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antibiotics and periodontics in periodontal treatment.pptx
1.
2.
3.
4. Introduction
In the past, death from an incurable bacterial
infection was considered as a major issue.
With identification and development of various
classes of antimicrobial agents
as much as 30% or more of all the hospitalized
patients are treated with one or the other
antimicrobial therapy.
5. Antimicrobial agents are divided into
3 categories:
• Antibiotics.
• Antiseptics and
• Sulfonamides.
Addy M in 1986 has divided antimicrobial agents used in
periodontics into 2 groups:
• Preventive agents – that affect the development of
supragingival plaque.
• Therapeutic agent – that is directed against subgingival
plaque.
.
6. Antibiotics are substances produced by various
species of microorganisms (bacterial, fungi, and
actinomycetes) that suppress the growth of or kill
other microorganisms at very low concentration.
This definition excludes other natural substances
which also inhibit microorganisms but are produced
by higher forms (e.g. antibodies) or even those
produced by microbes but are needed in higher
concentrations (ethanol, lactic acid, H2O2).
7. Antiseptic - chemical antimicrobial agent
applied topically or subgingivally to mucous
membranes, wounds, or intact dermal
surfaces to destroy microorganisms and
inhibit their reproduction or metabolism.
Disinfectants, a subcategory or antiseptics,
are anti microbial agents that are generally
applied to inanimate surfaces to destroy
microorganisms.
8. Minimal Inhibitory Concentration (MIC) -The
lowest concentration of the agent that prevents
the visible growth of microorganisms after 18-24
hrs of incubation.
Minimal Bactericidal Concentration (MBC) - The
lowest concentration that results in 99.9% decline in
bacterial numbers.
Drug resistance: It refers to unresponsiveness of a
microorganism to an antimicrobial agent.
Natural or Acquired
9. • Natural resistance is generally a group or
species characteristic
E.g., gram negative bacilli are unaffected by
penicillin.
• Acquired resistance can happen with any
microbe. (which was sensitive before) This
occurs due to the use of an antimicrobial
agent over a period of time.
Resistance may be developed by mutation
or gene transfer .
10. Resistant organism can be
• Drug tolerant due to loss of affinity of the target biomolecule of
the microorganism for a particular antimicrobial agent or due to
acquisition of an alternative metabolic pathway.
• Drug destroying due to elaboration of enzyme by the resistant
microbe which inactivates the drug.
E.g., β-lactamases produced by staphylococci, haemophilus,
gonococci etc. which inactivate penicillin G.
Cross resistance - Acquisition of resistance to one antimicrobial
agent conferring resistance to another antimicrobial agent, to
which the organism has not been exposed. This is more
commonly seen in mechanistically related drugs.
E.g. resistance to one tetracycline means insensitivity to all
others.
11.
12. synergy n., combined action or functioning;
synergism. the interaction of elements that when
combined produce a total effect that is greater than
the sum of the individual elements.
13. Drug synergism (Greek: Syn –
together; ergon – work)
When the effect of one drug is facilitated or increased by the other,
they are said to be synergistic.
In a synergistic pair, both the drugs can have action in the
same direction or when given alone it may be inactive but
when given together enhance the action of the other.
• Additive: When the effects of the two drugs are in the same
direction and simply add up.
E.g. Aspirin + paracetamol combination.
• Supraadditive (potentiation): The effect of combination is
greater than the individual effects of the components.
E.g. Sulfonamide + trimethoprim.
(1+1=3)
15. The phenomena of opposing actions of two drugs
acting on a same physiologic system is termed as
drug antagonism.
Eg; morphine and naloxane
acetylcholine and atropine
16. History of antibiotics
The term antibiotic (from greek;anti-against, bios-
life)
Coined by Selman Waksman(1942)
18. Originally they were known by the name
‘ANTIBIOSIS’ -- VUILLMEN
The first man made antibiotic –
‘salvarsan’ - Dr.Ehrlich
The first commercially available anti bacterial
antibiotic is ‘prontosil ‘ (a sulphanomide)—
Garhard Domagk
22. Classification of antibiotics
On the basis of structure
On type of action
Based on bacterial spectra
Based on mode of action
23. On the basis of structure
• Those which contain beta lactam ring nucleus
• Eg;pencillins,cephalosporins,cephalomycins
Beta-lactams
• These are either derived from various species of streptomyces fungi
and end in mycin
• Eg;streptomycin,tobramycin,gentamicin, amikacin
Aminoglycosides
• Names of this group contain sulpha /sulfa group
sulphonamides
• They all have a 4-ringed structure and their names end
in cycline eg;doxycyline,
Tetracyclines
• These all contain azole ring and their names end in
azole.eg;metronidazole
Azoles
• These are all structurally related to nalidixic acid and
most in ‘oxacin’ eg; coproflaxacin
Quinolones
• Named because of presence of a large lactone ring
erythromycin
Macro lides
• Chloramphenicol,clindamycin, and vancomycin
Others
25. Based on mechanism of action
• Agents that inhibits synthesis of bacterial cell walls:
E.g. Penicillins, cephalosporins. Basitracin, vancomycin,cycloserine
• Agents that act directly on the cell wall membrane of microorganisms,
affecting permeability and leading to leakage of intracellular components, by
binding to cell wall sterols.
E.g. nystatin and amphotericin-B.
• Agents that affect the function of 30s and 50s ribosomal subunits
to cause a reversible inhibition of protein synthesis (bacteriostatic
drugs)
•
E.g. Chloramphenicol, tetracyclines and Clindamycin.
• Agents that bind to 30s ribosomal subunit and alter protein
synthesis leading to cell death.
E.g. Aminoglycosides.
26. • Agents that affect bacterial nucleic acid metabolism.
E.g. Rifampin inhibits RNA polymerase, Quinolones inhibit topo isomerases,
ethambutol
• Anti-metabolites, these blocks the essential enzymes of folate
metabolism.
E.g. Trimethoprim and sulfonamides.
• Antiviral drugs:
Nucleic acid analogs. E.g. acyclovir that selectively inhibits viral DNA
polymerase, Zidovudine inhibits reverse transcriptase.
Non nucleoside reverse transcriptase inhibitors. E.g. Nevirapine.
Inhibitors of other essential enzymes. E.g. Inhibitors of HIV protease
27.
28.
29. Based on Spectrum of activity
• Narrow (limited/specific) spectrum.
• Broad spectrum (effective against variety of
micro-organisms).
