AMAS in DENTISTRY.pptx.pptx antimicrobial agents in dentistry

ANTIBIOTICS
PRESENTED BY:
DR.DR.AARTI TALWAR

CONTENTS
● INTRODUCTION
● HISTORY
● PIONEERS OF
ANTIMICROBIAL THERAPY
● TERMINOLOGIES
● IDEAL CHARACTERISTICS
● CLASSIFICATION
● SELECTION OF
ANTIBIOTICS
● ADVERSE EFFECTS
● RESISTANCE TO
ANTIBIOTICS
● COMBINATION THERAPY
● CHEMOPROPHYLAXIS
● ANTIBIOTIC PROPHYLATIC
REGIMEN FOR DENTAL
PROCEDURES
● ANTIBIOTICS IN
DENTISTRY
● SYSTEMIC ANTIBIOTICS
● LOCAL DRUG DELIVERY
AGENTS
● CONCLUSION
● REFERENCES

3
INTRODUCTION
● Antibiotics are a naturally occurring, semisynthetic or synthetic
type of antimicrobial agent that destroys or inhibits the growth
of selective microorganisms, generally at low concentrations.
-can kill or stop the multiplication of bacterial cells,
-at concentrations that are relatively harmless to host tissues,
-and therefore can be used to treat infections caused by
bacteria.

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ANTIBIOTIC ("opposing life“)
Greek roots
anti bios
"against" "life”
refer to any substance used against microbes.
● The term 'antibiosis', meaning "against life", was introduced by
the French bacteriologist Jean Paul Vuillemin as a descriptive
name of the phenomenon exhibited by antibacterial drugs.
● The word "chemotherapy" was coined by Ehrlich. Ehrlich has
been called the father of chemotherapy and the development
of synthetic antimicrobial agents.

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HISTORY The history of antimicrobial
chemotherapy goes back in time
long before the understanding
and the recognition of the agents
that are responsible for such
infection.
Mercury, for example, has been
used in the treatment of syphilis
since the 16th century .
The use of quinine as an
antimalarial agent can also be
traced back as long ago as the
17th century.

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1846 SEMMELWEISS
Demonstrated use of antiseptics in the
control of infection using chlorine .
Importance of hand washing.
1865 JOSEPH LISTER
Father of modern surgery.
Father of antiseptic surgery.
1884 HANS CHRISTIAN GRAM
Gram stain.
1889 VUILLEMIN
"antibiosis" was introduced
PIONEERS IN ANTIMICROBIAL CHEMOTHERAPY

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• 1907 PAUL EHRLICH
• discovered p-rosaniline to treat syphilis.
Ehrlich postulated that it would be possible to
find chemicals that were selectively toxic for
parasites but not toxic to humans. This idea
has been called the “magic bullet” concept.
.
1930 GERHARD DOMAGK
discovered the protective effects of
prontosil, the forerunner of sulfonamide.

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1929 ALEXANDER FLEMING
published his observation on antibiotic activity in a
species of Penicillium. However, this was not
appreciated at the time of Fleming's observation and
was only established ten years later by the work of
Florey and Chain and their colleagues at Oxford.
1944 Waksman
renamed the term from 'antibiosis' to
'antibiotics'.
Father of Antibiotics
By the 1960s, improvements in fermentation techniques and advances in
medicinal chemistry permitted the synthesis of many new
chemotherapeutic agents

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● DRUG: any substance or product that is used or is intended to be
used to modify or explore physiological systems or pathological states
for the benefit of the recipient. WHO (1966)
● ANTIBIOTICS- Substance produced by microorganisms that have the
capacity to kill or inhibit the growth of other microorganisms at very
low concentration.
● ANTIMICROBIAL THERAPY- Synthetic as well as naturally obtained
drugs that act against microorganisms either systemically or at
specific sites.

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● ANTISEPTIC- antimicrobial substance or compound that is applied to living
tissue/skin to reduce the possibility of infection, sepsis, or putrefaction.
Antiseptics are generally distinguished from antibiotics by the latter's ability to
safely destroy bacteria within the body, and from disinfectants, which destroy
microorganisms found on non-living objects.
● CHEMOTHERAPY-treatment of infectious diseases or malignancy with drugs to
destroy microorganisms or cancer cells preferentially with minimal damage to
host tissues.The infection maybe due to bacteria,fungi ,virus etc.
● MINIMUM INHIBITORY CONCENTRATION- minimum concentration of an
antibiotic that prevents visible growth of a microorganism.

