Endodontic Pharmacology

Endodontic Pharmacology

I The parietal endodontium:

The endodontium is characterized by a particular complexity from both an anatomical and histological point of view. 

• Anatomically , presence of:

• side, secondary and accessory channels
• anastomoses and apical ramifications
• Histologically: Dentin tubules can create a complex three-dimensional communication system between the canal and oral environment. They vary according to physiological and/or pathological situations.

-In pulped teeth, the tubules contain the odontoblastic extensions and the dentinal fluid which defends the pulp and opposes the penetration of bacteria and toxins.

• -In pulpless teeth, the dehydrated tubules contain only the necrotic debris of the odontoblastic processes. They can be easily penetrated by microorganisms, toxins and drugs. Mechanical root canal preparation procedures always result in the formation of a microscopic layer of surface debris called the “ smear layer ” .

• Although the exact composition of the smear layer is still unknown, it is mostly inconsistent.
• However, the presence of two following phases is undeniable:

• 1-Mineral phase consisting of dentin chips, small hydroxyapatite crystals 0.5 to 1.5μm long.
• 2-Organic phase consisting of: residues of the collagen framework of dentin and predentin, pulp debris, possibly microorganisms and their metabolic products (toxins, enzymes)

-For all this intracanal complexity, only the mechanical action of the instruments does not allow satisfactory canal trimming to be achieved. 

-Irrigation is essential to achieve this goal:

Mechanical action + chemical action = concept of bio-chemo-mechanical preparation. 

II- Endodontic irrigation 

1) Definition of irrigation:

• According to Grossman : action of eliminating by washing with an irrigation solution all organic, mineral and microorganic debris detached and suspended by mechanical instrumentation.

2) Required properties of an irrigant:

1. Mechanical properties: 

• Lubrication of instruments, which helps with root canal debridement
•  Suspending debris to facilitate its removal
• Cleaning the canal walls
• Helps prevent the formation of dentin debris plugs

2. Chemical properties

• Wetting action, by lowering the surface tension
•  Solvent action on organic and mineral tissues:

           • On the content: solubilization of organic debris, cellular and bacterial debris, exudates from the main and accessory channels

           • On the container: elimination of dentinal smear

3. Biological properties:

•  Biocompatibility
•  Antiseptic action: bactericidal and virucidal action

Endodontic Pharmacology

3) Products used: 

3.1)Sodium hypochlorite (NaOCl)

• Discovered in the 18th century (bleach), used in the textile industry for whitening
• Cl2 + 2 NaOH NaOCl + NaCl +H2O

Other derivatives : Sodium dichloroisocyanurate

• Mode of action

1. Saponification reaction: Sodium hypochlorite acts as an organic and fatty solvent that degrades fatty acids and transforms them into fatty acid salts (soap) and glycerol (alcohol.
2. Neutralization reaction: Sodium hypochlorite neutralizes amino acids forming water and salt. 
3. Formation of hypochlorous acid : When chlorine dissolves in water and comes into contact with organic matter, it forms hypochlorous acid (HOCl−) and hypochlorite ions (OCl−) lead to the degradation of amino acids.
4. Solvent action:

Sodium hypochlorite acts as a solvent, releasing chlorine which combines with protein amino groups (NH) to form chloramines. Chloramines thus hinder cellular metabolism by inhibiting bacterial enzymes. 

4. High pH :

Sodium hypochlorite is a strong base (pH > 11). Its antimicrobial efficacy is related to the high pH that interferes in the integrity of the cytoplasmic membrane, biosynthetic alterations of cellular metabolism and phospholipid degradation observed during lipid peroxidation

• Concentration 

• NaOCl is used at concentrations between 0.5% and 6% for root canal irrigation.
• Starts to be effective from 1%;
• the most used solution in OCE is 2.5% which is obtained by mixing one dose of NaOCL solution at 13° with 1.6 doses of distilled water 

• Volume  : Frequent change of fresh NaOCl is important and using a large amount of irrigant compensates for the low concentration. It should be remembered that NaOCl will inactivate its components very quickly
• Reaction time: Some articles will show bacterial destruction in 30 minutes when 0.5% NaOCl is used, while concentrations of 5 and 6% will only need 30 s to do the same job. It is important to remember that the presence of organic matter, inflammatory exudates, tissue remains and microbial biomass consumes NaOCl and weakens its effect.
• Effect on dentin: NaOCl can affect the mechanical properties of dentin via the degradation of dentin type I collagen.
• Penetration depth: The penetration depth of NaOCl ranged from 77 to 300 μm, and it depends on concentration, time and temperature. 
• Effect on biofilm: 3% and 6% NaOCl solutions showed absence of biofilm while 1% NaOCl showed disruption of biofilm
• Temperature

