بسم ال الرحمن الرحيم
Introduction: • The references for this lecture are the record,&the slides • The Dr announced in this lecture that every student have to search about the mechanism of action of chlorhexidine as bactericidal& the reasons of discoloration that caused by its use,and this homework will be part from your quiz mark. • All underlined informations are copied from the slides • L.D.D.D stands for local delivery drug device,GCF :gingival crevicular fluid,CHX MW:chlorhexidine moush ..………………………………………………………………………Now let's start As we know periodontal diseases are initiated by bacteria (dental plaque) and from this point of view we use antibiotics in the treatment of the periodontal ,diseases Last time we talked about systemic chemotherapeutic agents specialy antibiotics ;today we will continue talking about local application of .antimicrobial agents
(Local delivery drug device(L.D.D.D Any dental instrument that used to deliver drugs localy under certain rules(we will see later),this is very important concept so if you want to practice . periodontics your treatment will be much more selective for certain cases Periodontal diseases comprise a group of chronic inflammatory disorders with bacterial etiology that results in breakdown of the connective tissue Safe & intrinsically efficacious medications can be delivered into periodontal pockets to suppress or eradicate the pathogenic microbiota or modulate the inflammatory response as we can give our pt systemic antibiotics to treat periodontal diseases we can also safely introduce antimicrobial agents inside the . deep pockets and this is what we want to concentrate on in this lecture Local vs systemic application of antimicrobial agents :Advantages of local antimicrobials 1
More concentration :the most important advantage of the local application√ of antimicrobial agents ,I can provide high concentration without any side effect ,coz as we know the problem with systemic antibiotics in the treatment of periodontal diseases as an adjunct to scaling and root planning is that we are limited with concentration that reach to the base of the pocket via serum or via the GCF and this concentration inspite that it is effective in reducing or killing bacteria but it does not reach concentration beyond 12µg/ml which is very low concentration but in LDDD we can provide very high concentration of the antimicrobials inside the periodontal pocket For effective periodontal .treatment by antimicrobial agents, there is a need for a high conc . . fewer side effects:we can avoid S/E that assosciated with systemic antibiotics√ substantivity:you can not benefit your pt from this property if he takes the√ antibiotic systemicaly ,but local application and binding or adsorbing to the mucosa or the root of the tooth and then it will be elaborated to the pocket when the concentration of the free antibiotic getting reduced. Some of them including TET.s & CHX pocess this important property which is substantivity Pt compliance : pts are more compliant with this sort of antibiotic delivery√ .than with systemic antibiotics And finally there is . NO risk of bacterial resistance as with systemic antibiotics √ :the disadvantages of local antimicrobials more chair side more expensive No effect on bacterial reservoir :this means that for certain periodontal diseases such as aggressive periodontitis the bacteria resides deep in the gingival connective tissue and these sites can not be reached by local application of antibiotics, its only can be reached by serum through systemic . administration Now the rules for local application of antimicrobial agents for the treatment of :periodontal diseases are The medication must reach the intended site of action:this site in our .1 . case in the periodontal treatment is the base of periodontal pocket :Remain at adequate concentration .2 Last for sufficient duration of time.3 2
Any device that achieve the above 3 rules we can consider it as LDDD . for periodontal treatment In the past &till now in the practice periodontists are using some methods thinking they are using LDDD for example:many dentists and periodontists take CHX MW pull it by hypodermic syringe ,bend the needle ,insert the needle alittle bit in the periodontal pocket and inject the material and this is called SUBgingival irrigation ,this method could achieve the 1st point which is reaching to the intended site of action & it might achieve the 2nd point which is I provide the area with high concentration BUT it does not achieve the 3rd point which is sufficient duration WHY …………….we will see why……………… ((the answer is alittle bit long
: 1st we will talk about the importance of the 1st two rules Site of action: Bacteria residing in periodontal pocket Soft tissue walls of the pocket ,The exposed cemetum or radicular dentin all of these areas have bacteria and their products that need to be reached locally but not all antimicrobial agents can reach these areas ,such as mouth :rinses &supragingival irrigation ,very nice illustration in slide #8
There are many devices in the markets saying that you can use some sort of SUPRAgingival irrigation as aiding in mechanical plaque control,but these devices are used wrongly in SUBgingival irrigation and applied to the pocket as L.D.D.D by some dentist 3