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1. Selectively toxic to the microbe but nontoxic to host cell.
2. Microbicidal rather than microbiostatic.
3. Relatively soluble , function even when highly diluted in body fluid.
4. Remain potent long enough to act and is not broken down or excreted
prematurily.
5. Do not lead to the development of antimicrobial resistance.
6. Do not disrupt the host health by causing allergies or predisposing the host to
other infection.
7. Reasonably priced.
IDEAL CHARACTERISITICS

CLASSIFICATION
MECHANISM OF ACTION
TYPE OF ACTION SOURCE
SPECTRUM OF ACTIVITY
TYPE OF
ORGANISM

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MECHANISM OF ACTION
● INHIBIT CELL WALL SYNTHESIS=penicillins,cephalosporins,vancomycin
● AFFECT CELL MEMBRANE FUNCTION= amphotericin B,nystatin
● INHIBIT PROTEIN SYNTHESIS=
chloramphenicol,tetracyclines,erythromycin
● ALTER PROTEIN SYNTHESIS= aminoglycosides
● INHIBIT DNA SYNTHESIS= acyclovir,zidovudine
● AFFECT DNA FUNCTION= rifampicin,metronidazole
● INHIBIT DNA GYRASE= fluoroquinolones
● ANTIMETABOLITES= sulphonamides,dapsone.

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TYPE OF ACTION
BACTERICIDAL AGENTS:
penicillins,cephalosporins,aminoglycosides,fluoroquinolones,rifampicin,
metronidazole
BACTERIOSTATIC AGENTS:
tetracyclines,chloramphenicol,sulphonamides,dapsone,erythromycin,
clindamycin
SPECTRUM OF ACTIVITY
NARROW SPECTRUM
Penicillin G
Aminoglycosides
BROAD SPECTRUM
Tetracycline
Chloramphenicol

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SOURCE OF ANTIBIOTICS
• Fungi-
Penicillin,
Griseofulvin,
Cephalosporin
• Bacteria-Polymyxin B,
Bacitracin
• Actinomycetes-Aminoglycosides,
Macrolides,Tetracyclines

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TYPE OF ORGANISM AGAINST WHICH IT IS
ACTIVE
● Antibacterial - Penicillin , Aminoglycosides, Erythromycin
● Antifungal - Amphotericin B, Ketoconazole,
● Antiviral - Zidovudine , Acyclovir
● Antiprotozoal - Chloroquine , Metronidazole
● Antihelminthic - Mebendazole , Pyrantel

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SELECTION OF AN APPROPRIATE ANTIMICROBIAL AGENT
Patient factors
Age • History of
allergy • Genetic
abnormalities •
Pregnancy • Host
defences • Hepatic
dysfunction • Renal
dysfunction • Local
factors
Drug factors
• Route of
administration •
Spectrum of
antimicrobial
activity
•Bactericidal/Bac
teriostatic effect
• Ability to cross
blood–brain
barrier • Cost of
the AMA
Organism-related
factors
Clinical
diagnosis:
empirical therapy
• Bacteriological
reports •
Resistance to
AMAs • Cross-
resistance

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PATIENT FACTORS
1. Age: May affect kinetics of many Antimicrobial agents.
Use of chloramphenicol in premature infants may produce gray-baby syndrome
because the metabolic functions of the liver and renal excretion are not fully
developed. Renal function declines with age; hence, elderly patients are more
prone to ototoxicity and nephrotoxicity with aminoglycosides due to its reduced
clearance by the kidney.
2. History of allergy: In patients with history of asthma, allergic rhinitis, hay fever,
etc. there is an increased risk of penicillin allergy; hence such drugs should be
avoided.

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3.Genetic abnormalities: Primaquine, pyrimethamine, sulphonamides,
sulfones, fluoroquinolones, etc. may cause haemolysis in patients with
glucose-6-phosphate dehydrogenase (G6PD) deficiency.
4. Pregnancy: Most of the AMAs cross the placental barrier and may affect
the developing foetus. The risk of teratogenicity is highest during the first
trimester. For example, use of tetracyclines during pregnancy may affect
foetal dentition and bone growth. There is an increased incidence of
hepatotoxicity with tetracycline in pregnant women. Penicillin,
erythromycin, cephalosporins are considered safer.

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5.Host defences: In immunocompromised patients (AIDS, leukaemias and other
malignancies), normal defence mechanisms are impaired—bacteriostatic drugs may
not be adequate; hence bactericidal agents should be used to treat infection.
6.Hepatic dysfunction: In patients with hepatic dysfunction, drugs like
chloramphenicol, erythromycin, rifampin, etc. should be avoided or require dose
reduction to avoid toxic effects.
7.Renal dysfunction: In renal failure, drugs that are eliminated via kidney can
accumulate in the body and cause severe toxic effects. Hence aminoglycosides,
vancomycin, amphotericin B, fluoroquinolones etc. should be avoided or require
dose reduction in patients with impaired renal function.

