Intracanal medicaments

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intracanal medicaments


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INTRACANAL MEDICAMENTS DR. AKANKSHA GAONKAR Department of conservative dentistry and endodontics Maratha Mandal dental college, Belagavi

CONTENTS Introduction History Definition Rationale Ideal requirements of an Intracanal medicament Objectives Indications of Intracanal medicaments Classification of Intracanal medicaments -Grossman - Franklin Weine - DCNA Intra canal medicaments - Essential oils

- Aldehydes - Halogens - Calcium hydroxide - Chlorhexidine - Sulfonamides - Antibiotics - Corticosteroid antibiotic combination - Herbal medicaments Recent advancements Application of intracanal medicaments Frequency of medication Root canal microflora Conclusion References - Phenolic compounds

INTRODUCTION Disinfection of pulp space is an important step during and after cleaning and shaping. It primarily involves cleaning and shaping the root canal space with endodontic instruments along with irrigants . However, in certain clinical conditions, the polymicrobial nature of the endodontic infection demands the use of an intracanal medicament in addition to the irrigants . Intracanal medicaments are used for root canal disinfection as part of controlled asepsis in an infected root canal and their role is secondary to shaping and cleaning of the root canal.

HISTORY The historical origins of intracanal medicaments date back to very early times. Beechwood creosote was mentioned in the 1840 article Creosote and Cotton in Fang Filling. In 1884 , Richmond recommended applying a small-sized piece of orangewood with phenol in order to devitalise the pulp. Thus, phenolics, which include eugenol (this may be differentially classified as an essential oil), parachlorophenol , camphorated parachlorophenol , camphorated monoparachlorophenol , cresatin ( metacresylacetate ), cresol, thymol and creosote, are drugs with a long history in the dental field that begins in the 1800s .

Many combinations of these drugs were prepared and played major roles in root canal treatment from the 19th to the 20th century . Formocresol , which is categorised into the aldehydes, was often used as a root canal medicament and played a major role in root canal treatment since Buckley referred to it as an effective intracanal medicament in 1904 .

DEFINITION A chemical agent sealed within the root canal system; used between appointments as an anodyne and/or antimicrobial agent. ( American Association of Endodontists) “ Temporary placement of medicaments with good biocompatibility into root canals for the purpose of inhibiting coronal invasion of bacteria from the oral cavity”. International Dental Journal (2009) Vol. 59/No.1

RATIONALE The main rational behind intracanal medicament is to kill the bacteria inside the root canal and to avert reinfection. Furthermore, anaerobic bacteria may invade the dentinal tubules of the canals with necrotic pulps. The medicament should inhibit microbial re-colonization of the cleaned parts of the root canal system by preventing Residual microorganisms from growing New microorganisms invading

Why use medicaments? Australian Dental Journal 1990;35:5.

Requirements of an Ideal Root Canal Medicament: (GROSSMAN)

OBJECTIVES 1. Destruction of micro-organisms: The main objective is to kill all viable microorganisms or to disinfect all pathogens in the canal space. 2. Rendering contents of canal inert: It notifies the activities by using chemicals which “mummify” fix or otherwise deactivate the tissue or debris remains in the pulp space. If this process is applied successfully, it can deactivate those residual bacteria remains in pulp space. 3. Prevention or control of post-treatment pain: The main indication is to lessen or alter the inflammatory effect. Medicament will execute this with its antimicrobial action or by pharmacologically altering the inflammatory effect.

4. Enhancing Anesthesia: In the condition when pulp is difficult to anesthetize, suitable agents can be administered to reduce the sensitivity of the inflamed pulp. The pulp could be removed during appointments with less anesthetic difficulty. 5. Control of persistent periapical abscess: The sign of an active periapical inflammatory lesion can be identified by significant pain in canal or swelling after treatment or recurrently “weeping” canal. To subside this difficult situation, intra canal medicaments have been suggested.

Chong and Pittford’s Indications of Intracanal Medicaments:

CLASSIFICATION

Phenol and related compounds eugenol camphorated paramonochlorophenol metacresylactate cresol thymol PBSC penicillin bacitracin streptomycin caprylate Sulphonamides Corticosteroid- antibiotic combinations Calcium hydroxide According to Franklin S Weine

ESSENTIAL OILS It has been used in endodontics for many years. This substance is the chemical essence of oil of clove and is related to phenol. Effects of eugenol are dependent on tissue concentrations of the eugenol. Eugenol

Uses of eugenol • Used as an intracanal medicament. • Used as a root canal sealers. • Part of temporary sealing agents.