30. Narrow spectrum………….
Antibiotics effective against gram positive bacteria
; Pencillin, macrolides, novobiocin and fucidin
Antibiotics effective against gram negative bacteria
eg; Streptomycin and other aminoglycosides, paramomycin
Antibiotics effective against both gram positive
and negative bacteria eg; ampicillin, amoxicillin,
cephalosporins, imjepenam, rifamycin
Against acid fast bacilli
eg; streptomycin, rifampicin, viomycin, capreomycin and
kannamycin
36. List of antibiotics commonly used in
peridontics for various purposes
Pencillins
Tetracyclines
Metranidazoles
Erythromycin
Clindamycin
Rarely flouro quinalones-oflaxicin
37. Role of antibiotics in periodontics
• Today, periodontitis has classified in a group of
• infectious diseases called ‘Biofilm Diseases’.
• A biofilm is a complex bacterial structure adherent to
wet surfaces.
• Biofilm protects the bacteria from the immune system
of the host as well as from antimicrobial agents.
• Hence, a biofilm is a difficult therapeutic target.
• In the field of periodontal microbiology, It is
demonstrated that, several antibiotics need to be
much higher concentrated to reach the minimal
inhibitory concentration (MIC) in a biofilm.
• Biofilm-grown cells are 1,000–1,500 times more
resistant to antibiotics than planktonic-grown cells.
38. Several theories have been put forward
to explain the increased resistance in
bacterial biofilm.
• One theory suggests antimicrobial agents cannot penetrate, or infiltrate, the
depths of a mature biofilm. hence adequate inhibitory concentrations never
reach the bacterial microcolonies.
• Scanning electron microscopy and laser cone focal
microscopy reveal channels within the microstructure of the biofilm
through which nutrients reach bacterial cells.
• Antibiotics has small molecular size, hence diffuses through such channels.
But many antibiotics carry a positive charge and are rather hydrophilic in
nature hence adheres to extracellular material of biofilm matrix,
the glycocalyx.
• Once bound, the antibiotic is unlikely to penetrate the innermost constituents
of the biofilm, decreasing the effectiveness of the antibiotic and ⁄or rendering it
inactive.
39. • An alternative theory proposes that susceptible bacteria
may be protected by other resistant bacteria or their products.
E.g. β-lactamase, a bacterial enzyme that hydrolyzes the β-lactam
ring in the penicillin molecule and destroys antimicrobial activity.
• High β-lactamase levels have been observed within periodontal
pockets. These increased enzyme protects both the β-lactamase-
producing and the non β-lactamase producing microorganisms from
penicillin.
• Other theory proposed that ‘persister cells’ exist in
the biofilm express a phenotype involving the expression of genes or
genotypes that are not required for survival in the nutrient-rich
environment
40. Indications for use of antibiotics
in Periodontics:
• Periodontal patients who do not respond to
conventional mechanical therapy.
• Patients with acute periodontal infections
associated with systemic manifestations.
• For prophylaxis in medically compromised
patients.
• As an adjunct to surgical and non-surgical
periodontal therapy.
41. Ways of administering of
antibiotics
• As a prophylaxis
• Systemically
• Local/topical
43. Are …….
To reduce the risk of metastatic infection
where bacteria are transported through the
blood stream to other parts of body, resulting
in infection.
Eg;sabe,rhd,phv
Secondly,if there is an increased infection risk
due to impaired host resistance.
Eg;pts treated with cancer chemotherapy,
diabetics, pts treated with immuno suppresive
drugs, during insertion implants and bone
grafting procedures
44. Metastatic infections
All dental procedures which induced bleeding
will usually be followed by a transient
bacteremia, which really persists more than
15min
Accordingly, bacteremias of dental origin
have been suggested as sources of metastatic
infection among patient with diabetes, kidney
disease, prosthetic joint replacement and
splenectomy
46. Best documented indication for antibacterial
prophylaxis in conjunction with dental procedure
include cardiac condition like…..
Endocarditis
Micro-org most commonly involved
streptococci, staphylococci, enterococci
47. • PROPHYLACTIC REGIMENS FOR DENTAL,ORAL,RESPIRATORY
TRACT,OR OESOPHAGEAL PROCEDURES
• SITUATION AGENT REGIMEN
• 1)Standard general AMOXICILLIN Adults:2g;children:50mg/kg
• Prophylaxis orally 1hr before the procedure.
•
• 2)Unable to take oral AMPICILLIN Adults:2g,IM or IV;ChildrenL:50mg/kg IM
• Medications OR IV within 30 min before procedure.
•
•
• CLINDAMYCIN Adults:600mg;children:20mg/kg orally
• 1hr before the procedure 3)Allergic to
3)allergic to penicillin OR
• CEPHALEXIN OR Adults:2g;children:50mg/kg orally 1hr
• CEFADROXIL before the procedure
• OR
• AZITHROMYCIN OR Adults:500mg;children:15mg/kg orally 1hr
• CLARITHROMYCIN before the procedure.
•
• 4)Allergic to penicillin CLINDAMYCIN Adults:600mg;children 20mg/kg IV within
• and unable to take oral OR 30 min before the procedure.
• Medications CEPHAZOLIN Adults:1g;children:25mg/kg IM or IV
• Within 30 min before procedure.
• Total child dose should not exceed adult dose.
• Cephalosporins should not be used in individuals with immediate type hypersensitivity reaction
(urticaria,angioedema,or anaphylaxis to penicillins)
48. Systemic administration of
antibiotics:
Bacteria can invade periodontal tissue, making
mechanical therapy alone ineffective. Hence Systemic
administration of antibiotics is necessary adjunct in
controlling bacterial infection.
Prime candidates for systemic antibiotic therapy
are
49. Indication for syst administra…
1)Patients Recurrent or refractory periodontitis.
2) Patients with aggressive types of periodontitis
Or with medical conditions predisposing to
periodontitis.
3)Patients with acute or sever periodontal
infections (periodontal abscess, acute
necrotizing gingivitis/periodontitis).
1)Patients with chronic periodontitis may also
benefit from antibiotics?
50. Systemic use of antibiotics in
periodontal therapy
• This topic arises several questions like……
How useful are systemically administered antimicrobial agents in the
treatment of periodontal disease ?
Do we recognize key pathogens and should we try to eradicate them?
Can such organisms be reached and killed by anti microbial agents via
systemic route?
What is the benefit of a systemically adminstered drug in addition to or
instead of mechanical treatment?
Which are the limitations and unwanted effects of this form of therapy?
51. How useful………
Systemic drug therapy offers several
benefits over local drug delivery.
• Firstly, the wide delivery of drug to intraoral
tissue via serum, they may be more practical for a
patient with multiple diseased sites.
