Perio Lec.5

‫بسم الله الرحمن الرحيم‬

Chemotherapeutic agents in periodontal diseases Today we will talk about the antibiotics and mainly the systemic. The idea of treating the periodontal disease by antibiotics came from the fact that this disease is bacterial disease, but the problem is from the cause that is the plaque, this plaque is composed of biofilm that contains layers of bacteria that are communicating with each other in the pocket, so this feature of biofilm make it difficult for the antimicrobial to reach the bacteria in effective concentration, so the most effective treatment of periodontal disease is the mechanical debridment, and removal of all the factors that cause plaque accumulation. There are some periodontal diseases in which the bacteria are not only in the plaque but the bacteria are residing in the periodontal connective tissue, so in these cases the use of chemotherapeutic agents is very important as an adjunctive to mechanical debridment.

Definitions: Chemotherapeutic agent: is a general term for chemical substance that provides a clinical therapeutic benefit. The benefit comes from two things: the antimicrobial effect and from increasing the host's defense, because the destruction in periodontal diseases come from bacterial toxins and from the host defenses, so we have drugs that act on the bacteria and drugs that act on the host defenses as we will see later in this lecture. Antimicrobial agent: is a chemotherapeutic agent that works by reducing the number of bacteria present Antibiotics: are naturally occurring, semi synthetic or synthetic types of antimicrobial agents that destroys (bactericidal) or inhibits the growth (bacteriostatic) of selective microorganisms, generally at low concentration. Antiseptics: are chemical antimicrobial agents that are applied topically or subgingivally to mucous membranes, wounds, or intact dermal surfaces to destroy microorganisms and inhibit their reproduction or metabolism and these could be Antiplaque, antigingivitis mouth rinses or dentifrices (could be bactericidal as chlorhexidene or bacteiostatic). Disinfectant: a sub category of antiseptic that are generally applied to inanimate surfaces to destroy microorganisms that we use for disinfection of the clinic.

Chemotherapeutic agents: We can use chemotherapeutic agents systemically or locally.

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Our chemotherapeutic agents to be effective they should reach the base of the periodontal pocket, and this can happen either from the blood supply (systemic) or directly through a syringe (local). The systemic antimicrobial agents should be used in aggressive periodontitis especially the localized. The benefits of the use of local application of antimicrobial agents are: • The high concentration of antimicrobial in the pocket that can decrease the number of bacteria. • This prevents the bacterial resistance. • Reduce possible side effects. Chemotherapeutic agents can have a dual mechanism of action: for example Tetracycline can reduce collagen and bone destruction through it's ability to inhibit enzyme collagenase. When we talk about treatment of periodontal diseases we should keep these points in our minds: 1. The treatment of periodontal diseases is based on the infectious nature of these diseases Ideally the causative microorganisms should be identified and the most effective agent selected using antibiotic sensitivity test. 2.

It is difficult to identify specific etiologic microorganism(s) rather than microorganisms simply associated with various periodontal disorders, so there are complex periodontal pathogens that cause the periodontal diseases, and no specific antimicrobial can treat the disease so we need broad spectrum antimicrobial agents. 3.

The possible clinical benefits of administrating antibiotics to help control periodontal disease must be weighed against possible adverse reactions, so for serious diseases the use of antimicrobial agents is very beneficial so we should give them to the patients like in TB, but in some diseases the patient may not get benefits more than the side effects so you should not give the patient antimicrobial in this case, like in chronic periodontitis. 4.

5. Common and indiscrement use of antibiotics worldwide has contributed to increasing

numbers of resistant bacterial strains over the last 15 to 20 years, due to continue wide use antibiotics for cases that don’t need antibiotics.

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The characteristics of ideal antibiotic for use in prevention and treatment of periodontal diseases: Specific for periodontal pathogens, but this can't be achieved in perio. Allogenic (doesn’t cause any allergy to the patient) and non toxic. Substantive, that means the drug is not absorbed but it is adsorbed (‫ليس امتصاص لكن ادمصاص‬) that means the drug will reside in the tissues without dissolving in the body fluids or the body structure, and when the concentration of the drug is reduced in that area it comes again and substitutes its reduced concentration, and this feature makes chlorhexidine very effective in perio treatment because it can reside on the oral mucosa up to 12 hours that’s why we use it twice daily. • Not in general use for treatment of other diseases and inexpensive. • • •

