival plaque and gingival inflammation. • In vitro and in vivo action against Gram-positive and Gram- negative bacteria as well as yeasts (Candida albicans) is well known. • In addition, it is also used as an astringent, local anaesthetic and deodorant. • It has not been widely used in endodontic treatment. • Studies on in vitro oral biofilm models demonstrate that antimicrobials like chlorhexidine, hexetidine, delmopinol, amine fluoride/stannous fluoride, triclosan, and phenolic compounds interfere with bacterial metabolism and may inhibit biofilm development and maturation
  104. 104. Aminefluoride • 38 % diamine silver fluoride, or Ag(NH3)2F, is used as a Nd:YAG laser initiator. • Yokoyama K and co-workers reported that pulsed Nd:YAG laser or iontophoresis following Ag(NH3)2F increased the permeability of the root canal wall and occlusion of dentinal tubules. • Root canals treated using irradiation with an Nd:YAG laser that has been coated with Ag(NH3)2F solution showed improved results compared to either iontophoresis after coating with Ag(NH3)2F solution, or coating alone.
  105. 105. Cetylpyridinium chloride • Cetylpyridinium chloride (CPC) is a quaternary ammonium salt (C21H38ClN; molecular weight, 358.07) having a combination of hydrophilic and lipophilic affinities. • CPC is commonly used as a broad-spectrum antimicrobial against oral bacteria and with properties and uses typical of cationic surfactants. • The primary mechanism of action of CPC is by cell membrane penetration, which results in leakage of cell contents, disturbance of bacterial metabolism and inhibition of cell growth. • These eventually cause cell death. • It exhibits surface-active properties. • Thus the long duration of action is by virtue of the binding of CPC to the glycoproteins covering the teeth and oral mucosa.
  106. 106. • Cetylpyridinium chloride (CPC) is recognied as an effective antiplaque agent and commonly found in oral hygiene aids. • It is less commonly used in root canal treatment. • Several animal studies on the cytotoxicity of CPC have shown it to be a highly safe and effective antimicrobial agent. • CPC has the distinction of being recognized by the FDA Plaque Subcommittee after a six year review of over 40 active ingredients as being one of the only three (stannous fluoride and essential oils – the remaining two safe agents) antimicrobial agents which is safe and effective (concentration range of 0.05 and 0.10 %) for the treatment of plaque-induced gingivitis.
  108. 108. Most common fears of man- • Fear of height • Fear of flying • Fear of mice • Fear of public speaking • Fear of dentists ‘Our most common fears.’ Dental health advisor, Spring 1987
  109. 109. • Incidence of dental phobia or ODONTOPHOBIA- 10-30 % of adults, moderate to severe odontophobia • Fear and pain are a potent combination capable of provoking some of the most catastrophic situations imaginable in the dental office, such as cardiac arrest. • Sedation occurs as a result of CNS depression, from minimal sedation to general anesthesia.
  110. 110. • Minimal sedation- ‘anxiolysis’, a minimally depressed level of consciousness that retains the persons ability to independently and continuously maintain an airway and respond appropriately to physical stimulation or verbal command and that is produced by pharmacologic or nonpharmacologic method or a combination thereof. • Nitrous oxide/oxygen (N2O-O2) • Moderate sedation- ‘conscious sedation’, drug induced depression of consciousness during which pateints respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. • Deep sedation- drug induced depression of consciousness during which patients cannot be easily aroused but respond purposefully following repeated or painful stimulation.
  111. 111. • Sedation- Iatrosedation- ‘no drugs’ sedation, relaxation of the patient by the dentists behaviour. • Drug sedation/ techniques- • Inhalation sedation- • N20-O2, rapid onset of action, level of CNS depression that can be rapidly increased if necessary, level of CNS depression that can be rapidly decreased if necessary, complete recovery following the delivery of 100% O2 at the completion of procedure- permits the patient to leave the clinic unescorted, no other route of drug administration offers this advantage. • Because of rapid onset, it can be titrated, which increases both the safety and success of the technique. • Only disadvantage for endodontists is the nasal hood on the way which is not a problem once experienced.
  112. 112. Oral conscious sedation- • Least controllable route • Slow onset of action usually • Erratic absorption of the drug from the GIT • Only advantage is easy for dentist and patient • CNS depressants given night prior to planned appointment, in the morning 1 hr prior to the scheduled dental visit, to assist them in overcoming any last minute increase in their anxiety.
  113. 113. Generic name Proprietary name Dosage Benzodiazepines Alprazolam Niravam, Xanax 0.25-0.5 (max 4mg/day) Diazepam Valium 2-10 mg BID-QID Flurazepam Dalmane 15-30mg at bedtime Lorazepam Ativan 2-3mg/day BID-TID Midazolam Versed 0.25-1mg/kg pediatric Oxazepam Serax 15-30 tid-qid severe Triazolam Halcion 0.25 qhs Non-benzodiazepine anxiolytics Eszopiclone Lunesta 2mg qhs Zaleplon Sonata 10qhs insomnia Zolpidem Ambien 10 mg qhs Hypnotics Chloral hydrate 500 mg- 1 gm, max 2 gm/day Hydroxyzine Atarax 50-100 mg
  114. 114. Intravenous conscious sedation • Rapid onset, titration possible to desired level, more safer than oral • Requires fasting prior to procedure • Inability to quickly lessen the level of CNS depression • Inability to reverse the action of some drugs (barbiturates) • Prolonged clinical recovery • Benzodiazepines, midazolam, diazepam • Venipuncture skill required
  115. 115. Intramuscular • Drug by passes the GI tract, being absorbed directly into the system • Hepatic first pass effect neglected, leading to more reliable absorption and more rapid onset of action • Titration not possible • Doses decided by weight (mg/kg) • Reversal done with iv flumazenil or naloxone • Im not controllable like iv so sedation limited to moderate level, doctor should be trained to recognize and manage the patient entering deep sedation
  116. 116. Intranasal • Newer technique in dentistry • More rapid absorption since nasal mucosa is highly vascular • No injection needed • Cannot be titrated • Dosage based on weight • Sedation limited to moderate, not controllable • IN midazolam commonly used General anesthesia Provided to dentist by an anesthetologist
  118. 118. ‘Never treat a stranger.’ - Sir William Osler • The value of a thorough medical and dental history of a patient cannot be overemphasized. • Recognition of a medical condition that requires treatment modification prior to treatment can avert significant treatment complications.