• Secondly it affects the periodontal pathogens
colonizing oral mucosa or are present in the saliva,
and reduces the risk for subgingival
recolonization of pathogens after periodontal
therapy may be reduced.
52. Do we recognize
• Once the decision is been made for the use of an
antibiotics, the Subgingival samples can be collected
with sterile paper points or a curette. Sent for :
• Microbiological analysis.
• Antimicrobial sensitivity testing.
• Bacteria can invade periodontal tissue, making
mechanical therapy alone ineffective. Hence
Systemic administration of antibiotics is
necessary adjunct in controlling bacterial
infection.
53. Can such organisms be reached
• certain patients do not respond favorably to
mechanical therapy like
• Because:
• Sites with deep periodontal pockets, grooves, furcations,
and
concavities are difficult to access with periodontal
instruments. periodontopathic bacteria remains in such
sites.
• Periodontal bacteria have been detected on the mucosa,
tongue, and gingiva, from where they colonize dental
plaque.
• P.g, A.a, and spirochetes invade gingival epithelial cells,
connective tissues and dentinal tubules.
54.
55. The disadvantages of systemic
antibiotic therapy:
• The inability of systemic drugs to achieve high
GCF concentration.
• Increased risk of adverse drug reactions (E.g. Drug
exanthema/rashes etc)
• Increased selection of multiple antibiotic resistant
microorganisms.
• Unwanted effects on extra oral bacteria (E.g. Enteric
flora).leading to superinfections.
• Uncertain patient compliance.
56.
57.
58. Tetracyclines:
The most widely prescribed adjunctive agents for periodontal
therapy.
Broad-spectrum antibiotics.
Seven basic types are currently in use. They are chemically similar
and they possess similar antibacterial spectra.
The first tetracyclines developed were –
Chlortetracycline, Oxytetracycline, Tetracycline and
Demaclocycline. The next groups of tetracyclines developed were –
Doxycycline, Methacycline and Minocycline.
Tetracyclines have the ability to concentrate in the periodontal
tissues and inhibit the growth of Actinobacillus
actinomycetemcomitans.
In addition, they exert an anticollagenase effect that can inhibit tissue
destruction and may aid bone regeneration (Host Modulation).
59. Pharmacology
• The tetracyclines are a group of antibiotics
produced naturally from certain soil micro-
organisms (species of Streptomyces) or
derived semi-synthetically.
• These are effective in treating periodontal
diseases because their concentration in the
gingival crevice is 2 to 10 times higher then
in serum.
• Tetracyclines at a low gingival crevicular
fluid concentration (2 to 4 µg/ml) are very
effective against many periodontal
pathogens.
60. Mechanism of action
• Tetracyclines bind to the bacterial 30S ribosomal
subunit and inhibit protein synthesis in the bacterial
cell-bacteriostatic antibiotics.
• However, at high concentrations, as achieved with
localized delivery of the antibiotic directly into the
periodontal pocket, the tetracyclines may exert a
bactericidal effect.
Clinical Use
Patients at high risk for periodontal breakdown including
aggressive periodontitis (localized and generalized juvenile
periodontitis, rapidly progressive periodontitis) and
refractory periodontitis.
• Debridement and even surgery have failed to eliminate
A.a from LJP infection, indicating that chemotherapy
necessary to eradicate A.a completely from the subgingival
areas.
61.
62. • Resistance to the tetracyclines is
relatively common.
• Mediated by a number of genetic determinants located
on plasmids or on the bacterial chromosome.
• Resistance occur due to the coding of an efflux pump
that actively removes the drug from bacterial cell, hence
sufficient drug concentration is never achieved.
• This mechanism of resistance occurs to a lesser extent
to doxycycline.
• Another mode is referred to as ‘Ribosome protection’.
Here tetracyclines are prevented from binding to the 30S
ribosomal subunit.
• This mechanism generally conveys resistance equally to
all tetracyclines. Hence Tetracyclines are now replaced by
more effective combination antibiotics.
63. Adverse effects
Nausea, vomiting and diarrhea.
Photosensitivity
Enamel hypoplasia
They are potential teratogens, do not use in pregnant females
(causes fetal tooth-staining).
64. Contraindications:
•In children during tooth development (less than 8 yrs old) may result in
permanent discoloration of teeth.
•Contraindicated during pregnancy and lactation.
•Oral contraceptives becomes less effective.
•May depress serum prothrombin activity in patients receiving concurrent
anticoagulant therapy.
65. Minocycline:
•Broad spectrum antibiotic.
•In patients with adult periodontitis, it suppresses spirochetes
and motile rods as effectively as scaling and root planing,
suppression remaining evident for up to 3 months after therapy
•Given twice a day(100-200mg/day for 7days), facilitating
compliance.
•Associated with less photo and renal toxicity than tetracycline,
may cause reversible vertigo
66. Doxycycline:
• Broad spectrum antibiotic
• Given once daily (100 mg twice daily the first day, then 100 mg
once daily). More compliance. To reduce gastrointestinal upset
50 mg can be taken twice daily.
• The absorption from the gastrointestinal tract is not altered by
calcium, metal ions, or antacids, as is absorption of other
tetracyclines.
• Used as a subantimicrobial dose (20-mg dose twice daily) to
inhibit collagenase.
• Doxycycline and minocycline may be given safely to patients
with renal dysfunction (unlike tetracycline which is
eliminated unchanged by glomerular filtration).
67. Host modulation:
• Doxycycline Hyclate (Periostat)
• Periostat, available as a 20-mg capsule of doxycycline hyclate,
prescribed twice daily.
• Mechanism of action is by suppression of the activity of
collagenase, particularly that produced by polymorphonuclear
leukocytes.
• It does not have antibacterial effects because the dose is too low to
affect bacteria. Hence resistance to this medication has not been
seen.
• The colonization or overgrowth of the periodontal pocket by
bacteria resistant to doxycycline, tetracycline, minocycline,
amoxicillin, erythromycin, or clindamycin has not been
observed.
• No evidence of acquisition of multiantibiotic resistance was
found.
68. METRONIDAZOLE:
Nitroimidazole compound. Bactericidal to anaerobic
organisms (Porphyromonas gingivalis and Prevotella intermedia).
The cytotoxic metabolites of metronidazole directly interact
with bacterial DNA, and possibly other macromolecules,
resulting in cell death.
69. Clinical Use
Metronidazole is not the drug of choice to treat A.actinomycetem
comitans infections. But it may be effective at therapeutic levels
owing to its hydroxy metabolite. And when used in
combination with other antibiotics.
Used clinically to treat gingivitis, ANUG, chronic periodontitis,
aggressive periodontitis, and Refractory periodontitis.
