Intracanal medicaments Nilesh Deshpande JR-II Department of pediatric and preventive dentistry 1

An important objective of endodontic therapy is the removal of necrotic infected pulp and dentinal debris from the root canal system of infected or non-vital teeth. Failure to use an irrigating solution during BMP results in considerable amount of debris to be left behind in the root canal system ultimately leading to endodontic failure. Hence for obtaining an optimum level of disinfection of the root canal system chemo-mechanical preparation is a must. INTRODUCTION 2

HISTORY Prior to 1940’s Water was the most commonly used irrigant as it was: 1.Readily available. 2.Inexpensive. 3.Provided a lubricating effect during instrumentation. 3

 During 1940’s proteolytic enzymes like streptokinase, streptodomase, papain, etc. were being used as irrigating solutions because of their tissue dissolving property.  In 1943, Grossman introduced the concept of using oxidizing agents as irrigants.  In 1945, Daniel formulated an irrigating solution comprising of a amino-acridine.  In 1970’s chelating agents were used increasingly because of their biologically acceptable properties. 4

IDEAL REQUIREMENTS It should be an effective germicide and fungicide. It should be non-irritating to the periapical tissues. It should remain stable in solution. It should have prolonged antimicrobial effect It should be active in the presence of blood, serum and protein derivatives of tissues. It should have low surface tension. It should not interfere with repair of periapical tissues. It should not stain tooth structure It should not induce cell mediated immune response. It should be capable of inactivation in a culture medium. 5

CATEGORIES OF USE That is conditions or situations for which intracanal medicaments have been advocated. Elimination microorganisms. Rendering contents of canal inert Prevention or control of post treatment pain Enhancing Anesthesia Control of persistent periapical abscess 6

CLASSIFICATIONS A.According to DCNA 1.Phenolics - Eugenol - Camphorated monoparachlorophenol (CMCP) - Parachlorophenol (PCP) - Camphorated parachlorophenol (CPC) - Metacresylacetate (Cresatin) - Cresol - Creosote (Beechwood) - Thymol 2.Aldehydes - Formocresol - Glutaraldehyde 3.Halides - Sodium hypochlorite - Iodine - Potassium iodide 4.Steroids 5.Calcium hydroxide 6.Antibiotics 7.Combinations 7

B.According to Grossman 1.Essential oils - Eugenol 2. Phenolic compound - Phenol - Para chlorophenol - Camphorated para chlorophenol - Formocresol - Glutaraldehyde - Cresatin 3.Halogens - sodium hypochlorite - Iodides 4. Quaternary Ammonium compounds - 9-amino acridine 8

INDIVIDUAL INTRACANAL MEDICAMENTS 9

From a biological stand point, sterile normal saline is the best irrigant to use because it causes. I.Least apical tissue irritation or damage. II.Biocompatible. III.Least amount of cell lysis. Physiologic Saline 10

Disadvantages:  Does not remove the smear layer.  Flushes out some of the superficial debris from the root canal system.  Has poor antibacterial properties.  However irrigation followed by ultrasonic and sonic instrumentation have been reported to be almost as effective as 0.5 to 2.5% sodium hypochlorite irrigation in reducing the number of bacteria in infected root canals. 11

Phenol It is the oldest compound for controlling microorganisms. It was introduced by Lord Lister in It is white crystalline substance, and has a characteristic odor derived from coal tar. Phenol is a protoplasmic poison and produces necrosis of soft tissues by its ability to penetrate and disrupt the cell wall of bacteria and subsequently the protoplasm. Liquefied phenol consists of 9 parts of phenol and 1 part water. Highly effective in 1 to 2% concentration. 12

Camphorated Phenol This contains 30% phenol, 60% camphor, 10% ethyl alcohol. It is the least toxic of the phenolic compounds. It has excellent antimicrobial effect and also relieves pain. Camphorating process aims at developing a less caustic medicament as a result of the slow release of phenol. Camphor serves as a vehicle and diluent. 13

Monochlorophenol (MCP) -It is a derivative of phenol and has three isomers of which paramonochlorophenol is the most effective. - Mono chlorophenol is more effective antiseptic and is also more toxic than phenol. 14

Camphorated Paramonochlorophenol (CMPCP) (Developed by Walkhoff 1891) - Contains : 35% monochlorophenol 65% camphor - Its antimicrobial effect is good. - Highly toxic to the tissues. - It is used in the form of vapor forming intracanal medicament. The vapors can pass through the apical foramen. 15

