New Developments in Intracanal Medicaments: A Critical Apprisal

INTRODUCTION

Currently, one of the concerns in Endodontics is the treatment of teeth with necrotic pulps and periapical pathosis because post-treatment disease persists more often than in cases without periapical disease^1,2 .In teeth with chronic periapical lesions, there is a greater prevalence of gram-negative anaerobic bacteria disseminated throughout the root canal system,(dentinal tubules, apical resorptive defects and cementum lacunae),including bacterial biofilm.^1,2,3,4 .Because these areas are not reached by instrumentation, the use of a root canal medicament is recommended to aid in the elimination of these bacteria and thus increase the potential for clinical success .Teeth with and without radiographic evidence of of periapical disease could be considered as different pathological entities requiring different treatment regimens. Where bone loss has occurred, the use of a root canal medicament between treatment sessions is recommended, because the success of treatment in periapical pathosis is directly related to the elimination of bacteria, products and sub-products from the root canal system. The procedures and medicaments used in root canal treatment should not only lead to bacterial death, but also to the inactivation of bacterial endotoxin.⁵ Micro organisms play a major role in the development and progression of pulp and periapical diseases. Bacteria may present in the root canals or in the dentinal tubules, accessory canals, canal ramifications, apical deltas, fins and transverse anastomoses.The combination of mechanical instrumentation and irrigating solutions will render 50-70%of infected free of micro organisms⁶. Since there is no entirely predicable way, in one treatment session in infected root canals, to ensure complete elimination of root canal bacteria, an effective intracanal medicament in root canal is required for a predetermined time period to predictably eradicate or destroy any remaining bacteria. Therefore anti microbial agents used as inter-appointment medicaments must be able to penetrate through the dentinal tubules in the presence of microbes to reach a sufficiently high concentration so that bacteria will be eliminated. Microbial invasion of root canal canals system is time related and bacterial species dependent.

The goal of use of intracanal medicaments is to either the prevention or treatment of apical periodontitis^7,8 . The hand and rotary instrumentation along with irrigation will help to remove all necrotic and vital organic tissue.

Commonly seen micro-organisms are Bacteroids species, Prevotella intermedia, Peptostreptococcus microbes, Lactobacillus, Streptococcus, Propionibacterium, Enterococcus faecalis.

Intracanal medicaments are used as an aid to improve the predictability and prognosis of endodontic treatment.

INTRA-CANAL MEDICAMENTS

A medicament is an antimicrobial agent that is placed inside the root canal between treatment appointments in an attempt to destroy remaining micro organisms and prevent reinfection⁹ .Thus, they may be utilised to kill bacteria, reduce inflammation, help eliminate apical exudates, control inflammatory root resorption and prevent contamination between appointments In the treatment of teeth with vital pulp, there is no need for intracanal medication. The question of the role of intracanal medicaments becomes more relevant, and complex, in the treatment of pulpal necrosis and apical periodontitis.Accoeding to literature, many if not most root canals contain viable micro organisms after completion of the biomechanical preparation at the end of the first appointment^8,10. Therefore, a variety of intracanal medicaments have been used between appointments to complete the disinfection of the root canal. On the other hand, several appointments can also increase the risk for aseptic complications, through a leaking temporary filling and poor patient compliance.

There are many objectives. They are as follows; 

• Eliminate or destroy any remaining viable bacteria in the root canal system
• Reduce periradicular inflammation and pain 
• Eliminate apical exudates, if present
• Prevent or arrest inflammatory resorption, if present
• Prevent reinfection of root canal system by acting as both a chemical and a physical barrier if the temporary restoration breaks down.