In this slide starting from upper left picture ,as you can see(I hope you can!!!)(supragingival irrigation) can reach from 29-71%of the gingival sulcus (no deep pockets but there is gingivitis) and that is why using CHX MW in the treatment of gingivitis as an adjunct to scaling is very effective,now if you treat deep periodontal pocket with SUPRAgingival irrigation it will not reach more than 65%of the depth of the pocket (upper right picture)and our site of action is the base of the pocket,also if you use these antimicrobials for SUBgingival irrigation it will not reach more than 70-90%of the depth of the pocket also not effective for the same reason –90%is deep enough but we will see later what is the wrong with this-(lower right &left picture),finaly the most right picture shows how using of mouth rinses (as mouth wash not for irrigation) in the deep periodontal pockets is useless ,not more than 4%of the pocket depth and this is nothing (so you can not prescribe CHX MW in the treatment of active,destructive periodontal diseases with deep pockets as an adjunct to scaling and root planning coz it is simply can not reach more than 4%of the pocket BUT IF YOU PRESCRIBE IT TO HELP THE PT TO PRACTICE GOOD MECHANICAL PLAQUE . CONTROL SUPRAGINGIVALY THEN IT IS OKAY Back to subgingival irrigation using as we said hypodermic syringe &needle with antimicrobial agents may reach depth of 90%of the pocket BUT there is something called periodontal clearance ,it means GCF replaces itself 40 times each hour which means if you provide the area with some concentration it will be the half of its beginning after 1 hour (I don't know how!!)due to continuous clearance .of GCF inside the pocket So you need a certain reservoir,certain material that maintains inside the periodontal pocket continuously despite of periodontal clearance this point can not be achieved by subgingival irrigation ,so the devices that are present in the markets as L.D.D.D are not MW neither liquids inserted in the periodontal pocket ,but they are the materials that achieve the 3 rules of L.D.D.D and containing . substantive materials :Now what is the definition of L.D.D.D L.D.D.D. : consists of a drug reservoir and a limiting element that controls the rate of medicament release The goal is to maintain effective conc. of chemotherapeutic agents at the site of action for long periods, despite drug loss from G.C.F. clearance 4
according to the duration of medicament release )we can classify ) L.D.D.D into 1.duration less than 24 hours( Sustained release (devices (duration exeeds one day.(Controlled delivery devices.2 & We are seeking for a device what we call it CONTROLLED local drug delivery device in which it gives us the effective concentration of .the drug inside the pocket for more than 24 hours These are generally the delivery systems with regulatory approval by the ( FDA ) or the regulatory bodies of the European Union At present 5 products are commercially available Tetracycline fibers (Actisite®, Alza corp., Mountain view, (.C.A Metronidazole gel ( Elyzol®, Dumex, Copenhagen, ( Denmark (.Minocycline gel (Arestin®,Lederle,U.K (®Chlorhexidine chip (Periochip Doxycycline hyclate in a resorbable polymer (Atridox®, Collines, Co.)we mention the companies coz they are the only companies that .produce these products
Notice that 4 of these5 antimicrobial agents have substantivity property (tetracyclines &CHX)and the other metronidizole is for . its anaerobic action Before we talk about each one separately it is very important to ??know when &where I use L.D.D.D Not every pt after you finish examination you provide him with L.D.D.D,there is role of application coz as we said it takes more chair side &it is very expensive (the syringe of atridox costs :200$)so Role of Local Delivery of Antimicrobials Localized sites of inflammation associated with PD> 5mm that did not respond to S&RP and are not eligible for surgery
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Localized sites of inflammation associated with recurrence or persistence of PD > 5mm in maintenance patients(deep (pockets with bleeding on probing Surgery is unpredictable or undesirable Used as an adjunct to mechanical therapy and not as a substitute 1st one that we will talk about is tetracycline fibers(you will see why (these fibers are not used any more in the practice
®actisite Non resorbable cylindrical L. D.D.D. made of – . a biologically inert,plastic copolymer loaded with 25% Tetracycline. HCL powder.(very high concentration 1300 times the concentration (provided by systemic capsules The fiber is applied to completely fill the pocket Maintained in situ with a cyanoacrylate adhesive for 7 –10 (days, conc. excesses 1,300 ug/ml .(slide 14 ???????????????BUT why this material is not used any more first :Some pts are not compliant with the dentist or the periodontist and do not come to remove the non-resorbable fiber after 10 days ,so they will experience periodontal abcess coz .(empty fibers are forign body (the most important reason Second:due to the high concentration of the tetracycline in these fibers some pts may experience fungal infections when they have . more than 4 sites provided by tetracycline fibers Now with the most effective L.D.D.D &has the best research : studies&clinical results is :Atridox doxycycline hyclate gel(very high concentration equal to 10% (1000 times the conc. provided by the capsules This gel consistency is the resorvire that we talked about Mixed and Injected into the site it takes the shape of the pocket Continued release for 7 days Biodegradable it will resorb by itself 6