PHENOLIC COMPOUNDS It is one of the oldest antimicrobial agents used in medicine , introduced by Lord Lister into medicine in 1867. It was used for many years for its disinfectant and caustic action. However, it has strong inflammatory potential , so, at present, it is rarely used as an intracanal medicament. PHENOL

Liquefied phenol (Carbolic acid) consists of 9 parts of phenol and 1 part of water. It is a nonspecific protoplasm poison that has an optimal antibacterial effect at 1% to 2%. Many dental preparations use much too high a concentration of phenol (e.g., in the range of 30%). At such a concentration, the antimicrobial effect in vivo is lower than optimal and of very short duration. Phenolic compounds are often available as camphorated solutions. Camphoration results in a less toxic phenolic compound because it slows the release of toxins to the surrounding tissues.

It has been a very popular component of dressing as phenol is no longer used in endodontics because of its high toxicity to efficacy ratio. Composition • This is substitution product of phenol in which chlorine replaces one of the hydrogen atoms (C6H4OHCl). • On trituration with gum camphor, these products combine to form an oily liquid. Concentration: 1% aqueous solution is preferred. Uses: Used as a dressing of choice for infected tooth. PARACHLOROPHENOL

The camphor present in camphorated parachlorophenol reduces irritating effect of pure parachlorophenol and acting as a diluent and vehicle . Grossman brought to light the antimicrobial effect of camphorated parachlorphenol compared to some other root canal medicaments. CAMPHORATED PARACHLOROPHENOL

Composition 2 parts of parachlorophenol + 3 parts gum camphor Camphorated monochlorophenol (CMCP) CAMPHORATED MONOPARACHLOROPHENOL (CMCP)

It is acquired from coal tar with or without containing a trace of phenol having properties like Ortho, Meta and Para-isomeric cresol. It is colourless or pinkish liquid in nature. Cresol (C6H4OHCH3) can substitute phenol considering its 3-times more powerful disinfectant capacity. CRESOL(TRICRESOL)

As reported by Schilder and Amsterdam, Cresatin possesses the same desirable qualities and actions as that of CMCP, yet even less irritating to periapical tissues. Composition: This substance is clear, stable, oily liquid of low volatile nature known as metacresyl acetate . CRESATIN

It is a compound of cresatin , P-chlorophenol and camphor in 1:1:2 ratio. It is found more effective than cresatin as an antiseptic and less irritating than chlorophenol. CRESANOL

ALDEHYDES Formaldehyde , paraformaldehyde and glutaraldehyde are commonly used intracanal medicaments in root canal therapy. These are water-soluble protein denaturing agents and are considered among the most potent disinfectants. All formaldehyde preparations are potent toxins with an antimicrobial effectiveness much lower than their toxicity.

Formocresol contains formaldehyde as its main ingredient and is still widely used medicament for pulpotomy procedures in primary teeth but its toxic and mutagenic properties are of concern. Composition of formocresol •  Formaldehyde — 19% •  Cresol — 35% •  Water and glycerine — 46% FORMOCRESOL

• It is polymeric form of formaldehyde and is commonly found as component of some root canal obturating material like endomethasone . • It slowly decomposes to give out formocresol , its monomer. • Its properties are similar to formaldehyde that is toxic, allergenic and genotoxic in nature. PARAFORMALDEHYDE

It is used as intracanal medicament and as a sealer containing paraformaldehyde and phenyl mercuric borate as demonstrated by Sargenti and Richter. The properties present in N 2 have permanent disinfectant action and unusual antiseptic agent that are irritating and toxic with high degree of antimicrobial activity. It has been observed that the antibacterial effect of N 2 is of short duration and degenerate in about 7 to 10 days . N 2

HALOGENS Disinfectant action of the halogens is related its atomic weight and its action is inversely proportional. Chlorine is having greatest disinfectant action among the members of this group also having lowest atomic weight. Sodium hypochlorite and Chloramines are the source of active chlorine which is used for short term dressing of the root canal .