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8. Local factors:
● Antimicrobial activity of sulphonamides is markedly reduced in the presence
of pus.
● The activity of aminoglycosides is enhanced at alkaline pH,
● Presence of necrotic material and foreign body makes eradication of infection
practically impossible.
● Hematomas foster bacterial growth. eg: Tetracycline, Penicillin and
cephalosporin get bound to degraded Hb in the hematomas.
● Penetration barrier may hamper the access of the Antimicrobial agents to the
site of infection in sub acute bacterial endocarditis.

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DRUG FACTORS
● 1. Route of administration: Depending upon the severity and site of infection,
the AMAs have to be chosen. Some of the AMAs can be administered orally as
well as parenterally. For mild-to-moderate infections, oral route is usually
preferred, but for severe infections like endocarditis, meningitis, etc. parenteral
antibiotics are preferred during initial stages of therapy.
● 2.The spectrum of antimicrobial activity: For definite therapy, narrow
spectrum drugs is preferred.For empirical therapy, broad spectrum drug is
preferred.
● 3. Bactericidal/bacteriostatic effect: Bactericidal drugs kill the organisms while
static drugs inhibit growth and multiplication. In immunocompromised states,
the host-defence mechanisms are impaired; hence bactericidal drugs are
required.

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● 4. Ability to cross blood–brain barrier (BBB): Pharmacokinetic profile of
the drug is important, e.g. clindamycin is effective against anaerobes, but
not useful for anaerobic brain abscess as it does not reach cerebrospinal
fluid (CSF) and brain. Anaerobic brain abscess can be treated effectively
with third-generation cephalosporins or combination of metronidazole
and chloramphenicol.
● 5. Cost of the antimicrobial agent: The cost of treatment has to be
considered while selecting an antimicrobial agent. The expensive
antimicrobials should not be used routinely when alternative cheaper and
effective AMAs are available.

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ORGANISM RELATED CONSIDERATIONS
● Clinical diagnosis itself directs choice of the Antimicrobial agents.
● A good guess can be made, from the clinical features and the local
experience about the type of organism and its sensitivity.
● Choice to be based on bacteriological examination, if no guess can be
made about the infecting organism and its sensitivity, AMA should be
selected on the basis of Culture and sensitivity testing.

ADVERSE EFFECTS OF ANTIMICROBIALAGENTS
Toxicity
Hypersensitivit
y
Drug
resistance
Superinfection
Nutritional
deficiencies
Masking of an
infection
26

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TOXICITY
• Local Irritancy:
 Experienced at the site of administration.
 Local irritation, pain and abscess formation at
the site of i.m injection, thrombophlebitis of
the injected vein are the complications. eg:
Erythromycin, Tetracyclines,
• Systemic Toxicity:
 All AMAs produce dose related and
predictable organ toxicities. eg :
Aminoglycosides, Amphotericin B,
Tetracycline

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HYPERSENSITIVITY REACTIONS
• All AMAs are capable of causing hypersensitivity reactions which are
unpredictable and unrelated to dose.
• They may range from rashes to anaphylactic shock
○ eg: Penicillin, Cephalosporin, Sulfonamides

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DRUG RESISTANCE
Natural Resistance :
Some microbes have always been resistant to certain
AMAs. They lack the metabolic process or the target
site which is affected by the particular drug.
Acquired Resistance :
It is the development of resistance by an organism (which was
sensitive before) due to the use of an AMA over a period of
time. This is considered to be a major clinical problem.
It refers to unresponsiveness of a microorganism to an
AMA. Resistance maybe acquired through
mutation or gene transfer.

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GENE TRANSFER (Infectious Resistance) :
• The resistance causing gene is passed from one organism to the
other.
• Rapid spread of resistance can occur by this mechanism.
• The transfer of genes for drug resistance occurs by the following
mechanisms:
• Transduction
• Transformation
• Conjugation

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Conjugation
● : Conjugation is the transfer of genetic material carrying resistance between bacteria by
direct contact through sex pilus, e.g. Escherichia coli resistance to streptomycin.

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Transduction
● There is transfer of DNA carrying a gene for resistance from one bacterium to another
through bacteriophage, e.g. resistance of strains of Staphylococcus aureus to antibiotics is
mediated via transduction.

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Transformation
The resistance carrying genetic material that is released into the environment by resistant
bacteria is taken up by other sensitive bacteria, e.g. penicillin G resistance in pneumococci.