:Needs training but relatively simple to use It comes in the form of two syringe one of them contains the powder and the other contains the liquid then the components will be mixed together in a certain way –that funny way!!-until the mix become in the gel form then you insert it in the pocket until you see the pocket slightly swollen then you should provide the orifice of the pocket with some sort of glue to prevent the material from slippage out ,then you examine the pt after two week to see the results ,and very important to remember that you . should apply the gel after scaling &root planning Periodontal clearance will not affect this process ,coz this gel contains high conc. of the antimicrobial agent ,even with .periodontal clearance ,and the substantivity very high for atridox Now(slide#17) this is a case that came to the Dr clinic ,was diagnosed with aggressive periodontitis,after the Dr has treated the pt with scaling &root planning ,there is still some areas with severe recession, deep pockets &bleeding on probing which means that the disease is active in the maintenance phase, the Dr can not provide her with any sort of periodontal surgery coz it will make the recession longer ,then atridox was applied inside the pocket ,as you see in( slide #18)the pocket is slightly swollen,then we place adhesive material(cyanoacrylate) at the orifice of the pocket so when you apply L.D.D.D correctly to where it should be applied you .(will have 100%success rate(slide 19 afetr atridox ,upper picture : Another type of L.D.D.D provided in the markets is Arestin Is a bioabsorbable sustained delivery system consisting : of Minocycline HCL in a matrix of Hydroxyethyl ( 2% ) cellulose (Amino alkyl methacrylate(as adhesive Tryasitian & glycerin Magnesium chloride is added to modify the drug release properties Bacteriostatic antibiotic , no data regarding the period of it’s reservoir :the Dr read what is written in the pruchore of this drug :Clinical use 7
Periodontitis with pockets >= 5 mm(and sure that don not (respond to scaling &root planning and not eligible to surgery
:How supplied Box containing 2 trays each containing 12 cartridges Cartridge contains 1 mg of minocycline (semisynthetic tetracycline derivative) microencapsulated in Poly dry powder Cartridge inserted into a cartridge handle :Mechanism of action Broad spectrum Bacteriostatic G.C.F levels maintained at high levels for at least 14 days As you see in slide #23,figure 1 snap,figure 2 inject the material ,(inside the pocket(it comes as spheres of gel :Another type is (®CHX chips(periochip As we all know the concentration of CHX MW is 0.2%,imagine that the concentration of the CHX in the biodegradable chips is .(2.5mg (very high concentration Used only in pockets > 5 mm Insertion could be challenging, it should be gently pushed into pocket .In slide #25 this is periochip kit ,each kit contains 10chips Due to its shape &width it can not be inserted at any pocket(look slide#26)it needs pockets with large width to be inserted in, (slide#27)in this slide there is wide pocket with missing adjacent .tooth suitable for CHX chips Very delicate chips when it get alittle moisture it will shrink by itself,so you should train yourself very will to apply it immediately .in its correct position Q:CHX is not an antibiotic ,so how we use it to kill bacteria in the ???deep pockets 8
Dr:it is an antimicrobial-MOA is homework-mainly bactericidal it can kill bacteria inside the pocket ,but you can not kill this bacteria using CHX MW coz as we said it can not reach more than .4%of the pocket depth,and in low conc.0.2% :Now we have finished L.D.D.D and we will talk about CHX MW Forms: digluconate , acetate and hydrochloride salts.the 3 first two are water-soluble Palque inhibition was first investigated in 1969 by Schroeder The definitive study was by Loe& Schiott 1970: showed that rinsing with 10ml of 0.2%(20mg dose) twice daily in absence of normal tooth cleaning inhibited plaque regrowth and development of gingivitis As you see in slide #29 this the form of CHX
Bisguinide antiseptic Strong base & dicationic at pH above 3.5 ◊ extremely interactive with anions(as you know cations are +ve&anions (are –ve Minimally absorbed through skin or mucosa◊ no systemic toxicity Can cause neurosensory deafness if introduced into the middle ear Has a broad antimicrobial action,G+ve & against some fungai & yeast as candida ,and against some viruses including HBV & HIV No reported bacterial resistance with long term use
Chlorhexidine/ Side effects Brown discoloration of teeth,dorsum of tongue and restorative materials( staining of the teeth is exogenic can be removed by scaling & polishing and this stainig has a certain cause and part of this cause depend on your instructions of use that you give to your pt ,you should instruct the pt to rinse 30 mins after brushing not immediately and not to eat or drink for 30 mins), In slide #32 you can see brown discoloration of the teeth &the . tongue Taste perturbation mainly salt taste◊ bland taste (Oral mucosa erosion(slide 33 pic.on the left side 9