The Ideal antibiotics for treatment of periodontal diseases does not exist, because as we said not all the characteristics are achieved (not all the drugs are inexpensive, you can't find drug that only acts in the periodontal tissues without affecting the other parts of the body, etc...) No single antibiotic at concentration achieved in body fluids inhibits all putative periodontal pathogens, so sometimes we give combination of antibiotics because of the complexity of pathogens, although the combination could lead to more side effects but the disease is serious (aggressive periodontitis), it could lead to tooth loss or sometimes can cause systemic problems. Here the doctor punished us because our poor knowledge in the clinic, so study hard students!! Now look at the figure on the right side: This figure tells us about the treatment of the different types of periodontal diseases, if the person is healthy so he should go for supportive periodontal treatment (maintenance visits), but if he is diagnosed with one of destructive periodontal diseases like chronic periodontitis, aggressive periodontitis, chronic periodontitis as a manifestation of systemic disease you should treat him according to his disease.

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As you see in the figure if the disease is chronic periodontitis we should go for oral hygiene, debridement, supportive treatment, and sometimes surgical access for root debridment, but only antibiotic is indicated in cases where we have refractory sites (the inflammation didn’t resolve from the sites of treatment after you finished the treatment of the patient), after that if the disease didn’t resolve in this case the diagnosis could be wrong from the beginning (it is not chronic it could be aggressive or chronic as a manifestation of systemic disease) so it is very important to diagnose the disease properly to know how to treat the patient.(the doctor said continue the figure by your self).

Antibiotics: Here we will talk about specific types of antibiotics

Tetracyclines: Why these drugs are widely used although these are bacteriostatic? In tetracycline there are many good features but the most important feature is that this drug can achieve the highest concentration in the gingival crivicular fluid (GCF) (2 to 4µg/ml), unlike the amoxicillin that doesn’t exist in the GCF but only you can detect it in the serum. So in tetracycline the drug reaches the base of the pocket from the serum and from the GCF. Other features: They have the ability to inhibit the growth of Actinobacillus actinomycetumcomitans (Aa); this means that it is the drug of choice in the treatment of localized aggressive periodontitis. • They exert an anticollagenase effect that can inhibit tissue destruction, and we will talk about this later. • They may aid bone regeneration, and this is approved in some studies. •

The doctor asked about the concentration of tetracycline hydrochloride and unfortunately no one answered, and the doctor again punished us!! The answer is 250mg, and it is given 4 times daily

Clinical use: Again why tetracycline is the drug of choice as adjuncts in the treatment of localized aggressive perodontitis? Because it is very effective against Aa, and it is present in the GCF in high concentration. It is not advisable to engage with a long term regimens of tetracyclines because of the possible development of resistant bacterial strains. 4

Tetracyclines now tend to be replaced by more effective combination antibiotics, because we know that the complex bacterial pathogens of periodontal disease can't be eliminated only by a bacteriostatic drug. The less the times the patient take the drug the more the compliance, so the drug that is taken once daily is better than the drug that is taken 4 times daily, so in tetracyclines we prefer minocycline, and doxycycline.

Doxycycline: Characteristics 1. Same spectrum of activity as minocycline. 2. its concentration is 100mg 3. Patients may be more compliant with doxycycline, because it can be taken once

daily. Contraindications: The doctor said this is very important but he didn’t say any thing about it. But these are from the net: • Nausea • Diarrhea • Vomiting • Skin reaction to sunlight (photosensitivity) • Upset stomach (dyspepsia) • Loss of appetite • Unexplained rash • Difficulty swallowing (dysphagia). The doctor said that it is very important to know when to take the drug before or after meal, with or without milk, with or without falafel!! , but he didn’t say any thing. The doctor means the precautions, So these are the precautions as in the net: Doxycycline should not be administered together with milk, because it affects the absorption, and the concentration in the blood. • It should be taken on empty stomach 1 hour before or 2 hours after meals. • pregnancy • <8 years old • avoid sun/UV light exposure • caution if impaired renal fxn • caution if impaired liver fxn •

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• • •

caution if SLE caution if candidiasis predisposition caution in elderly pts

The regimen for the treatment of localized aggressive periodontitis is 100 mg twice daily for the first day, then once daily for 20 days (the total is 21 days).