• Increasing the temperature of low concentration NaOCl solutions improves their immediate tissue dissolution capacity. The bactericidal effect 
• There are various devices for
  • preheat the NaOCl syringes 
  •  in situ heating of NaOCl by ultrasound 
• Limitations and adverse effects of NaOCl

• NaOCl is toxic and has an unpleasant taste, 6% solutions are the most toxic.
• If NaOCl is combined with chlorhexidine, an orange-brown precipitate is formed based on parachloroaniline (PCA), which can be mutagenic, 
• If NaOCl is mixed with EDTA, it loses its antibacterial effect. 
• If NaOCl is used again after EDTA, it causes erosion of the root wall which harms the mechanical qualities of the root 
•  Extrusion of NaOCL beyond the apex can cause significant tissue damage, 

3.2) Chlorhexidine digluconate

• Antimicrobial efficacy of 0.2 to 2% with a very broad spectrum, in the form of gluconate, fungicide and weak virucidal action 
• Low solvent action
• No action on the smeayer layer
• Reduced action in the presence of necrotic tissues, inflammatory exuda 
• Low toxicity and substantivity effect (long-term continuous effect) 
• It can be used as a final rinse after using EDTA 
• Synergistic effect when combining CHX with hydrogen peroxide
• Indicated especially in patients with intolerance to hypochlorite (2% gel)
•  CHX forms a salt with EDTA rather than undergoing a chemical reaction
• CHX forms a highly mutagenic complex in association with NaOCL.

Endodontic Pharmacology

3.3) Iodine potassium iodide

• They are used for decontamination of surfaces, skin and operating fields.
• It exhibits bactericidal, fungicidal, tuberculocidal, virucidal and even sporicidal activity.
• Less effective than NaOCL
• Reduced effectiveness in the presence of dentin; tissue and cellular debris
• Low solvent action   

3.4) Oxidizing products

Hydrogen peroxide H202 at 10 vol. (3%)

• Antiseptic effective on anaerobic germs, ineffective on aerobes
• Effervescent effect: elimination of debris
• Sometimes combined with other products such as 5% hypochlorite
•  Poor biocompatibility, as it causes apical inflammatory reactions
•  Hemostatic
• Lightening action.
•  little used by some practitioners

Urea peroxide:

•  In the form of crystalline powder to be mixed with physiological serum
• Good antiseptic
•  Lubricating action
• Good biocompatibility, no inflammatory risk
• Little used

3.4) Chelating agents:

• EDTA (Ethylene Diamine Tetra Acetic Acid)
• Action by demineralization of dentin: they facilitate the penetration and widening of fine and mineralized canals.
• The active molecule replaces the calcium ions Ca+ and causes precipitation of soluble salts, which leads to demineralization of the mineral framework. 
• The frame is weakened, the walls are less hard and boring is easier.

Chelators in liquid form:

• Allows chemical removal of smear layer
•  Associated with a product improving the wettability of the liquid (surfactant, ammonium type IV) and therefore increasing its penetration into the dentinal tubules
•  No antiseptic action of its own
• Ex: the Largal

Chelators in paste form

• Same mechanism of action
• Foaming effect on contact with hypochlorite 
• Ex: GlydePrep®, Canal+®: EDTA mixture with glycerin and urea peroxide used per-operatively
•  Important lubrication with glycerin
•  Widely used in endodontics
• 6% citric acid

– Chelating action

– Eliminates the smear layer without excessive demineralization of the tubules

3.6) BioPure MTAD and Tetraclean

• MTAD, introduced by Torabinejad and Johnson, consists of an aqueous solution of 3% doxycycline, a broad-spectrum antibiotic; 4.25% citric acid, a demineralizing agent; and 0.5% polysorbate detergent.
•  Tetraclean (Muggio, Italy) is similar to MTAD. The two irrigants differ in the concentration of antibiotics (doxycycline 150 mg/5 ml for MTAD and 50 mg/5 ml for Tetraclean) and the type of detergent (Tween 80 for MTAD, polypropylene glycol for Tetraclean).
• Use in final rinse
• These irrigants are able to remove both the smear layer and organic tissues from the infected root canal system. 

3.7) QMiX

• QMiX contains a CHX analogue, triclosan (N-cetyl-N,N,N-trimethylammonium bromide) and EDTA as a decalcifying agent.
• Use for final rinse

3.8) Ozonated water

• Ozone is a chemical compound composed of three oxygen atoms (O3, triatomic oxygen), 
• Ozone is a powerful bactericide
• Possibility of bubble formation that causes implosions upon contact with the surface of the canal walls, such shock waves could potentially disrupt bacterial biofilms, rupture bacterial cell walls and remove the Smeayer Layer and tissue debris. 
•  Ozonated water is less effective on Escherichia coli and lipopolysaccharides inside the root canal. 