Chlorine compound has excellent antimicrobial properties. It is a chlorine compound with a good antimicrobial action. It is used in the concentration of 5%. It remains stable for a long-period of time. It can be used to disinfect gutta-percha points, and can be used in patients allergic to iodine. CHLORINE CHLORAMINE-T

Iodine in the form of Iodine potassium iodide ( IKI), is a very effective antiseptic solution with low tissue toxicity. IKI is an effective disinfectant for infected dentin and can kill bacteria in infected dentin in 5 minutes in vitro. IKI releases vapors with a strong antimicrobial effect. The solution can be prepared by mixing 2 g of iodine in 4 g of potassium iodide; this mixture then is dissolved in 94 ml of distilled water. IODINE

CALCIUM HYDROXIDE Hermann introduced the use of Ca(OH) 2 in endodontics in 1920. It is a crystal that is poorly soluble in water and only induces localised effects. The bactericidal effects are caused by its high pH (12.5-12.8), which prevents the growth and survival of bacteria, most of which cannot survive pH 11 or above.

Mechanism of Action: Calcium hydroxide has antibacterial properties and has the ability to induce repair and stimulate hard-tissue formation. The bactericidal effect is conferred by its highly alkaline pH . The release of hydroxyl ions in an aqueous environment is related to the antimicrobial property. Hydroxyl ions are highly oxidizing free radicals that destroy bacteria by:

Ca(OH) 2 is a slow-acting antiseptic.

In addition to killing bacteria, Ca(OH) 2 has the extraordinary ability to hydrolyze the lipid moiety of bacterial lipopolysaccharides (LPS), thereby inactivating the biologic activity of the lipopolysaccharide and reducing its effect. This is a very desirable effect because dead cell wall material remains after the bacteria have been killed and can continue to stimulate inflammatory responses in the periradicular tissue.

Calcium hydroxide is reported to be effective in controlling the inflammatory exudates from the periapical region, and the mechanism behind this action may be related to its antimicrobial properties, contraction of capillaries, and formation of an apical plug .

Vehicles: The vehicle used to mix Ca(OH) 2 and the manner in which it is dispensed has a significant role to play in achieving maximum antibacterial effects as an intracanal medicament in endodontics. According to Fava and Saunders, the vehicles can be classified as follows: Aqueous—e.g. sterile water, normal saline Viscous— glycerine , polyethylene glycol, and propylene glycol. The other medicaments combined with Ca(OH) 2 in order to achieve synergistic antimicrobial effect include CMCP and 0.12% chlorhexidine.

Commercially, calcium hydroxide for intracanal disinfection is available as a non-settable form which can be removed with minimum instrumentation. The mixture should be thick to carry as many Ca(OH) 2 particles as possible. This slurry is best applied with a Lentulo spiral . For maximum effectiveness, the root canal must be filled homogeneously till the working length. Because calcium hydroxide does not vaporise , it must be placed in tight contact with the root canal walls because its effectiveness depends on the degree of contact with the walls as well as its antibacterial activity. PLACEMENT

The aim of this study was to investigate in vitro the antimicrobial activity of calcium hydroxide in combination with several vehicles against some microorganisms commonly isolated from root canals. It was concluded that diffusion and antimicrobial activity of calcium hydroxide were affected by the type of vehicle used.

Limitations of Calcium Hydroxide The handling and proper placement of Ca(OH) 2 present a challenge to the average clinician. Also, the removal of Ca(OH) 2 is frequently incomplete, resulting in a residue covering 20% to 45% of the canal wall surfaces, even after copious irrigation with saline, NaOCl , or EDTA. Residual Ca(OH) 2 can shorten the setting time of zinc oxide eugenol–based endodontic sealers. Most notably, it may interfere with the seal of the root filling and compromise the quality of treatment.

An additional concern is that Ca(OH) 2 is not totally effective against several endodontic pathogens, including E. faecalis and Candida albicans. Recently the ability of Ca(OH) 2 to completely eradicate bacteria from the root canal has been questioned. In vitro studies have shown that dentin can inactivate the antibacterial activity of Ca(OH) 2 Other studies have also indicated that Ca(OH) 2 could not predictably eliminate bacteria or that cultures changed from negative to positive after Ca(OH) 2 placement.

S ome studies have supported the antimicrobial effect of Ca(OH) 2 , others have questioned its efficacy. The antimicrobial effect of Ca(OH) 2  is related to the hydroxyl ions released in an aqueous environment, which affects cytoplasmic membranes, proteins, and the DNA of microorganisms. Ca(OH) 2  has a wide range of antimicrobial effects against common endodontic pathogens, but it is less effective against specific species such as  E. faecalis   or  C. albicans . The addition of vehicles or other agents might contribute to the antimicrobial effect of Ca(OH) 2 . Although it remains controversial, it seems that by mixing Ca(OH) 2  with CHX, the antimicrobial activity of Ca(OH) 2  can be increased.