Formocresol Developed by BUCKLEY in 1906 Contents : 19% formaldehyde 35% cresol 46% water Glycerine. or is a combination of formalin and cresol in the proportion of 1:2  Formocresol combines the protein - coagulating effect of phenolic compounds with the alkylating effect of formaldehyde.  The bactericidal effect of formocresol is good at levels as low as 2%. 16

 It is a strong poison and causes widespread destruction of living tissue followed by a persistent inflammatory reaction.  Studies have reported that formocresol treated tissue produced a cell mediated immune response. 17

Glutaraldehyde -It is a colorless slightly soluble in H 2 O. -Slightly acidic -It is a strong disinfectant and fixative -Used in concentration of 2% - Extent of toxicity is less compared to formaldehyde. Its molecular weight is high compared to formaldehyde hence does not penetrate into the periapical tissues. 18

Glutaraldehyde was preferred to formaldehyde:  Irreversible bonding with proteins.  Limited diffusion into tooth structure.  No periapical irritation.  Appears to cause a softening of dentin for limited duration, facilitating the mechanical preparation of the root canal.  Greater reduction in microorganisms with glutaraldehyde 2% can be attributed to the fixative property rendering the microorganisms inert and non- toxic. 19

Cresatin  Also known as metacresylacetate  It is a clear, stable, oily liquid of low volatility.  It has both antiseptic and obtundant properties  Compared to formocresol or camphorated parachlorophenol the antimicrobial effect of cresatin is less 20

Creosote  It is a mixture of phenol and phenol derivatives  Beachwood creosote has long been used in endodontic therapy.  There are several reports on severe tissue irritation and necrosis 21

Alcohols  Ethyl alcohol and Isopropyl alcohol are used.  These denature protiens in high concentration.  Denaturing takes place in presence of water, hence 70% is prefered to 95%  They are not recommended as intracanal medicament 22

Eugenol  It is the chemical essence of oil of clove.  It is related to phenol  It is both an antiseptic and an obtundant  It is slightly more irritating than oil of clove.  Studies have reported that eugenol inhibited intradental nerve impulses  A few reports of allergy to eugenol have been reported. 23

Heavy metal salts  Salts of silver, copper and mercury are used.  They coagulate protiens and act as enzyme inhibitors.  They are toxic.  The mercury salts are rendered less effective by the tissue fluid proteins present in the root canal. Hence they are not often used. 24

N 2 Contains :Paraformaldehyde Phenylmercuric borate Eugenol. Additional ingredients like lead, corticosteroids, antibiotics. - It is claimed to be both intracanal medicament and a sealer - Claims that N 2 has a permanent disinfectant action and unusual antimicrobial properties have been denied by the council on Dental Therapeutics of the American Dental Association. - The antibacterial effect of N 2 is short lived about a week to 10 days. 25

SODIUM HYPOCHLORITE Is one of the most popular irrigating solutions. It has been used as an irrigant for well over 4 decades.  It was first recommended as an antiseptic solution by HENRY DAKIN in 1915 and was called as DAKIN’s SOLUTION during the time of World War-I (NaOCl buffered with sodium bicarbonate).  0.5% NaOCl solution was then used as a treatment for infected wounds. 26

Manufactured: It is made by bubbling chlorine gas through NaOH to form equal amounts of sodium hypochlorite and sodium chloride (NaOH  gas NaOCl + NaCl 2 ) 27

Properties of NaOCl:  Antibacterial action  Strong dissolution property: Fresh tissue Necrotic tissue Fixed tissue  Lubricant – for effective instrumentation.  Bleaching action on discolored teeth.  NaOCl has been used in various concentrations ranging from %.  Most commonly used concentration – 2.5% 28

ACTIONS: Antibacterial: NaOCl exerts its antibacterial action either by: 1.Direct contact with microorganisms. 2.Vapour action. Destruction of the bacteria takes place in two phases: Penetration into the bacterial cell. Chemical combination with the protoplasm of the bacterial cell that destroys it. 29

30  Sodium hypochlorite at 5.25% is an extremely effective antimicrobial agent.  Studies have shown that this solution will destroy most of the microorganisms found in the root-canal system after exposure of 1 minute or less.

FACTORS AFFECTING THE ANTIMICROBIAL PROPERTIES OF NaOCl: Diluting 5.25% NaOCl inhibits its antimicrobial property significantly. Bactericidal effectiveness of 5.25% NaOCl decreases over time. Martin suggested a storage shelf-life of 3 months for undiluted preparations. The antimicrobial property may be achieved in a significantly lesser time by prewarming the solution (room temperature 22°C- body temperature 37°C). 31

32 It maintains a remarkable degree of antimicrobial activity in the presence of organic matter such as blood and serum albumin. ** Briseno (1992) and coworkers demonstrated that the irrigation of the root canal with 1% NaOCl (manual) was more effective against the test organisms (E-edi + S.mutans) than irrigation of the root canal with 2% NaOCl + ultrasound.