A single dose of metronidazole (250 mg orally) appears in both
serum and gingival fluid in sufficient quantity to inhibit
periodontal pathogens.
70. Metronidazole and its hydroxyl-metabolite act synergistically
with amoxicillin.
Metronidazole covers most anaerobes and amoxicillin most
aerobic bacteria. Hence useful in many mixed periodontal
infections.
Commonly prescribed regimen is 250 mg t.i.d for 7 days.only
Contraindications:
• Alcohol ingestion, since abdominal distress, nausea, vomiting
and / or headache may occur (an antabuse effect).
• Pregnant women and nursing mothers. (tumorigenicity in some
animals)
• Patients receiving anticoagulants, lithium or disulfuran (an anti-
abuse drug)
71. Penicillins
The most widely used antibiotics.
Broad class of antibiotics. Commercially available since 1940.
Drugs of choice in treatment of many serious infections.
Earlier Penicillins used to prevent plaque formation and caries.
However in late 1950’s, research work showed that daily use of
penicillin leads to development of resistant strains and
hypersensitivity reactions (DCNA 1988).
Pharmacology:
• Inhibits bacterial cell wall production, hence bactericidal..
72. Chemical structure:
• Substitutions on the acyl side chain yielded wide variety of
penicillin compounds with different properties.
• i.e., improved stability to gastric acid, improved absorption
and higher serum concentrations, and active against gram-
negative as well as gram-positive bacteria.
74. Amoxicillin:
Semisynthetic penicillin.
Effective against both gram-negative and grampositive bacteria
(broad spectrum)
Absorbed well on oral administration and penetrates into the
gingival crevicular fluid.
Is highly susceptible to bacterial β-lactamases.
β- Lactamase is an enzyme produced by a number of different
bacteria which hydrolyzes the b-lactam ring. Thus destroying
antimicrobial activity of the penicillin.
As a result, use of amoxicillin alone as an adjunct to periodontal
therapy has been limited.
Augmentin (amoxicillin-Clavulanic acid) may be useful in the
management of patients with refractory or localized aggressive
periodontitis.
75. Clavulanic acid exhibits no antimicrobial activity. β-lactamase
enzymes have a greater affinity for clavulanic acid than for
amoxicillin, hence binds to the clavulanate moiety.
Bacteria resistant to amoxicillin may become susceptible to the
combination of amoxicillin and clavulanic acid.
The efficacy of Augmentin has been tested in a few clinical trials
with conflicting results.
76. Side Effects:
• Allergic hypersensitivity- Most common adverse reaction.
• Anaphylaxis – 1/10000 patients (Angioedema).
10% mortality rate.
Anaphylaxis possible after negative skin testing.
• Rashes -common reaction. 50% do not have a recurrent rash.
• Exposure to any of the penicillins precipitates an allergic
reaction in a susceptible individual.
77.
78. Cephalosporin
• Its the family of β-lactams, similar in action and structure to
Penicillins.
• They are frequently used in medicine and are resistant to a
number of β-lactamases.
• Clinical Use:
• Cephalosporins are generally not used to treat dental-related
infections.
• The penicillins are superior to cephalosporins in their range
of action against periodontopathic bacteria.
• Side Effects:
• Patients allergic to Penicillins must be considered allergic to
all ß-lactam products. Rashes, urticaria, fever, and
gastrointestinal upset have been associated with
cephalosporins.
79. Clindamycin
• Clindamycin is bacteriostatic
• Inhibits bacterial protein synthesis, by binding irreversibly
to 50S ribosomal subunit.
• The drug is active against most gram-positive bacteria,
including both facultative and anaerobic species.
• It is active against gram negative anaerobes. particularly
associated with the periodontal flora.
• Eikenella corrodens, a suspected periodontal pathogen, is
inherently resistant to clindamycin. A. actinomycetemcomitans
also demonstrates in vitro resistance to this antibiotic.
• Effective in situations where patient is allergic to penicillin.
80. Clinical studies
• Walker and co-workers (1993) have shown aid in stabilizing
refractory patients. Dose used was 150 mg q.i.d for 10 days.
• Jorgensen and Slots J (2000) have recommended a regimen
of 300 mg twice daily for 8 days.
• These studies suggest clindamycin-HCL may be a useful
adjunct in the treatment of truly refractory patients.
• Clindamycin has also shown efficacy in patients with
periodontitis refractory to tetracycline therapy.
81. Side Effects
Associated with pseudomembranous colitis more often than other
antibiotics, thereby limiting its use. (can be used with caution)
Watery diarrhea, fever, leucocytosis and crampy abdominal pain
beginning on 4th to 9th day of antibiotic therapy suggestive of
pseudomembranous colitis.
The cause is due to the release of enterotoxin by clostridium
difficile that interact with the cells lining the lower GIT, causing
cell necrosis and decreased water and electrolyte absorption
producing diarrhea.
82. Most common Less frequent Rare
Ampicillin
Cephalosporins
Clindamycin
Amoxicillin
Cloxacillin
Erythromycin
Penicillin G
Penicillin K
Aminoglycoside
Metronidazole
Tetracyclines
Antibiotics commonly used in dentistry that are
associated with pseudomembranous colitis
Treatment:
Antibiotics should be discontinued, rehydrate the patient and
replace the lost electrolytes.
Life threatening cases can be treated with oral Vancomycin.
83. Ciprofloxacin
• Fluoroquinolone.
• Active against gram-negative rods, including all facultative and
some anaerobic putative periodontal pathogens.
• Inhibits DNA gyrase, causing permanent DNA cleavage.
• Clinical Use:
• It demonstrates minimal effect on Streptococcus species
(associated with periodontal health), hence ciprofloxacin
therapy may facilitate the establishment of a healthy
microflora.
• It is the only antibiotic in periodontal therapy to which all
strains of A actinomycetemcomitans are susceptible.
• It also has been used in combination with metronidazole.
84. Side Effects:
• Nausea, headache, and abdominal discomfort -common side
effects.
• It inhibits the metabolism of theophylline, and caffeine and
concurrent administration can produce toxicity.
• Quinolones have also been reported to enhance the effect of
warfarin and other anticoagulants.
• It should not be used in patients who are under 18 years of
age (arthralgia). Animal studies show joint/cartilage damage
in weight bearing joints of young animals.
85. Macrolides
Contains many-membered lactone ring to which one or more
deoxy-sugars are attached.
Irreversibly binds to the 50 S ribosomal subunits.
They can be bacteriostatic or bactericidal, depends on concentration
of the drug and the nature of the microorganism.