TYPES OF INTRA-CANAL MEDICAMENTS

1. Calcium hydroxide

2. Antibiotics

3. Non-phenolic biocides

4. Phenolic biocides

5. Iodine compounds

6. Ozone

7. Laser

8. Electrochemically activated water

9. Electric current

10. Bio (active) glass

Calcium hydroxide

Calcium hydroxide has been extensively used in dentistry since 1920s.It has low solubility in water, and high pH 12.5- 12.8 and insoluble in alcohol.^11,12

Calcium hydroxide kills bacteria by direct contact through pH effects, and hence it should occupy the apical regions in a sufficient quantity to permit its biological effect to be exerted in close proximity to the appropriate tissues.Calcium hydroxide will exert an antibacterial effect in the root canal system as long as a high pH is maintained¹³ , and due to release of hydroxyl ion over time in side the root canal system. In addition to endodontic infections, use of Ca (OH)₂ has been widely advocated in dental traumatology and in the treatment of resorptions.¹¹

Mechanism of action:

1: Chemical action:

• Damage to microbial cytoplasm membrane by the direct action of hydroxyl ion 
• Suppression of enzyme activity
• Inhibition of DNA replication by splitting DNA

2. Physical action

• Acting as a physical barrier that fills the space within the canal and prevents the ingress of bacteria into the canal system.
• Ca(OH)₂ neutralizes the biological activity of bacterial lipopolysacharides and makes necrotic tissues more susceptible to the solubulizing action of NaOCl at the next appointment
• Killing the remaining micro-organisms by withholding substrates for growth and limiting space for multiplication.

The pre-treatment of root canals with Ca(OH)₂ tissue. dissolving capability of sodium hypochlorite and though the usefulness of mixing Ca(OH)₂ with CHX remains unclear and controversial, it seems that mixing Ca(OH)₂ with CHX the antimicrobial activity of Ca(OH)₂ is increased. The dentine, hydroxyapatite and remnants of necrotic pulp tissue as well as inflammatory exudates decrease the antibacterial potential of Ca(OH)₂ . ¹⁴

The disadvantages of calcium hydroxide are the difficulties associated with removing it from the root canal walls and its effect on decreasing the setting times of zinc oxide based root canal sealers.^6,11

Antibiotics

The first reported use of an antibiotic in endodontic treatment was in 1951 when Grossman used a polyantibiotic paste known as PBSC.

Locally used antibiotics become an established part of root canal disinfection and eradication of infection. The causes for the failure of antibiotics to overtake endodontic infection control are many. Many of the antibiotics used were bacteriistatic, which may prevent the growth of the micro organisms without killing them, giving the host defence a possibility to deal with the infection. However, in the necrotic canal, there is no host defence because of the lack of the circulation.So; the antibacterial effect of such antibiotics in the root canal may be only temporary. It is also possible that some bacteriostatic antibiotics can have a bactericidal effect when used in high concentrations, usually the case with locally used antibiotics.

The potential problem in the root canal with the bactericidal antibiotics may be the metabolic and physiological state of the microorganisms.Many bactericidal antibiotics are most effective when the microbial cells are in active growth phase, which may not be the case in the necrotic root canal with only limited nutrients available. Recently, the triple antibiotic paste has been used in the treatment of teeth with immature root apex and apical periodontitis.It is possible that better circulation and survival of some pulpal cells in the apical root canal are among the key factors for promising results reported so far.

Commonly used antibiotic containing commercial preparations are¹¹

- Ledermix paste. ( demeclocycline+triamcinolone)

- Septomixine Forte (corticosteroid+neomycin+polymixin B sulphate)

- The early use of calcium hydroxide following replantation has been shown to exacerbate replacement resorption due to its high pH and toxicity.

- Ledermix paste is the medicament of choice immediately after replantation as it reduces both inflammatory and replacement resorption.

A 50:50 mixture of Ledermix paste and calcium hydroxide has been advocated as intra-canal medicament in infected root canals, pulp necrosis, perforations, inflammatory root resorption and large periapical radiolucent lesions

Non-phenolic biocides

Biocides comprise a large group of diverse chemical agents that are capable of inactivating a variety of micro-organisms.