TISSUE SOLVENT PROPERTY  NaOCl possesses strong tissue dissolution property for fresh vital tissue, necrotic tissue and fixed tissues. This tissue dissolving capacity equals to that shown by H 2 SO 4 and HCl.  The solvent action of NaOCl has been attributed to its high alkalinity.  The removal of organic tissue by NaOCl is by the release of hypochlorous acid which reacts with insoluble proteins to form soluble polypeptides, aminoacids and other by products. 33

34 NaOCl – hypochlorus acid + insoluble proteins – soluble polypeptides, aminoacids and byproducts. Grossman has shown that it can dissolve an entire pulp in 20 minutes to 2 hours. 5.25% of NaOCl is capable of penetrating into the dentinal tubules and dissolving the contents of the tubules adjacent to the main canal.

NaOCl and Smear layers NaOCl alone is not very effective in removal of the smear layer, but when used in conjunction with other solutions or with ultrasonics it has shown to remove the smear layer effectively. Yamada and associates (2003) reported that a final flushing of 17% EDTA, followed by 10ml of 5.25% NaOCl, was more effective in removing both inorganic and organic debris. These authors concluded, that flushing with a chelating agent removed the final calcific sludge that remained on the canal walls. 35

36  Flushing with 10ml NaOCl removed any remaining organic tissue, thus leaving patent dentinal tubules on the surface of the canal walls.  (Lengiz in 97) showed that the use of 0.5% NaOCl in combination with Ca(OH)2 preparation and ultrasonics in the root canal can effectively remove the smear layer. Also this is considered to be more safer than the use of NaOCl solution is 5% concentration which is proved to be highly toxic.

TOXICITY OF NaOCl TO PERIAPICAL TISSUE Causes: 1.Severe pain. 2.Edema. 3.Profuse haemorrhage both interstitially and through the tooth. This may be followed by (for several days) 1.Increasing edema. 2.Ecchymosis. 3.Tissue necrosis. 4.Parasthesia. 5.Secondary infection (rarely). Majority of cases, have shown complete resolution within a couple of weeks. In some cases they may be long-term parasthesia or scarring. 37

Treatment a)For immediate relief of pain – nerve block and L.A. b)Wet, cold, compress – continually applied to the face – for relief of pain and burning sensation and minimize swelling (for upto 6 hours). c)Analgesics – after emergency treatment. d)To control inflammation – corticosteroids immediately i.v. for 3 days. e)To prevent infection – antibiotics (1wk). Heat packs and warm mouth rinse (after initial treatment). To improve circulation to the area. 38

 Advise the patient concerning the anticipated swelling and ecchymosis.  Give the patient both verbal and written instructions.  Reassure the patient that he will regain his normal appearance within a short period. 39

HYDROGEN PEROXIDE 3% H 2 O 2 was recommended as a canal irrigant because of: a)Its effervescent action. b)Disinfecting properties. 40

 Effervescent action was specially indicated in mandibular teeth where the bubbling of the peroxide was thought to lift debris from the canal system almost defying gravity.  H 2 O 2 does not possess tissue dissolution properties Not effective as a lubricant.  Hence, alternate use of H 2 O 2 + NaOCl irrigating solutions was recommended by Grossman. 41

42 This alternate irrigation regimen during Chemo-mechanical preparation produces: a)Transient but energetic effervescence that mechanically forces out debris and microorganisms out of the canal. b)At the same time the O2 that is liberated in an active state assists in destroying the anaerobic microorganisms. c)The permeability of dentinal tubules is increased allowing deeper penetration of intracanal medicament. d)Increases the bleaching action on discolored teeth.