Clinical Use
Erythromycin does not concentrate in GCF, and not effective
against most putative periodontal pathogens. Hence not
recommended in periodontal therapy.
86. Spiramycin :
• Active against gram-positive organisms.
• Excreted in high concentrations in saliva.
• Several studies have shown benefits in advanced periodontal disease, as
measured by the Gingival Index, the Plaque Index, pocket depth, and
crevicular fluid flows.
• It is a safe, nontoxic drug with few and infrequent side effects
Azithromycin:
• Azalide class of macrolides.
• It is effective against anaerobes and gram-negative bacilli (all serotypes of A.
actinomycetemcomitans and P. gingivalis).
• Dose -500 mg once daily for three consecutive days. significant levels of azithromycin
can be
detected in most tissues for 7 to 10 days.
87. The concentration in periodontal lesions is significantly higher than
that of normal gingiva.
It has been proposed that azithromycin penetrates fibroblasts and
phagocytes in concentrations 100 to 200 times greater than that of
the extracellular compartment.
The azithromycin is actively transported to sites of inflammation by
phagocytes and then released directly into the sites of inflammation.
Clinical study:
• Smith et al. (2002) conducted a double-blind, placebo-controlled
clinical trial to evaluate the efficacy of azithromycin as an adjunct to
SRP.
• Azithromycin (500 mg ⁄day for 3 days)
• Clinical assessments were made at baseline and at 1, 2, 3, 6, 10, and
22 weeks post-SRP.
88. • After 22 weeks the azithromycin group showed improvement in
pocket probing depth and had fewer sites that bled on probing.
Deeper sites tended to show the greatest improvement.
• Spirochete levels were significantly lower throughout the study for
subjects who received azithromycin
Side effects
• The drug is relatively nontoxic
• Few adverse side-effects. These are nausea, vomiting, abdominal
pain or cramping, and diarrhea.
• Azithromycin is excreted in human breast milk, hence
contraindicated in nursing mothers.
89. Clinical studies: combination therapy
Rams and Slots (1992) reviewed combination therapy using systemic
metronidazole along with amoxicillin, Augmentin, or ciprofloxacin.
• The metronidazole-amoxicillin and metronidazole-Augmentin
combinations provided excellent elimination of many organisms in
adult and localized aggressive periodontitis.
• These drugs have an additive effect regarding suppression of
A.actinomycetemcomitans.
Tinoco and coworkers (1998) found metronidazole and amoxicillin to
be clinically effective in localized aggressive periodontitis, although
50% of patients harbored A. actinomycetemcomitans one year later.
• Metronidazole-ciprofloxacin combination is effective against A.a.
Metronidazole targets obligate anaerobes, and ciprofloxacin targets
facultative anaerobes.
• This is a powerful combination against mixed infections.
92. Treatment Authors Average probing depth reduction in mm
Repeated scaling and root planing Magnusson et al. (1984)18 2.3
Repeated scaling and root planing Listgarten et al. (1978)19 2.2
Tetracycline fibers + scaling and root planing Newman et al. (1994)16 1.8
Metronidazole gel + scaling and root planing Stelzel & Flores-de-Jacoby (1996)20 1.3
Minocycline gel + scaling and root planing Timmerman et al. (1996)21 2.3
Minocycline microcapsules + scaling and root planing Yeom et al. (1997)13 1.6
Minocycline ointment + scaling and root planing Van Steenberghe et al. (1999)22 1.9
Minocycline microspheres + scaling and root planing Williams et al (2001)23 1.3
Doxycycline gel (monotherapy) Garrett et al. (2000)24 1.3
Table 3. Reduction of probing depth in 4-7 mm pockets following periodontal therapy a
93. Combination therapy with two or more
antibiotics is used in special cases:
To prevent the emergence of resistant strains
To treat emergency cases during the period when
an etiological diagnosis is still in progress
To take advantage of antibiotic synergism.
Antibiotic synergism occurs when the effects of a
combination of antibiotics is greater than the sum
of the effects of the individual antibiotics.
Antibiotic antagonism occurs when one antibiotic,
usually the one with the least effect, interferes
with the effects of another antibiotic.
94. Antibiotic Adult dosage
Metronidazole 500 mg/t.i.d/8 days
Clindamycin 300 mg/t.i.d/8 days
Doxycycline or Minocycline 100-200 mg/q.d/7 days
Ciprofloxacin 500 mg/b.i.d/8 days
Azithromycin 500 mg q.d/4-7 days
Metronidazole +Amoxicillin 250 mg/t.i.d/8 days each drug
Metronidazole + Ciprofloxacin 500 mg/b.i.d/8 days each drug
Common Antibiotic Therapies in the Treatment
of Periodontitis
@ Systemic antibiotics in periodontics (Position paper), J Periodontol 2004;
75: 1553-1565.
95. Antibiotics and chronic periodontitis
• Studies have failed to establish conclusive
benefit of adjunctive antibiotics
– microbiota is poorly defined
– disease progression varies
– recolonisation occurs
• Studies have not shown certainty to enhance
long term outcomes
• Available data are fairly weak
• Systemic antibiotics cannot be indicated as
adjuncts for chronic periodontitis
96. • Slots J, Ting M. Systemic antibiotics in the
treatment of periodontal disease. Periodontol
2000 2002;28:106-76
• Herrera D, Sanz M, Jepsen S, Needleman I, Roldan
S. J Clin Periodontol 2002;29 Suppl 3:136-159.
• Walker C, Karpinia K. J Periodontol 2002;73:1188-
96
• Slots J. Position paper of the American Academy
of Periodontology. J Periodontol 1996;67:831-838
97. Aggressive periodontitis
• 250mg of tetracycline hcl-q.i.d-14 days+local
mechanical therapy
• If surgery indicated syst.tetracycline taken 1 hr
before surgery
• Doxycycline(100mg/day can be used instead of
tetracyclines + chlorhexidine rinses
continued for several weeks
• A combination of
amoxicillin+metronidazole(25omg+200mg t.i.d-7
days)used in case of unresponsiveness to
tetracyclines
101. ANUG
• Amoxicillin(500mg q.i.d-10 days) or
• Erythromycin(500mg q.i.d) or
• Metronidazole (500mg b.i.d-7 days) only in
case of severe anug (or)
200mg t.i.d for 7 days
102.
103.
104.
105. Biofilm
A biofilm is a complex bacterial
structure adherent to wet
surfaces.
Biofilm protects the bacteria from
the immune system of the host as
well as from antimicrobial agents.
Hence, a biofilm is a difficult
therapeutic target.
In the field of periodontal
microbiology, It is demonstrated
that, several antibiotics need to be
much higher concentrated to reach
the minimal inhibitory
concentration (MIC) in a biofilm.