Unilateral or bilateral parotid swelling???(pic. On the right (side ?Enhanced supragingival calculus formation Has a bitter taste CHX FORMS Mouthwashes: 0.2,0.1 and 0.12% use 15ml 0.12% equal to 10 ml 0.2% Gel: must be delivered to all tooth surfaces .Sprays: for physically or mentally handicapped Toothpaste :difficult to formulate Varnish: for root caries prevention Chlorhexidine/ uses As the dr noticedc that we prescribe CHX MW haphazardly in the :clinic,so he said that we should know these indications very well Adjunct to OH and professional prophylaxis(the most (important Postoral surgery Jaw fixation Mentally and physically handicapped Medically compromised predisposed to oral infections High-risk caries Recurrent oral ulcerations orthodontics appliance Denture stomatitis Immediate preoperative rinsing Subgingival irrigation Chlorhexidine/conclusions Chlorhexidine to date is the proven most effective antiplaque agent for which commercial products are available to the public(so any new MW when you want to make certain study on it either you test the material with placebo has the same color ,taste,shape of the new product if the new product gives better results then I consider it as more effective than the placebo!but this is not enough to say that this product is effective against gingivitis and plaque accumulation,the research says that 10
you should test it with another material-positive control-which is . CHX MW Chlorhexidine is free from systemic toxicity in oral use, and microbial resistance and supra-infection do not occur Local side effects are reported which are mainly cosmetic problems The antiplaque action of chlorhexidine appears dependent on prolonged persistence of antimicrobial action in the mouth (substantivity A number of vehicles for delivering chlorhexidine are available, but mouthrinses are most commonly recommended Extrinsic dental staining &perturbation of taste are variably the two side effects of chlorhexidine mouthrinse usage which limit acceptability to users and the long-term employment of this antiseptic in preventive dentistry :Finaly we will talk about tooth paste The Dr said that We should know the components of tooth paste,coz your answer for the next week homework why I should not give CHX MW immediately after brushing?which means that there is certain ingredients in the tooth paste that counteract the action of CHX ………MW……search more about In slide #41 you can see why some tooth pastes come striped with different colors …..coz it is coated from the inside with the green or red material…and the white material in the middle so when the TP .squeezed two colors will exit from the tube Benefits of toothpastes :The Dr read them from the slides Caries control Fluoride is available in a range of concentrations 250.2800 ppm F]≤ 600ppm → children ≤7years with low caries] .incidence 11
F] =1000ppm → children ≤7 years with high caries] risk .F]1000-1500ppm → all individuals 7 years and above] F]2800ppm→ high risk adults and elderly] Gingivitis and
: periodontitis Triclosan is the most widely used antimicrobial It also has anti-inflammatory properties &thus could reduce gingival inflammation independent of its effect on plaque :Dentine sensitivity Strontium chloride 10% Potassium nitrate Potassium citrate Stannous fluoride Anti calculus))Anti-tartar Soluble pyrophosphate Zinc salts Triclosan Whitening The main action is through abrasive removal of extrinsic stains Whitening toothpastes Abrasives Macleans whitening, colgate platinum Oxidizing agents Brilliant whitenning system,Rapid white Enzymes Rembrandt original Detergents .Aquafresh whitening EDTA Boots advance white : Tooth tips 12
Choose a toothpaste that is fluoridated, brush for 2 minutes at least twice daily Studies suggested that bacteria regrow on clean teeth about 4 hours after brushing -> brush and floss regularly The mechanical action and the technique of brushing are much important than the brand of the toothpaste The most common question the pt will ask you about the best type of tooth paste that he/her should use ?your answer should be that the name of the brand is not as important as the technique of brushing UNLESS your pt want the TP as vehicle of a medication (CHX,fluoride ,desensitizing agent…..etc)then you .should recommend your pt with the suitable type
conclusions Current data suggest that L.D.D of antimicrobials into a periodontal pocket can improve periodontal health Monotherapy with them is questionable , adjunctive use of L.D.D.Dmay enhance the results in sites that don’t respond to conventional therapy L.D.D.D. should only be used in specific areas were conventional forms of therapy may fail to control infection So it should not be used routinely in situations when efficacious results can be accomplished with S&RP The end Your colleague:Heba.A.Ali Special thanx to AaAyYaA & S7R for help .……………………Good luck in the exams
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