3.9) electrochemically activated water

• It was developed by Russian scientists at the All-Russian Institute of Medical Engineering in Moscow.
• By using a flow electrolytic module (FEM) in a saline solution 
• FEM is capable of producing solutions that have bactericidal and sporicidal activity through the formation of a solution called superoxidized water. 
• Superoxide is not toxic when in contact with vital biological tissues.
• Superoxide effectively removes the smear layer
• low allergic reaction 

3.9) Photo-activated disinfection

• Methylene blue and tolonium chloride have been used as photosensitizing agents to ensure root canal disinfection.
• Methylene blue in combination with red light (PAD) was able to eliminate 97% of bacteria including E. Faecalis 
•  FotoSan is one of the most recent PAD devices introduced in endodontics
• 4) Irrigation techniques:

A- Manual method

• The necessary equipment consists of a plastic syringe and a disposable needle plus a surgical suction device. 
• The method is based on the principle of Contact-Withdrawal-Ejection
• Place the needle stop at the working length -3mm
• The needle is inserted into the canal until it is blocked by the canal walls. It is then withdrawn 1 to 2 mm, thus creating a reflux space for the solution.
• In this position, the solution is ejected under very low pressure. 
• The solution drains to the coronary orifice and is collected by surgical suction.

Endodontic Pharmacology

B- Apical negative pressure irrigation:

1.EndoVac® 

• The irrigation solution is deposited into the pulp chamber using a macro cannula and aspirated to the end of the canal through a fine perforated needle, which allows a hydraulic circuit to be established when the solution rises there.
• low risk of apical extrusion of solutions
• Reduced postoperative pain
• Good debris evacuation 

2. RinsEndo ® 

• The RinsEndo works with an injection-aspiration mechanism of the irrigation solution.
•  This is a handpiece connected to the turbine connector on the dental unit
• It presents a risk of apical extrusion 

C- Irrigation by sonic and ultrasonic system  

1. Passive ultrasonic irrigation 

• Passive intermittent ultrasonic irrigation involves performing several fillings of the canal with the irrigating solution and implementing several activation cycles with the ultrasonic file.
• Warms the hypochlorite solution and potentiates the antibacterial effect 
•  Effective in removing root canal debris 
• Ultrasonic files should only be used when the preparation is completely complete to allow deep insertion without direct contact with the canal walls.

2. ProUltra® PiezoFlow® (Continuous Ultrasonic Irrigation)

Continuous ultrasonic irrigation performed uses a specific ultrasonic unit with a handpiece on which a 25 G needle is welded which delivers the solution and vibration at full power

3. EndoActivator®

• It is a cordless sonic handpiece, which allows to activate the vibration of flexible and resistant plastic inserts that conform to the final canal preparation at a frequency of 10,000 cycles per minute.
• The EndoActivator® tip is used at 1 mm from the working length with a short vertical back and forth movement for 11 minutes after instillation into the canal of 1 ml of EDTA and for 30 seconds after instillation
• Effective in removing root canal discharge, calcium hydroxide and remaining filling materials in case of retreatment  

4. Vibringe® Syringe 

It is similar to a manual syringe for delivering irrigation but, being battery-powered, it generates sound vibrations at the needle at a frequency of 9,000 cycles per minute. 

5. GentleWave® 

• It consists of a central unit from which high-pressure pumps send a high-speed discharged irrigation flow to a special handpiece with a tip of the handpiece placed in the pulp chamber.
•  The irrigation current propagates in the form of a cloud to the canal system. 
• According to the manufacturer, the effect is based on broad-spectrum sound energy. 
• The irrigant is drawn through several small holes in the handpiece covering the access cavity, and creating a stable negative pressure throughout the root canal system.

D- Root canal disinfection by LASER   

• Several lasers have been used for root canal disinfection (Ho: YAG), CO2 and Diode laser, the latter has proven effective against 99.98% of bacteria and acts effectively on the dentinal smear.
• (PIPS™) is a new technology using laser-activated irrigation has been introduced. Photon-induced photoacoustic flow uses a low-energy Erbium laser to generate a photoacoustic shock wave throughout the root system without the need to enlarge the canals 

E- Irrigation by antibacterial nanoparticles 

• Nanoparticles are microscopic particles having one or more dimensions in the range of 1 to 100 nm.
• . Antibacterial nanoparticles have a broad spectrum of antimicrobial activity and low microbial resistance than antibiotics.
• They can be mixed with irrigants, photosensitizer and root canal filling materials.