CHX in liquid, gel, or in a controlled-release device has been suggested as an alternative intracanal medication to replace Ca(OH) 2 . Chlorhexidine exhibits substantivity , broadspectrum activity and low toxicity , these properties make it well suited for irrigation and dressing applications in endodontics. CHLORHEXIDINE(CHX)

As a medicament, it can be used as: 2% CHX gel Mixture of CHX and Ca(OH) 2 CHX has been shown to be effective against both E. faecalis and Candida albicans.

As suggested, Chlorhexidine may be a useful adjunct in the treatment of inflammatory root resorption which can reduce the inflammatory resorption significantly compared to non-medicated teeth. Jose F Siqueira et al had conducted a study on the elimination of candida albicans infection of the radicular dentin by applying Chlorhexidine mixed with zinc oxide which observed highly effective in killing candida albicans within dentin.

SULFONAMIDES Sulfanilamide and Sulfathiazole are used as medicaments by mixing with distilled water or by placing a moistened paper point into a fluffed jar containing the powder. Yellowish tooth discoloration has been reported after use. Sulfonamides are usually recommended while giving closed dressing in a tooth which had been left open after an acute periapical abscess.

ANTIBIOTICS AS MEDICAMENTS

POLY ANTIBIOTIC PASTE ( PBSC ) - by Grossman(1951) Penicillin (1,000,000 units of potassium penicillin G)- effective against gram positive microorganism. Bacitracin (10,000 units)- effective against penicillin resistant microorganisms. Streptomycin (1gm)- effective against gram negative microorganisms. Caprylate (1gm)- sodium salt, effective against fungi.

PBSN: Penicillin —effective against gram-positive microorganisms Bacitracin —effective against penicillin-resistant microorganisms Streptomycin —effective against the gram-negative microorganisms Nystatin —effective against fungi. Both are available in a paste form that may be injected into root canals or impregnated on paper points . Because there is no volatility, the drug must be placed in the canal to have effect in that area.

TRIPLE ANTIBIOTIC PASTE The triple-antibiotics regimen, composed of metronidazole , ciprofloxacin , and minocycline , was first tested for its effectiveness against Escherichia coli–infected dentin in vitro. The same research group also tested its bactericidal efficacy against microbes from carious dentin and infected pulp. They found that the mixture of antibiotics is sufficiently potent to eradicate the bacteria .

Triple antibiotic powder, either mixed with normal saline or 2% chlorhexidine , produced the largest zone of inhibition against E. faecalis . The triple antibiotic paste is very effective against E. faecalis . Concentrations used: 1:1:1 - Hoshino et al ,1996 1:3:3- Takushige T et al, 2004

One potential concern of using an intracanal antibiotic paste is that it may cause bacterial resistance . Intracanal use of minocycline can cause tooth discoloration , creating potential cosmetic complications.

INDICATIONS FOR ANTIBIOTIC PASTES

CORTICOSTERIODS- ANTIBIOTICS COMBINATIONS Highly effective in the treatment of over instrumentation . Placed in the inflamed tissue by a paper point or reamer to be effective. The steroid constituent reduces the periapical inflammation and gives instant relief of pain.

SEPTOMIXINE FORTE & PULPOMIXINE Septomixine Forte and Pulpomixine both contain the corticosteroid dexamethasone (0.05 per cent and 1.0 per cent, respectively) as the anti-inflammatory component. While dexamethasone is an effective anti-inflammatory agent, other corticosteroid agents such as triamcinolone are known to be more potent in their local reaction and with less systemic side effects .

LEDERMIX Schroeder developed the material that is now commercially marketed as Ledermix paste. Ledermix paste is a glucocorticosteroid -antibiotic compound.

Ledermix paste placed in the root canal has been shown to be capable of diffusing through the dentinal tubules and cementum to reach the periodontal and periapical tissues. It can be used in all cases involving inflammation and/or infection associated with the root canal system and periapical tissues, even if the apical foramen is blocked or closed .

The placement of Ledermix paste in the root canal space has been reported to add to the efficacy of the treatment of periapical infection and has been reported to reduce the incidence of pain following initial canal debridement. Ledermix paste is a non-setting , water-soluble paste material for use as root canal medicament or a direct or indirect pulp capping agent.