Biofilm-grown cells are 1,000–1,500
times more resistant to antibiotics
than planktonic-grown cells.
106. LOCAL DRUG DELIVERY
Historical perspective:
W.D.Miller – 1880’s suggested Listerine as antimicrobial mouth rinse.
Macalpine etal 1985 – CHX irrigation.
Goodson 1979 – used hollow dialysis tubes filled with Tetracycline.
Goodson 1983 – Ethylene vinyl acetate polymer fiber (25% Tetracycline).
Noguchi etal 1984 - Hydroxypropylcellulose based films containing
tetracyclines
107. Brain & Strahan, 1978 - CHX based gels &
Friedman & Golumb,1982 – CHX films
Addy & Langeroudi, 1984 – Metronidazole administered self curing methyl
acrylate strips.
Elkayam, 1988 - Minocycline films.
Jones et al, 1994 – Minocycline microspheres.
Goodson, 1994 - Tetracycline fibers.
Taner et al, 1994 – Resorbable membrane strips with hydroxry- methyl
cellulose & 40% Doxycycline.
Polson et al 1997 – 10% Doxycycline.
108. Goodson and co workers (1979). – first to test the
feasibility of controlled delivery of antimicrobials
in periodontal pocket using Permeable hollow
cellulose acetate fibers filled with 20%solution of
tetracycline.
109. Questions of local drug delivery
What are best drugs ?
What are best delivery systems ?
How often apply drugs ?
What is the duration of results ?
Which disease can be treated ?
Is LOCAL ANTIBIOTIC THERAPY an adjunct are alternate to SRP ?
Any antibiotic resistant bacteria ?
Is local as effective as systemic delivery ?
110. Local application aims at three targets:
• Support of non-surgical mechanical anti-
infective therapy.
• Support of re-instrumentation during
supportive periodontal therapy.
• As alternative to subgingival re-
instrumentation during supportive periodontal
therapy.
111. Principles of local intra pocket delivery of antibacterial drugs
: (Aubrey Soskolnew, 1997)
GCF is easily accessible for insertion of delivery
device.
GCF provides leaching medium for release of drug
and for its distribution.
Periodontal diseases are localized to immediate
environment of the pocket.
112. Local Drug Delivery
Professionally applied Personally applied
1. Degradable
2. Non-degradable
Sustained release controlled
release
Irrigation and tooth pastes
113. Irrigation With Antibiotics
5% tetracycline (50 mg/ml) exhibited significantly greater antimicrobial
activity than either 0.12% CHX digluconate for 12 days or saline for 16
days
10% tetracycline-HCl- long periods of time (5 minutes)
in significantly greater attachment gain as compared to SRP alone over
at least a 6-month period of healing
0.5% metronidazole. Linden and Newman
114. Ideal Requirements Of Local Drug
Delivery Device:
1. Must be able to deliver the drug upto base of pocket.
2. Deliver the drug at Min. Inhibitory Conc.
3. Should retain after placement & should be
biodegradable.
4. Free from undesirable side effects.
5. Substantivity.
6. Therapeutically effective.
7. Cost effective.
8. Should be easily placed.
115. Advantages of LDD:
Action is site specific.
Decreased drug dosage with greater therapeutic concentration in
subgingival site (100 fold).
Decrease systemic side effects.
Risk of developing drug resistant microbial species is reduced.
No alteration of the protective microflora (Super infection).
Can maintain effective drug concentration in periodontal pocket for
sufficient time.
No problem of missing dose and reduce patience compliance problem.
116. Limitations:
Pockets ≥ 7mm cannot be treated effectively.
Furcation areas and inaccessible areas cannot be dealt with
antimicrobial agent.
Non- sustained local delivery is limited by only brief exposure.
Pathogens in other pockets & extra pocket oral surfaces do not get
affected.
Many visits required for drug application.
No effect on bacterial reservoirs.
Relatively costly.
117. Local vs Systemic
More concentration
Fewer side effects
Sustained delivery
Patient complaince
No significant
antibiotic resistance
Low chance of super
infection
Less expensive
Less chair side time
Effect on bacterial
reservoir also
Less no: of
appointments
Treats all the sites
118. Commercially available LDD systems
Actisite fibre Tetracycline Non resorbable
Atridox Doxycycline Biodegradable
Atrigel Doxycycline Biodegradable
Arestin /Periocline Minocycline biodegradable
Elyzol Metro gel Supplied in syringe
119. Tetracyclines:
Tetracycline and derivatives have been most
extensively used in the treatment of
Periodontitis since 1970’s.
Duggar 1948
Chlortetracycline – first
Tetracyclines for periodontal diseases:
Tetracycline HCl, Minocycline & Doxycycline
120. Tetracycline-ContainingFibers (Actisite)
The first local delivery product.
Ethylene/vinyl acetate copolymer fiber, diameter
0.5 mm, containing tetracycline, 12.7 mg/9
inches.
• Sustains tetracycline concentrations for 10 days
exceeding 1300 µg/ml.
• well beyond the 32 to 64 µg/ml required to inhibit
the growth of periodontal pathogens.
121. MIC levels:
• P. gingivalis: 0.06 μg/ml
• P. intermedia: 0.25 μg/ml
• Actinomycetemcomitans: 2μg/ml
On systemic tetracycline administration (250 mg four times daily
for 10 days, total oral dose, 10 g). GCF concentrations reported is
only 4 to 8 µg/ml.
In a 2-month study, compared with scaling and root planing, the
fibers used alone have provided more than a 60% greater
improvement in probing depth and clinical attachment level than
scaling alone. (Goodson JM and Tanner A, 1992)
124. • Site selection- 5mm or more
• Fibre preparation- length needed, number ot teeth, sterility
• Steps in placement -anaestesia, isolation, fibre
placement, place adhesive dressing.
• Patient instruction - accidental removal, rinsing, if fibre
lost
• Fibre removal- mouth rinse, isolate, tease the fibre with
currete, examine tissue, instructions
Placement
procedure
130. SYSTEMIC LOCAL
250mg/tablet
4 times/day
Total; 10,000mg
Concentration;4-8
micro gram/ml
12.5 mg/fibre
10 days
Total ; 12.5mg
1590 micro gram/ml
COMPARISON OF TETRACYCLINE
131. Disadvantages of fibres
The length of time required for placement (10 minutes or more
per tooth).
The considerable learning curve required to gain proficiency at
placement.
The need for a second patient appointment 10 days after
placement for removal of the fiber.
Also, placement of fibers around 12 or more teeth has resulted in
oral candidiasis in a few cases.