1. Alcohols - ethanol

2. Aldehydes - formaldehyde, gluteraldehyde

3. Biguanides - chlorhexidine

4. Quarternary ammonium compounds

5. Zinc

6. Phenolic compounds – essential oils

7. Phenyethers - triclosan

While antibiotics affect a specific target site in micro organisms resulting in bacteriostatic and bactericidal effects at therapeutic concentrations, biocides have a broader spectrum of activity as they work on multiple target sites^12,15. Hence bacterial resistance to biocides is unlikely to develop. The modes of action of biocides include mmembrane damage and leakage, Protein denaturation, binding of thiol groups, Initiation of autolysis, Congealing of cytoplasm contents at higher concentrations.

Factors affecting biocide activity Concentration 

• Period of contact
• pH 
• Temperature 
• Presence of organic matter.

The use of chemical agents like EDTA, polylysine will increase the activity of biocides by increasing the permeability of bacterial cell membranes.

Chlorhexidine

Chlorhexidine is used as irrigating solution as well as intracanal medicament.Recently; interest has been focused on the effectiveness of chlorhexidine in gel form or as a mixture with Ca(OH)₂ as an intracanal interappointment dressing.^16,17 It has reasonably wide range of activity against aerobic and anaerobic organisms as well as Candida species. It is more effective at alkaline than at acid pH, and its action is inhibited by the presence of soaps and organic matter.

Mechanism of action:

Interaction between the positive charge of the molecule and negatively charged phosphate groups on the bacterial cell wall. In higher concentrations it is bactericidal due to precipitation and or coagulation of the cytoplasm which is probably caused by protein cross-linking. It should be applied as an medicament between appointments for at least seven days rather than being used only as an irrigant.When used as an intracanal medicament CHX is more effective than calcium hydroxide in eliminating E.faecalis from dentinal tubules.^15,18

Phenolic agents

The Phenolic group of chemicals such as phenol, f o r m o c r e s o l , c r e s a t i n , p a r a c h l o r o p h e n o l (monochlorophenol), camphorated phenol, and camphorated parachlorophenol has a long history in endodontics as locally used root canal disinfecting agents. These medicaments have been applied either on a cotton wool pellet placed in the pulp chamber or on a paper point placed in the root canal, with the rationale being that the antimicrobial effect is delivered through vaporization of the medicament and the vapor should be in contact with micro –organisms in the canal system. CMCP is the most toxic and irritating phenolic antiseptic agent followed by Cresatin, Formocresol, and camphorated phenol. Antibacterial effect may not persist for prolonged periods of time. Concerns have been raising regarding the toxicity and possible mutagenicity of the disinfecting agents of the phenol group. In the balance of the benefits and the demonstrated and potential weakness of phenol compounds, it can be predicted that they will be increasingly replaced by other, more biological disinfecting agents.

Iodine compounds

Iodine is rapidly Bactericidal, Fungicidal, Virucidal, Sporicidal.Aqueous iodine solutions are unstable, with molecular iodine being mostly responsible for the antimicrobial activity¹⁹ .Iodophors are complexes of iodine and solubilizing agent or carrier, which acts as a reservoir of the active free iodine. 2% preparation of iodine potassium iodide is used in Endodontics.

Mode of action of iodine

Iodine attacks key groups such as proteins, nucleotides, and fatty acids, resulting in cell death.

MEDICAMENT VEHICLES

The medicament vehicle plays an important role in the overall disinfection process because it determines the velocity of ionic dissociation causing the paste to be solubilized and resorbed at various rates by the periapical tissues and from within the root canal. The lower the viscosity, the higher will be the ionic dissociation.

Types of paste vehicles

1. Water soluble substances: Water, saline, local anesthetics, ringer's solution, methyl cellulose, etc.Eg: Calxyl, pulpdent.

2. Viscous vehicles: Glycerin, polyethylene glycol, propylene glycol. Eg: Ledermix paste.

3. Oil based vehicles: Olive oil, silicone oil, camphorweed: Vitapex.

LASERS

The potential of different endodontic lasers in eradicating root canal microbes has been a focus of interest for many years.Holium;yttrium-aluminium-garnet(Ho:YAG) laser,CO₂ laser has been used in endodontics for root canal disinfection. Complete sterility still seems to remain a challenge with laser treatment. Another advantage of laser radiation in endodontics is the effect of lasers on smear layer, which may also facilitate effective disinfection of the canal. Early comparative studies however, shown that the antibacterial effectiveness of lasers in the root canal was inferior to NaOCl irrigation.^20,21

NEW DEVELOPMENTS:

Several new technologies have been introduced during last few years to improve the effectiveness of root canal disinfection. More attention has been given on the use of ozone, photoactivated disinfection with low-energy laser, electrochemically activated water, and electric current ^22,23.However, available evidence so far has failed to show that these methods would be superior or sometimes even equal to existing ones with regard to their antimicrobial effectiveness in the infected root canal.