CHELATING AGENTS  Aid in the mechanical enlargement of difficult root canals by softening the root canal dentin walls.  EDTA – Ethylene diamine tetra-acetic acid composed by Disodium salt of EDTA distilled water 100ml, 5N NaOH 4.25ml.  This was 1 st described for use in endodontics by Ostby. 43

Functions a)It has certain dentin dissolving effects desirable in all kinds of root canal therapy – ease in instrumentation. b)It reduced the time necessary for debridement and disinfection. c)It aided in enlarging narrow / obstructed canals. d)It helped make possible the bypassing of broken instruments in the canals. e)Removed the inorganic component of smear layer. f)Had no corrosive effects on the instruments. 44

Action The sodium salts of EDTA are capable of forming soluble non-ionic chelates with large number of metallic ions viz. calcium ions. Because EDTA would seek the calcium metal ion in the hydroxyapatite crystals of dentin in a chelate and thereby act to demineralize dentin and enamel. Ostby and associates found that EDTA decalcified dentin to a depth of 20-30µm in 5 minutes. Franklin et al in 2004 reported that it is possible to overchelate a canal which can lead to perforation. 45

 EDTA is known to remain active within the canal for 5 days.  If not inactivated the solution may seep into the periapical tissues and damage the bone.  Therefore at the completion of appointment, the canal must be irrigated with NaOCl. 46

RC Preparation It’s a combination of 17% EDTA + urea peroxide 10%, developed by Stewart and colleagues. Effective lubricating and cleaning agent. 1.It allows deeper penetration of the medicament into the dentin. 2.It is not water-soluble. 3.It is popularly used in combination with NaOCl. 4.Because it is thought to produce a bubbling action helps loosen and float out dentinal debris. 47

48 Studies have shown RC preparation might affect the apical seal. Cook and associates in 1998 reported twice as much leakage in canals obturated with GP or silver cones following cleaning and shaping with RC preparation NaOCl than with NaOCl alone.

EDTA-c (commercial name) Quaternary ammonium compound to EDTA + Cetavlon which has greater germicidal acitivity and disinfecting properties. REDTA – A quaternary ammonium bromide + EDTA solution. To reduce the surface tension + increase the permeability of the solution. 49

SALVIZOL Another chelating agent is salvizol based on aminoquinaldinum diacetate. Properties: It has surface acting property similar to quaternary ammonium groups. Chelating action. Organic debridement. Bactericidal activity. 50

ORGANIC ACIDS The use of organic acid irrigants to irrigate and debride root canals is as old as root canal therapy itself. CITRIC ACID: Has been recommended as a canal irrigant because of its ability to demineralize and remove the smear layer effectively. 2 observations were made: It acts as a chelating agent on dentine. Therefore, it occurs naturally in the body, it is more acceptable biologically than other acids ((Jenkin and Dawer 1963). 51

The chelating action of citric acid softens the dentin and facilitates easy removal of the smear layer. CA has been used effectively in concentration of 10, 25 and 50% as RC irrigant. Disadvantages: C.A. may leave precipitated crystals (calcium and phosphate containing crystals) in the canal wall. Which may be a disadvantage. 1.Citric acid has been used in combination with NaOCl to effectively clean the R.C. 2.C.A. removes smear layer better than many acids like poly acrylic acid, lactic acid and phosphoric acid. 52

TANNIC ACID Tannic acid is another cleansing agent for root canal preparation was suggested by Graham Mount. It has been extensively used in the treatment of burns (more than 100 years old). Action: It acts as a surface coagulant by precipitating proteins. *Studies have shown that the use of tannic acid in the root canal as an irrigant cleansed the canal more effectively than the conventional combination of NaOCl + H2O2. 53

CHLORHEXIDINE GLUCONATE Chlorhexidine has become recognized as an effective antimicrobial agent and its use as a potential endodontic irrigant has been demonstrated in the last decade. Recently, it has been accepted as a root canal irrigant in endodontics. Advantages: Has a broad spectrum antimicrobial action. Relative absence of toxicity. Disadvantage – it is not known to possess a tissue dissolving property. 54

Structure is a symmetrical cationic molecule consisting of: 4-chlorophenyl rings and 2 biguanide groups Connected by a central hexamethylene chain Specturm of activity Chlorhexidine is bactericidal and effective against gram +ve, gram-ve, yeast, Candida albicans. 55

56 Action: Acts by adsorbing into the cell wall of the microorganisms and causing leakage of the intracellular components. At low concentration has bacteriostatic effect. At higher concentration, chlorhexidine is bactericidal because of precipitation or coagulation of the cytoplasm caused by protein cross linking. The bacteriostatic effect of chlorhexidine is considered to be more effective. The bound chlorhexidine molecule is slowly released for upto 24 hours, as the concentration decrease.