132. DOXYCYCLINE:
Doxycycline is a broad-spectrum semi synthetic tetracycline.
Doxycycline is bacteriostatic, inhibiting bacterial protein
synthesis due to disruption of transfer RNA and messenger RNA
at ribosomal sites.
In vitro testing has shown that Porphyromonas gingivalis,
Prevotella intermedia, Campylobacter rectus, and Fusobacterium
nucleatum, which are associated with periodontal disease, are
susceptible to doxycycline at concentrations of 6.0 mg/ml.
133. Atridox is the only locally applied antimicrobial
agent approved by the FDA & ADA to:
Increase clinical attachment,
Reduce pocket depth
Reduce bleeding on probing in patients with chronic
adult Periodontitis and
135. Upon contact with the crevicular fluid, the liquid
product solidifies and quickly hardens to a wax-like
substance, then allows for controlled release of drug
for a period of 7 days.
136.
137. • Equipment-syringe, cannula
• Preparation of agent- mixing and adaptation of
canula
Description
• Insert canula to base of pocket
• packing
• Hardening of agent
• Periodontal dressing
• Patient instruction
• Appointment for removal
Delivery
140. Mechanical oral hygiene procedures should be avoided on any treated areas for
seven days postoperatively.
Avoid excessive sunlight or artificial ultraviolet light. doxycycline may decrease
the effectiveness of birth control pills.
Atridox must be stored at 2°– 8°C.
Clinical study:
In a 9-month multicenter study Atridox alone was more effective than the other
treatments at all time periods.
For the Atridox group, at 9 months showed a gain of 0.4 mm CAL. reduction in
PD by 0.6 mm and reduction of bleeding on probing was 0.2 units greater than
vehicle control.
The Pharmacokinetic Profile of a Biodegradable Controlled-Release Delivery
System Containing Doxycycline Compared to Systemically Delivered Doxycycline
in Gingival Crevicular Fluid, Saliva, and Serum
Norman H. Stoller, Lonnie R. Johnson, Sheri Trapnell, Charles Q. Harrold, and
Steve Garrett
J Periodontol 1998;69:1085-1091
141. Time (9 months) Gain compared to vehicle
CAL 0.4mm
PROBING DEPTH O.6mm
BOP o.2 units
142. Subgingival Delivery Systemfor Minocycline(Arestin):
A subgingival delivery system of 2% minocycline Hcl
Syringeable gel suspension formulation.
Arestin “microspheres” (minocycline HCL 1mg) indicated as
adjunctive therapy in chronic periodontitis.
Availability - Box with 2 trays, each containing 12 cartridges.
• Each cartridge contains 1 mg of minocycline
• microencapsulated in 3 mg of poly (glycolide-lactide) dry powder.
• Cartridge is inserted into an autoclavable cartridge handle to administer.
143. Minocycline:
• Broad spectrum antibiotic.
• In patients with adult periodontitis, it suppresses spirochetes and
motile rods as effectively as scaling and root planing, suppression
remaining evident for up to 3 months after therapy
• Associated with less photo and renal toxicity than tetracycline,
may cause reversible vertigo
144. Arestin
• Unit dose catridge contains 1mg minocycline
• Sustained release for 14 days
• Refrigeration not needed
• Contraindications –pregnancy, sensitivity
Description
• Insert unit catridge into dispenser handle
• Keep mouth dry
• Insert canula tip deep into pocket
• Activate and adhere on contact with the moisture
Delivery
• probe
• Repeat if necessary
Maintenance
145.
146. 25% more patients in the microsphere group shifted from mean
pd>6mm at baseline to <5mm at 9 month recall
Locally Delivered Minocycline and Guided Tissue Regeneration to Treat
Post-Juvenile Periodontitis. A Case Report
Atsushi Saito, Yasuo Hosaka, Taneaki Nakagawa, Kizuku Seida, Satoru
Yamada, and Katsuji Okuda
This observation suggests that the local delivery of antibiotics and
regenerative therapy may prove to be effective alternative modalities in
treatment of post-juvenile periodontitis. J Periodontol 1994; 65:835-839.
147. Periochip
• Size; 4/5 mm and o.35mm thick
• Shape; rectangular rounded at one end
• Contents;matrix of hydrolized gelatin with 2.5 mg
chx incorporated ;orange brown
• Controlled delivery; biodegradable; maintains high
level -7 to 10 days; 125 ug/ml for
Description
• Site selection
• Chip care and preparation
• Steps in placement
• Action
• Patient instruction
• Maintenance appointments
Placement
procedure
148.
149.
150. Sub-gingival Delivery Of Metronidazole:(Elyzol)
A topical medication contains an oil-based
metronidazole 25% dental gel (glyceryl mono-oleate and sesame oil).
Applied in viscous consistency to the pocket, where it
is liquidized by the body heat and then hardens again
forming crystals in contact with water.
Two 25% gel applications at a 1-week interval have
been used in clinical studies.
Studies of the metronidazole gel have shown it to be
equivalent to SRP but have not shown adjunctive
benefits in conjunction with SRP.
151.
152. Briefly
Biodegradable
Anaerobic bacteria
Bactericidal
>5mm pd
Effects of Topical Metronidazole and Tetracycline in Treatment of
Adult Periodontitis
Tryggve Lie, Georg Bruun, and Olav E. Böe
It was concluded that the augmentative effect of the metronidazole
gel and the tetracycline ointment was comparable but small
compared to scaling and root planing alone
153.
154. Indications of Topical antibiotic
Pocket >5mm(non responding-SRP)
Bleeding on probing
158. Others include …………..
Dental phobic patient
Recent oral cancer
Uncontrolled diabetes
159. Actisite Atridox Arestin Periochip
Ease of use mod ease ease ease
# of sites Multiple
1 – 2
teeth/fibre
8- 15
sites/syringe
1 site/ catridge 1 chips/tooth
Dressing glue yes s/no no no
Gcf
(microg/ml)
15oo 13oo 1000 125
Release days 10 7 (no) 10(no) 10(no)
160. Periostat
Only FDA approved oral,
systemic treatment for
chronic periodontitis that
suppresses activity of tissue
destroying enzyme
Acts as an enzyme
suppressor
Has no antimicrobial activity
No change in bacterial flora
after 18 months
No indication of resistance
For use as an adjunct to
scaling and RP
Promotes cal gain and
Decreased pd in pts
164. In periodontal dressings
In most cases after the surgical periodontal procedures are completed,
the area iv covered by surgical pack.