Bioactive glass:

Research is underway in the use of bioactive glass as an intracanal medicament. In vitro, studies have shown that bioglass has antimicrobial activity against a range of microbes and that is potentiated by dentin. Recent experiment with nanometric bioactive glass indicated excellent antimicrobial effect in a human dentin model²⁴ .In one study the glass used was composed of 53% SiO₂ 23% Na₂O, 20%CaO,and, 4%P₂O₅ and was prepared from reagent grade Na₂CO₃ ,CaHPO₄ ,2H₂O,CaCO₃ and Belgian sand²⁵ .More research will be needed to evaluate the value of bioglass in root canal disinfection.

Super oxidized water:

Super oxidized water is saline that has been electrolyzed to form super oxidized water(hypochlorous acid and free chlorine radicals,).This solution is nontoxic to biologic tissues yet able to kill microorganisms²⁶. In addition to its surface disinfection capability,superoxidized water has been shown to have potential as an endodontic irrigating solution.

Biofilms affect Efficacy of Antimicrobial Agents

Biofilms are composed of micro-colonies of bacterial cells that are non-randomly distributed in a matrix of polysaccharides, proteins, salts and cell material in an aqueous solution. Bacterial biofilms are reported to be the most common cause of persistent inflammation and apical periodontitis.the presence of biofilm will affect the efficacy of antimicrobial agents since biofilms are much more resistant to such agents as result of their diffusion barriers and altered bacterial cell metabolism and replication rates. 

Mechanism of resistance of bacterial biofilms^{27, 28}

• The polysaccharide matrix retards diffusion of the antibiotic 
• Chemical changes to the environment in the biofilm where the lack of oxygen inhibits some antibiotics
• Protecting them by being located within the interior part of a biofilm. 
• Communication with one another which can influence the structure of the biofilm by encouraging growth of species beneficial to biofilm. 
• Depletion of nutrients or accumulation of waste products can result in bacteria entering a non growing state which protects bacteria from the antibiotics. 
• Biofilm bacteria existing in a low metabolic state, a slower growth rate and production of exoploysaccharides.

Biofilms and microbial aggregates are a common mechanism for the survival of bacteria in nature. The aggregation of bacteria in biofilms is likely to result in these bacteria being more resistant to antibiotics and other antimicrobials as well as being protected from the host defenses. It is estimated that bacteria grown in a biofilm have a 1000-1500 times greater resistance to antibiotics than planktonically grown bacteria. During irrigation of root canal, the outer layer of the biofilm will be directly affected by the high concentration of the irrigating solution, but the extra-cellular matrix of the biofilm may prevent the solution penetrating into the deeper layers at full strength.Endodntic instrumentation helps to disrupt and expose the full thickness of the biofilm to the irrigant solution.

CONCLUSION

Bacteria have been implicated in the pathogenesis and progression of pulp and periapical diseases. Hence primary aim of endodontic treatment is to remove as many bacteria as possible from the root canal system and then to create an environment in which any remaining organisms cannot survive. Many intracanal medicaments being tried to achieve these aims but no single preparation has been found to be completely predictable I its efficacy and hence much further research is required.

The choice of intra-canal medicament to be used during endodontic treatment is dependent on having an accurate diagnosis of the condition being treated. If the primary aim is to reduce inflammation, then cortico-steroid antibiotic mixture is indicated. Calcium hydroxide and chlorhexidine may be most ideal in infected root canal cases. Further research is required regarding the use of medicaments combined with effects of dentine on single and multiple species biofilms.