  119. 119. ASA Physical Status Classification System & therapy modifications • ASA Physical Status 1 - A normal healthy patient No therapy modifications, stress reduction as indicated • ASA Physical Status 2 - A patient with mild systemic disease Possible stress reduction and other modifications as needed • ASA Physical Status 3 - A patient with severe systemic disease Possible stress modifications, stress reduction and medical consultation are priorities • ASA Physical Status 4 - A patient with severe systemic disease that is a constant threat to life Minimal emergency care in office, may consist of pharmacologic management only, hospitalize for stressful elective treatment, medical consultation urged • ASA Physical Status 5 - A moribund patient who is not expected to survive without the operation Treatment in the hospital is limited to life support only, eg:- airway and haemorrhage management • ASA Physical Status 6 - A declared brain-dead patient whose organs are being removed for donor purposes Not applicable
  120. 120. Antibiotic prophylaxis recommended, based on risk stratification for infective endocarditis Highest risk of adverse outcome from infective endocarditis • Prosthetic heart valve • Previous infective endocarditis • Congenital heart disease (CHD) • Unrepaired cyanotic CHD, including palliative shunts and conduits • Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or catheter, during the first six months after the procedure • Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device • Cardiac transplant recipients who develop cardiac valvulopathy Risk of dental procedure- All dental procedures that involve manipulation of gingival tissue or the periapical region of the teeth or perforation of the oral mucosa
  121. 121. Antibiotic prophylaxis for dental procedures- all regimens are a single dose given 30-60 mins before the procedure Standard oral regimen Adults- 2 gm amoxicillin Children- 50 mg/kg Alternative oral regimen for patients allergic to penicillin or patients who are currently taking a penicillin class antibiotic Adults- 2 gm cephalexin or 600 mg clindamycin or 500 mg azithromycin Children- 50 mg/kg cephalexin or 20 mg/kg clindamycin or 15 mg/kg azithromycin Patients unable to take oral medication Adults- 2 gm iv / im ampicillin or 1 gm im / iv cefazolin or ceftriaxone Children- 50 mg/kg im or iv ampicillin or 50 mg/kg im or iv cefazolin or ceftriaxone Alternative im/iv regimen for patients allergic to penicillin and unable to take oral medications Adults- 1 gm im/iv cefazolin or ceftriaxone or 600 mg im/iv clindamycin Children 50 mg/kg im/iv cephazolin or ceftriaxone 20 mg/kg im/iv clindamycin within 30 mins before the procedure
  122. 122. References BOOKS • Cohen’s Pathways of the pulp- 10th edition • Ingles Endodontics- 6th edition • Essentials of pharmacology- KD Tripathi, 2006 • Endodontics- Arnaldo Castellucci- Vol 1 and 2 • Endodontics- principles and practise- M.Torabinejad, 4th edition • Harty’s Endodontics in clinical practise, 6th edition ARTICLES • Pharmacological Strategies to Control Post-operative Endodontic Pain Zahed Mohammad, Alireza Farhad, Meisam Khalesi Dent Res J 2007; 4(2): 61-68 • Endodontics in the adult patient: the role of antibiotics L.P. Longman, A.J. Preston, M.V. Martin, N.H.F. Wilson Journal of Dentistry 28 (2000) 539–548 • Fazakerley MW, McGowan P, Hardy P, et al. A comparative study of cephradine, amoxycillin and phenoxymethylpenicillin in the treatment of acute dentoalveolar infections. British Dental Journal1993;174:359–63. • Martin MV, Longman LP, Hill JB, et al. Acute alveolar infections: an investigation of the duration of antibiotic therapy. British Dental Journal 1997;183:135–7.
  123. 123. • McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action, and resistance. Clinical Microbiology Reviews 1999;12:147–79. • Anaesthetising Painful Pulp in Endodontics-A Review. Rakesh Mittal, Jamal M El- Swiah, Vandana Dahiya; JOHCD, September 2011;5(3) • Pharmacological Strategies to Control Post-operative Endodontic PainZahed Mohammadi, Alireza Farhad, Meisam Khalesi, Dent Res J 2007; 4(2): 61-68 • An update on the antibiotic-based root canal irrigation solutions. Zahed Mohammadi, IEJ Vol 3, No 2 Spring 2008 • Endodontic Consideration for the Usage of Drugs in Pregnant and Lactating Mothers AGGARWAL R, SINGLA M, MITTAL N, Journal of Clinical and Diagnostic Research. 2010 August ;(4):2974-2978 • Antimicrobial agents used in endodontic treatment. Marina George Kudiyirickal, Romana Ivančaková, ACTA MEDICA (Hradec Kralove) 2008;51(1):3–12 • Antibiotics as an intracanal medicament in endodontics: A review Neelam Mittal, Jyoti Jain, indian journal of dentistry 4(2013) 29-34 • Are antibiotics effective for endodontic pain? Ashraf f. Fouad, Endodontic Topics 2002, 3, 52–66
  124. 124. THANK YOU