Ledermix paste has also been shown histologically to eliminate experimentally induced external inflammatory root resorption in vivo. A study also reported that Ledermix paste had no damaging effects upon the periodontal membrane and that this paste was an effective medication for the treatment of progressive root resorption in traumatically injured teeth.

COMBINING MEDICAMENTS Several reports have discussed the effect of combining Ledermix paste with calcium hydroxide in a 50:50 mixture. A higher success rate was reported over conventional calcium hydroxide therapy, especially in producing calcified bridging and in preventing an acute exacerbation of an already existing inflammation.

Combining Ledermix paste with Pulpdent paste in a 50:50 mixture as a root canal dressing has been investigated.

HERBAL MEDICAMENTS

Considering the ineffectiveness , potential side effects and safety concerns of synthetic drugs, the herbal alternatives for endodontic usage might prove to be advantageous.

Propolis Propolis is prepared from resin collected by bees from trees of poplars, conifers and flowers of genera clusia . Propolis is a good antimicrobial and anti- inflammatory agent, and therefor can serve as a good intracanal irrigant and intracanal medicament. Propolis can be used as short-term intracanal medication in cases of pulp and periapical inflammatory processes.

Curcumin Curcumin which is the main yellow bioactive component of turmeric has been shown to have a wide spectrum of biological actions, including antimicrobial , anti-inflammatory and anti- oxidant activities.

A study showed that there was a gradual decrease in the anti-bacterial activity of curcumin at 3 and 7 days which may be due to the buffering ability of dentin. Curcumin does not affect the micro hardness of root dentin and is a potential intracanal medicament. AR Prabhakar et al. 2013 Pulpotomy treatment using turmeric powder in primary teeth has shown good clinical and radiographic success. Purohit R et al, 2017

Arctium Lappa This plant is popular all over the world for its therapeutic applications. It is found to have antimicrobial action against microorganisms causing endodontic infections. It is a potential intracanal medicament.

Nissin Nissin is a naturally occurring antimicrobial peptide, produced by Streptococcus lactis sub species lactis. It has antimicrobial activity against a wide range of bacteria and their spores. The few experiments which have been done using nisin have shown that it can kill all the bacteria effectively in the canal and the results were comparable to calcium hydroxide. Turner et al, 2004

Mode of action: Not completely understood but is likely that it interacts with phospholipid membrane of the target bacterial cell . It disrupts the cellular membrane inducing leakage of small intracellular contents from the cell. The delivery mechanism of Nisin is by dissolving it in sterile water.

RECENT ADVANCEMENTS

MEDICATED GUTTA-PERCHA New gutta-percha points containing Ca(OH) 2 in a 50% to 51% concentration in place of zinc oxide is available in the market which makes easier placement and removal of Ca(OH) 2 .

BIOACTIVE GLASS Research is underway in the use of bioactive glass as an intracanal medicament. Some new obturating materials (e.g., Resilon [ Pentron Clinical Technologies, Wallingford, CT]) contain bioactive glass.

In one study, the glass used was composed of 53% SiO 2 (w/w), 23% Na 2 O, 20% CaO , and 4% P 2 O 5 and was prepared from reagent-grade Na 2 CO 3 , CaHPO 4 , 2H 2 O, CaCO 3 , and Belgian sand. When used in root canals, bioactive glass was found to kill bacteria, but the mechanism of action was not pH related, and dentin did not seem to alter its effect.

ODONTOPASTE It is a zinc oxide-based root canal paste with 5% clindamycin hydrochloride and 1% triamcinolone acetonide . Clindamycin is effective against many endodontic pathogen including Streptococci,  Peptostreptococcus , Actinomyces, Fusobacterium, Eubacterium,  Propionobacterium , Microaerophilic,  Peptococcus ,  Porphyromonas ,  Veillonella  and  Prevotella . Clindamycin paste as an intracanal dressing has good antibacterial effect. This antibiotic provides a bacteriostatic activity, and acts as interim dressing material preventing bacterial repopulation within the root canal. T he steroid part , triamcinolone acetonide, can temporarily reduce inflammation and postoperative pain .

APPLICATION OF INTRACANAL MEDICAMENT

Mode of application is an important aspect in the selection of an intracanal medicament. Two methods are basically followed for placement. The medicament can be placed in the pulp chamber by placing it on a cotton pellet Prepared medicament can be flooded in the root canal(injection technique).