Metronidazole: It is bactericidal broad spectrum and effective to anaerobic bacteria and all periodontal pathogens are anaerobic, but it is not effective alone for the treatment of aggressive periodontitis so we need combination of drugs to treat it. It is effective against anaerobes such as Porphyromonas gingivalis and Provetella intermedia Clinical use: 1. Acute necrotizing ulcerative gingivitis. 2. Chronic periodontitis refractory on sensitivity test. 3. Aggressive periodontitis (in combination with amoxicillin).

It has been used: • As a supplement to vigorous scaling and root planing, resulting in a significant reduced need for surgery • In combination with amoxicillin or amoxicillin - clavulanate potassium (Augmentin), by this combination it may be of value in the management of patients with localized aggressive periodontitis or refractory periodontitis Contraindication: 1. It is contraindicated with alcohol ingestion, because it can result in sever cramp,

nausea, and vomiting (this is called Disulfiram like reaction). 2. Patients undergoing anticoagulant therapy should

avoid metronidazole because it prolong prothrombin time. 3. It should be also avoided in patients who are taking lithium (sedative). Others from the net: • Liver disease. • A stomach or intestinal disease such as Crohn's

disease. 6

Disulfiram reaction: This is an unpleasant reaction due to the interaction of disulfiram and alcohol. It can cause symptoms such as flushing, throbbing in head and neck, throbbing headache, breathing difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitations, tachycardia, hypotension, syncope, uneasiness, weakness, vertigo, blurred vision and confusion.

• A blood cell disorder such as anemia (lack of red blood cells) or leukopenia (lack of

white blood cells). • Epilepsy or other seizure disorder. • Nerve disorders.

now look to the figure to the right: In the periodontal disease we have loss of attachment and what cause that loss are two things: 1. the bacteria and their irritants (slight role) 2. an inflammatory response from the host cells toward the bacterial irritants which lead to production of inflammatory mediators such as PGE2, IL and matrix metalloproteinase (MMP) That leads to the bone and connective tissue destruction, which means 70% of destruction is from the host defense and 30% of destruction is from the bacteria. When we do scaling and root planning we are eliminating the first one which is the bacteria, but some people thought about something that can inhibit the other effect which is the host response. This can be done by a drug that is called periostat.

Periostat: It is systemic doxycycline hyclate in a concentration that does not have an antimicrobial effect, and it only produce an anti-collagenase effect particularly that produced by polymorphonuclear leukocytes to inhibit the host response. It is available in 20mg but doxycycline that is antimicrobial it is 100mg, so periostat is less in concentration than doxycycline, and this make the drug away from developing resistance and away from developing side effects. It is used twice daily, for at least 9 months, and its effect will last up to 2 years.

The end 7

‫كلمات جميلة لبن القيم‬ ‫)نسأل ال أن يرفع فى الجنة درجته (‬

‫من كتاب "الداء و الدواء"‬

‫يقول الشيخ ‪:‬‬ ‫ال ‪-‬سبحانه وتعالىُ‪-‬‬ ‫يعّوض عن كل ما سواه‪ ,‬ولُ يعّوض منه شيء‪,‬‬ ‫وُ يغِني عن كل شيءولُ يغِني عنه شيء‪,‬‬ ‫وُ ِيجير من كل شيء ولُ ِيجير منه شيء‪,‬‬ ‫وَ يمنع من كل شيء‪ ,‬ولُ يمَنع منه شيء‪,‬‬ ‫فكيف يستغني العبد عن طاعة من هذا شأنه طرفة عين?!‬ ‫وكيف ينسى ذكره ويضيع أمره‬ ‫حتى ينسيه نفسه‪ ,‬فيخسرها ويظلمها أعظم الظلم?!‬ ‫فما ظلم العبد ربه ولكن ظلم نفسه‪,‬‬ ‫وما ظلمه ربه ولكن هو الذي ظلم نفسه!‪.‬‬ ‫وصلى الله وسلم وبارك على نبينا محمد وعلى آله وصحبه‬ ‫والتابعين‬ ‫إلى يوم الدين والحمد لله رب العالمين‬ ‫أستغفر الله الذى ل إله إل هو و أتوب إليه‬

‫‪Done by: Khalid Feery‬‬ ‫ل تنسونا من صالح دعائكم‪ ،‬وجزاكم ال كل خير‬

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