F- Suggested disinfection protocol

The following steps are most commonly used:

1.  irrigation with 2.5 to 5% NaOCl throughout the canal instrumentation until the final canal shape is achieved (needle is placed 3 mm from the LT without blockage ).
2.  Activation and heating of fresh NaOCl (by gutta cone, ultrasound, sonic or laser) for approx. 30. 
3. Apical negative pressure devices are optional to enhance apical irrigation without extrusion (eg Endovac).
4. Root canal rinsing with (EDTA, citric acid, etc.) for approx. 1 min
5. final rinse:
   1. a. Fresh NaOCl for approx. 1 min or
   2. b. CHX, QMiX or
   3. c. Alcohol or
   4. d. Dry with paper points and seal

III- Temporary intracanal medications  

A- Calcium hydroxide:

Calcium hydroxide with the formula Ca(OH)2, also called hydrated lime, disintegrated lime or slaked lime, comes from mixing quicklime (CaO) and water.

It is a fine, white, unstable crystalline powder which, upon contact with air, transforms into calcium carbonate. Its pH: Varies from 9.5 to 12.5.

Presentation:

• Masterful formula:

The CaOH2 powder is mixed with any solution: saline solution, anesthetic solution without vasoconstrictor or distilled water on a glass plate until a homogeneous paste is obtained. The perfectly dry canal is closed using a Lentulo paste plug or a pin up to the limit previously determined by an X-ray.

• Commercial preparations: in the form of dough presented in a syringe with tips e.g.: Endocal
• CaOH2 cones: 

• Points composed of gutta-percha (42%), calcium hydroxide (52%), sodium chloride, a wetting agent and color pigments. 
• – Ready-to-use tips, stable in shape but flexible enough to allow easy insertion, even into curved root canals.

Properties 

• Antiseptic action: with a pH of 11, a calcium hydroxide paste has an antibacterial effect, no pathogenic microorganism in the endodontium could survive at this pH.
• Anti-inflammatory action  CaoH2 counteracts the action of osteoclasts by opposing acidosis, 
• -Osteoinductive action  : this cement is capable of causing the formation of calcified barriers (newly formed hard tissues).
• -Hemostatic effect  : the hemostatic properties are due to the presence of Ca+ ions which could decrease capillary permeability leading to a significant decrease in plasma fluid.
• Anti-exudative action: The anabolic effect of CaOH2 on periapical tissues helps to combat serosity and intraductal exudates.
• Sedative action: Not overlooked property due to the release of salicylates during the progressive solubilization of the product.

B-Chlorhexidine digluconate

• CHX can be used in the form of 2% gel as intracanal medication 
• CHX mixed Ca(OH)2 is much more effective in disinfecting dentin infected by E. faecalis and C. albicans yeast 

C-Bioactive Glass

• Research is underway into the use of bioactive glass as an intracanal drug.
•  The glass used was composed of 53% SiO2, 23% Na2O, 20% CaO and 4% P2O5
•  When used in root canals , bioactive glass kills bacteria, the mechanism of which remains unclear. 

D- Disinfectants:

1-Phenols and compounds:

• Phenol is a protoplasmic poison that causes protein coagulation .
• It is a volatile product
• Analgesic 
• Very irritating to living tissues
• ex: CPCM walkoff (Parachlorophenol, camphor and menthol)

2-Mercryl:

•  composed of: Mercurolentol, laryl sulfate and Na, 
•  antifungal activity: on candida-albicans.
• Broad spectrum bacteriostatic activity, particularly on gram+ cocci

3-Aldehydes:

 Formaldehyde: Powerful antiseptic, toxic but combined with cresole or thymol, it becomes less irritating.

 Glutaraldehyde:   Is less volatile than formaldehyde, its irritant power is considerably reduced.

Currently, formalin products (OSOMOL type) are contraindicated and should no longer be used in endodontic treatment.

E- Antibiotics:

• Ex: Grinazol (metronidazole) and Septomixin (polymyxin sulfate, neomycin) and Cortexan (framycetin sulfate), 
• Sometimes combined with anti-inflammatories.
• They are introduced into the canal using a paste or a pin.
• No longer used due to allergic reactions, sensitization and resistance .

Endodontic Pharmacology

F- CORTICOSTEROIDS:

• They significantly reduce pain (Dexametasone).
• They decrease immunity which makes the periapex more susceptible to infections
•  These drugs are toxic agents acting locally  
• their systematic use as intracanal medication is not recommended.

E- sedatives:

Pulperyl:

The endodontium is characterized by a particular complexity from both an anatomical and histological point of view. 

• Anatomically , presence of:

• side, secondary and accessory channels
• anastomoses and apical ramifications

Histologically: Dentin tubules can create a tri-communication system

Endodontic Pharmacology

  Untreated cavities can reach the nerve of the tooth.
Porcelain veneers restore a bright smile.
Misaligned teeth can cause headaches.
Preventative dental care avoids costly treatments.
Baby teeth serve as a guide for permanent teeth.
Fluoride mouthwash strengthens tooth enamel.
An annual checkup helps monitor oral health.
 

Endodontic Pharmacology