Pulp chamber is thoroughly dried up with sterile cotton pellets and paper points. Bottle containing medicament is inverted to allow the liquid to cling to the side near the mouth of the bottle. The sterile cotton pellet is lightly wiped on the inside, picking up some of the liquid. The cotton pellet is then squeezed in a sterile gauze sponge. The amount of medicament remaining in the pellet is more than sufficient to render its temporary antibacterial action.

5. The medicated pellet is placed only in the pulp chamber. The pulp chamber is sealed to prevent recontamination from marginal leakage or actual loss of seal before the next appointment. A fast setting temporary cement (zinc oxide eugenol based) gives a seal superior to other materials. A thickness of 3-5mm is necessary to ensure an effective seal.

INJECTION TECHNIQUE

Most respondents (48.8%) were in the habit of using injecting syringes to insert paste-based ICMs, significantly outweighing the lentulo spiral users (23.8%) ( p =0.009), with no significant differences between GDPs and endodontists ( p =0.386)

Antiseptic or disinfectant dressings should preferably be changed after a week and not longer than two weeks. because it will be diluted by the periapical exudates and decomposes by the interaction with the bacteria in the root canal. Frequency of medication?

R oot canal microflora

Anaerobes: Gram positive cocci – Peptostreptococcus Gram positive bacilli - Lactobacilli, Propionibacterium , Actinomyces & Eubacterium Gram negative cocci - Veillonella parvula Gram negative bacilli -Bacteroides & Fusobacterium Aerobes: Streptococci Staphylococcus Diptheroids

  Aim :   The aim is to determine the difference in antibacterial effectiveness between a combination of calcium hydroxide with 2% CHX digluconate or 25% propolis as an intracanal medicament against  E. faecalis (in vitro)  bacteria.  Conclusion:   The combination of calcium hydroxide with propolis 25% more effective than the mixture of calcium hydroxide with 2% CHX digluconate as root canal medicament against  E. faecalis  bacteria.

Aim:   To evaluate and compare the effect of antibacterial intracanal medicaments on inter-appointment flare-up in diabetic patients. Conclusions:   Calcium hydroxide and triple antibiotic paste are effective for managing inter-appointment flare-ups in diabetic patients. Triple antibiotic paste is more effective than calcium hydroxide in preventing the occurrence of flare-up in diabetic patients.

Aim: To compare the antimicrobial effect of Calcium hydroxide paste ( CaOH ), Chlorhexidine gluconate (CHX) gel and AntibioticCorticosteroid paste against Streptococcus mutans , Enterococcus faecalis and Candida albicans in root canal lumen and radicular dentin. Conclusion: CHX was the best medication used to eliminate the different tested organisms at the two experimental sites. S. mutans was the most sensitive microorganism to the whole tested medications, while C. albicans was the most resistant one.

Usage of intra-canal medications (ICMs) in different scenarios of non-vital cases

CONCLUSION The uses of intracanal medicaments in endodontics have number of reason considering its ill effects such as mutagenic, carcinogenic and periradicular tissue irritation. The treatment aspect of this medicaments has been improved to certain extent by culture tests taking into account of the sensitivity of the drugs to certain groups of bacteria but not its by-product.

From the start of extirpation of the pulp to the obturation, disinfection process is followed continuously applying intracanal medicaments to disinfect the canal, make it inert, dry, reduce postoperative pain and prevent re-infection. In present day dental practice, intracanal medicaments are being applied in certain conditions for gaining utmost success of root canal treatment.

REFERENCES Grossman's Endodontic Practice-13 th edition Arnaldo Castellucci vol 1 Wein’s Endodontic Therapy – 5 th edition Vimal K Sikri- Essentials of endodontics- 2 nd edition Application of Intracanal Medicaments: A Review Himadri pal, Arpita sarkar , Lopamoodra das, Subrata saha , Subir Sarkar Medicaments: Aids to success in endodontics. Part 1 A review of the literature Paul V. Abbott, BDSc (WA), MDS(Adel), FRACDS(Endo)- Australian Dental Journal 1990.

Antimicrobial effect of different intracanal medications on various microorganisms D.A. Attia, A.M. Farag, I.K. Afifi, A.M. Darrag - D.A. Attia et al. / Tanta Dental Journal 12 (2015) Root canal medicaments-Nobuyuki Kawashima, Reiko Wadachi and Hideaki Suda Tokyo, Japan Thai Yeng and Peter Parashos Melbourne, Australia-International Dental Journal (2009) Vol. 59/No.1
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