According to Klimn et al When used as an intra canal irrigant in the endodontic treatment for periapical lesions: Clinical relief of symptoms. Sterility. Reduction in the size of periapical lesions. All at a mean follow up of 24 months. In another study (O hara et al) showed that chlorhexidine was the most efficient antibacterial agent when compared to 3% H2O2, 5.25% NaOCl, saline REDTA 17%. 57

Iodides : - Iodine has been used for many years and is known for its mild effect on living tissue. - Iodine is highly reactive, combining with proteins in a loosely bound manner so its penetration is not impeded. - Iodine potassium iodide which contains 2% I 2, 4% KI and 94% distilled water has excellent antimicrobial activity and minimal toxicity and tissue irritating qualities. 58

Cationic detergents - The quaternary ammonium compounds have low surface tension and good cleansing effect. - The antimicrobial effect of these compounds are not strong. - Mechanism of action is as follows, the ‘Quats’ are positevely charged and the microorganisms are negatively charged. Thus a surface active effect results in which the compound clings to the microorganism and reverses the charge. - These compounds may delay wound healing - These compounds are used in the concentrations between 0.1 to 1% for root canal irrigation, but rarely as intracanal dressings - Salvizol is also a detergent suggested for irrigation during root canal instrumentation - It has chelating effect - Salvizol causes some degree of tissue irritation 59

9-AMINOACRIDINE The efficacy of 9-aminoacridine has been reviewed by Schmitz. Properties: 1.Antibacterial action. 2.Low toxicity. 3.Osteogenic potential. Disadvantage: Not a chelator. Not a tissue solvent. It use is not widespread. 60

Mechanism of action: Disruption of cellular metabolic pathways of microorganisms: -Inhibition of cells, protein synthesis. -Inhibition of DNA synthesis. Use: a)Management of endodontically involved teeth with large periapical abscess. b)Recommended as pressure irrigation of the periapical tissues via the canals. c)The drug may be sealed in the canal as an interim medication ( low inflammatory potential) 61

Glyoxide Glyoxide is an irrigation solution i.e. comprised of 10% urea peroxide (Carbamide peroxide) in a vehicle of anhydrous glycerol. Use: Narrow and curved canals where slippery effect of glycerol is maximized for instrumentation. 62

Action: a)Antibacterial activity that is more potent than 3% H 2 O 2. b)Enhances root canal lubrication without softening the dentin. (less chance of root perforation) a)It is less toxic to periapical tissues than NaOCl. b)It also has greater solvent action than 3% H 2 O 2. 63

DOXYCYCLINE HYDROCHLORIDE A hydroxy derivative of tetracycline. It is the most potent anticollagenase antibiotic among commercially available tetracyclines. Advantages: a)The dentin surface is capable of acting as a reservoir by adsorbing and slowly releasing antibacterial levels of doxycycline into the adjacent environment for several days following topical applications of this antibiotic solutions. b)Inhibit extracellular collagenase activity and bone resorption. 64

Metronidazole  Antibiotic spectrum confined solely to obligate anaerobes.  Active against bacteroides, porphyromonas fusibacterium, clostridium and peptococci and peptostreptococci. Barnett and Tronstad in 2002 reported the successful use of metranidazole in controlling infections by bacterioides spp and pseudomonas spp colonized at root ends of endodontically treated teeth that had failed to heal and remained refractory to all other treatment. 65

66 Adverse reactions: 1.Nausea. 2.Headache. 3.Metallic taste. 4.Xerostomia.

Calcium hydroxide  Hermann introduced Ca(OH) 2 paste as an intra canal medicament in  Thick suspension of Ca(OH) 2 powder in sterile water or saline.  The high pH of calcium hydroxide paste is responsible for the destructive effect on bacterial cell membranes and protein structures.  Aid directly or indirectly in the dissolution of necrotic pulp tissue. Tissue submerged in Ca(OH) 2 for a day is more easily dissolved with NaOCl than is untreated tissue. Bystrom et al showed that Ca(OH)2 paste effectively eliminated all microorganisms in infected root canals when the dressing was maintained for 4 weeks. 67

68 Mode of application :  The paste is introduced into the root canal with a lentulo spiral, dried with coarse absorbent points and packed with appropriately sized root canal pluggers.  Temporary cement is then placed for an effective seal.

Antibiotics  Antibiotics are indicated in a small minority of cases when root canal infection persists despite other antiseptics.  Ladermix paste or polyantibiotic paste (PBSC) are used 69

Ledermix paste 1% triamcinelone acetonide (Glucocorticosteroid) 3% dimethl chlortetracycline PBSC paste Potassium penicillin G (10,00,000 units) Bacitracin (10,000 units) Streptomycin paste (1gm) Sodium caprylate / Nystatin (1gm) 70

Conclusion  Debridement of the root canal systems is essential for a predictably successful endodontic treatment.  The identification and elimination of bacteria, removed of other necrotic products from the canal with appropriate irrigating solutions with proper technique ensures definite fulfillment of one of the objectives of root canal therapy. 71