In general ,dressings have no curative properties; they assist healing by
protecting the tissue rather than providing healing factors
Improved healing and patient comfort with less odor and taste have
been obtained by incorporating antibiotics in the pack.
Bacitracin, oxytetracycycline, neomycin have been tried, but all may
produce hypersensitivity reaction.
Incorporation of tetracycline powder in coe-pack is generally
recommended, particularly when long and traumatic surgeries are
performed.
165. Combination therapy
2630 Combination Therapy with Periostat, Atridox, and Scaling and
Root Planing
M.J. NOVAK1, C.H. DRISKO2, I. MAGNUSSON3, K. KARPINIA, DMD3, M.
BRADSHAW4, C. POWALA5, A.M. POLSON6,
Conclusions: These data demonstrate that the combined use of Periostat and
Atridox with SRP provides significantly and substantially greater clinical
improvements in patients with chronic periodontitis than SRP alone. This study
was supported by Collagenex Pharmaceuticals, Inc.
166. Scaling and root
planing completed
in 2 appointments
in 24 hr period.
Tongue is brushed
with CHX gel for
1 min (1%)
The mouth is
rinsed with 0.2%
CHX sol for 2 min
Pp are irrigated
with a (1%)CHX
sol
Full mouth disinfection-Quiryen et al
167. CONCLUDING COMMENTS
As a monotherapy, local drug delivery systems incorporating a variety of drugs
can improve periodontal health.
There is no single universal drug that would be effective in all situations
. Local drug delivery often appears to be as effective as scaling and root planing
with regards to reducing signs of periodontal inflammatory disease
Local drug delivery systems usually do not provide a benefit beyond what is
achievable with conventional scaling and root planing in the treatment of adult
periodontitis. Therefore, their routine utilization is unnecessary.
168. Local delivery may be an adjunct to conventional therapy. The sites most likely
to be responsive to this adjunctive treatment method may have refractory or
recurrent periodontitis, or specific locations where it is difficult to instrument
root surfaces. However, the data are limited to support this concept.
At present, there are insufficient data to indicate that one local drug delivery
device is clearly superior to all the other systems. However, desired
characteristics include ease of placement, controlled release of drugs and
resorbability.
In conjunction with conventional treatment, systemically administered drugs
appear to be as effective as local drug delivery.
To date, results from studies assessing local drug delivery systems have not
justified extending the time interval between supportive periodontal
maintenance visits.
169. There are preliminary, but very limited data, regarding the ability of local
delivery to help suppress future disease progression.
There are insufficient data to indicate that local drug delivery induces
bacterial resistance to antimicrobial agents. Long-term studies are needed to
address this important issue.
Additional studies are needed to evaluate if local delivery is effective against
tissue invasive organisms.
There is a lack of data to support the impression that local drug delivery in
conjunction with root planing reduces the need for periodontal surgery more
than scaling and root planing alone.
. However, additional randomized, controlled studies are needed to help
delineate the types of lesions, periodontal diseases, or specific situations where
local delivery systems would be most beneficial.
170.
171. Antibiotics Interacting drug Effect Clinical
significance
Metronidazole
Barbiturates&
hydantoins
↓ effectiveness of
Metronidazole
Probable
Oral anticoagulants
(warfarin)
↑ anticoagulant effect
Definite
Ethanol Disulfiram-like reaction
Probable
Clindamycin Anti-diarrheals
(kaolin)
↓ absorption of
Clindamycin
Probable
Muscle
relaxants(diazepam)
↑ frequency & duration
of respiratory paralyses
Probable
Erythromycins Mutual antagonism
Probable
Penicillins
(amoxicillin)
Probenecid ↑ level of
Penicillins
Probable
Important Antibiotic Drug Interactions
172. Beta lactams antibiotics (penicillins and cephalosporins) mechanismof action videos and
Fluroquinolone
(ciprofloxacin)
Cations (Al+++, Ca++,
Fe++, Mg++, Zn++) in
antacids, vitamins
↓ absorption of
Fluroquinolones due to
chelation Definite
Caffeine ↑ Caffeine
concentration
Probable
NSAIDs ↑ risk of stimulation of
CNS
Definite
Probenecid ↓ ciprofloxacin
clearance
Probable
Theophylline ↑ serum levels of
Theophylline
Definite
Oral
anticoagulants
warfarin)
↑ anticoagulant
effect
Probable
173. Tetracyclines
(doxycycline)
Antacids, aluminum, bi, Fe.
Mg++
↓ absorption of
Tetracyclines
Probable
Barbiturates&
hydantoins
↓ serum half of
doxycycline
Probable
Carbamazepine ↓ serum half of
doxycycline
Probable
Digoxin ↑ serum levels of Digoxin
Probable
174. Erythromycins
(Azithromycin
Clarithromycin)
Carbamazepine
↑ serum levels of
Carbamazepine with
nausea, vomiting Definite
Cisapride
↑ Cisapride
concentration with life-
threatening
arrhythmias
Definite
Cyclosporine
↑ serum levels of
Cyclosporine with
toxicity Probable
Methylprednisolone
↑ steroid concentration
Definite
Theophylline
↑ serum levels of
Theophylline with
nausea, vomiting Definite
Oral anticoagulants
(warfarin)
↑ anticoagulant effect
Probable
175. Comparison
When comparing the efficacy of local and systemic drug delivery, several
issues need to be considered.
For instance, systemic medications ensure drug delivery to the base of the
pocket, treat potential reservoirs of bacterial reinfection, affect tissue
invasive organisms, take less time, treat multiple sites simultaneously, are
less expensive and a variety of drugs are available
. In contrast, local delivery provides high drug concentration, minimal side
effects, less reliance on patient compliance for taking the medication, and
avoids treating the patient systemically. Each drug delivery system has its
merits.
However, for the patient with multiple diseased sites, utilization of
systemic drugs may be more practical.
On the other hand, it could be contended that local delivery systems which
provide high site concentrations of drugs may have less potential of
inducing resistant bacterial strains in other parts of the body (e.g., the
colon) than systemic administration of antibiotics which achieve low drug
levels.10
Since this issue is unresolved, and considering the global problem of
emerging resistance to antimicrobials, antibiotics should only be used
when there is a clear indication for their need.
177. Prudent administration of antimicrobial agents following judicious
pharmacologic principles will preclude the abuse of
chemotherapeutic agents and reduce the potential of developing
or selecting drug resistant bacterial strains.
Local drug delivery systems with controlled release properties
have the potential to be used as a therapeutic component in the
management of periodontal diseases.
However, additional randomized, controlled studies are needed
to help delineate the types of lesions, periodontal diseases, or
specific situations where local delivery systems would be most
beneficial.