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MUTATION :
● It is a stable and heritable genetic change that occurs spontaneously and randomly among
microorganisms.
● Antibiotic resistance occurs when an infection responds poorly to an antibiotic that once could
treat it successfully. It’s the bacteria that have become resistant to the antibiotic, not the
patient
● a change in their DNA - that gives them a new protein as a tool to fight the antibiotic.

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There are many mechanisms by which this tool may work
prevent the antibiotic
from entering the
bacterial cell;
pump the antibiotic
out of the cell;
destroy the antibiotic by
enzymatic reaction;
modify the
antibiotic’s target so
it no longer binds to
the drug;

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Cross-resistance
● Organisms that develop resistance to an antimicrobial agent may also show
resistance to other chemically related AMAs.
● The cross-resistance among AMAs could either be one-way or two-way. Cross-
resistance among tetracyclines and sulphonamides is usually ‘two-way’.
● The ‘one-way’ resistance is seen between neomycin and streptomycin.
Neomycin-resistant organisms are resistant to streptomycin but streptomycin-
resistant organisms may be sensitive to neomycin.

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Prevention of development of resistance to antimicrobial agents
It is done by:
1. Selecting right antimicrobial agent.
2. Giving right dose of the AMA for proper duration.
3. Proper combination of AMAs, e.g. in tuberculosis (TB), multidrug therapy
(MDT) is used to prevent development of resistance to antitubercular drugs by
mycobacteria.
4.Rapidly acting and narrow spectrum AMAs should be preferred whenever
possible.
5.Combinations of AMAs should be used whenever prolonged therapy is
undertaken.
6.Infection by organisms notorious for developing resistance must be treated
intensively.

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Superinfection (Suprainfection)
● It is defined as the appearance of a new infection due to antimicrobial
therapy. The causative organism of superinfection should be different
from that of the primary disease.
Use of most AMAs causes some alterations in the normal microbial flora
of the body.
The normal flora contributes to host defence by elaborating substances,
which inhibit pathogenic organisms.

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● Also the pathogen has to compete with the normal flora for
nutrients to establish itself. Lack of competition may allow even
a normally nonpathogenic component of the flora to
predominate and invade.
● Suprainfection are more common when host defence is
compromised, as in:
• Corticosteroid therapy
• Leukemias and other malignancies
• AIDS
• Agranulocytosis
• Diabetes

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● It can be minimized by
● (i) using specific antimicrobial agents,
● (ii) avoiding unnecessary use of AMAs and
● (iii) use of probiotics, e.g. Lactobacillus.

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NUTRITIONAL DEFICIENCIES
● Prolonged use of AMAs alters the intestinal flora which synthesize some of
the B complexes and Vitamin K – results in vitamin deficiencies.
MASKING OF AN INFECTION
• A short course of an AMA may be sufficient to treat one infection but
only briefly suppress another one contacted concurrently.
• The other infection will be masked initially, only to manifest later in a
severe form.
• Eg: Syphilis masked by the use of single dose of penicillin which is
sufficient to cure gonorrhoea

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COMBINATION OF ANTIMICROBIAL AGENTS
● It is the simultaneous use of two or more antimicrobial agents for the
treatment of certain infectious diseases.
Indications/advantages of antimicrobial combinations
● 1. To broaden the spectrum of activity in mixed bacterial infections:
Odontogenic infections, brain abscess, etc. are often due to both aerobic
and anaerobic organisms. Hence, they require antimicrobial combination
therapy. Metronidazole + ampicillin for ulcerative gingivitis.
● 2. In severe infections when the aetiology is not known: Combination of
antimicrobial agents is used for empirical therapy. Later, the AMA should
be selected according to the type of organism, culture and sensitivity
results.

43
● 3. To increase antibacterial activity in the treatment of specific infections (for
synergistic effect).
■ Synergism may manifest in terms of decrease in MIC of one AMA in
presence of another, or the MICs of both may be lowered.
■ If MIC of both are lowered by 25 % or less, the pair is considered
synergistic.
■ 25-50% of each is considered additive.
■ More than 50% indicate antagonism.
■ A synergistic drug sensitizes the organisms to the action of the other
member of the pair.
■ This may manifest as a more rapid lethal action of the combination than
either of the individual members.
● Ampicillin + gentamicin for enterococcal endocarditis.
● Carbenicillin + gentamicin for infections due to Pseudomonas.
Penicillins, by inhibiting bacterial cell wall synthesis, facilitate the entry of gentamicin
into the bacterial cell (synergistic effect).

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● 4. To prevent emergence of resistant microorganisms: In tuberculosis (TB),
leprosy and HIV infection, combination therapy is used.
● 5. To reduce duration of therapy: Multidrug therapy is used in TB and leprosy.
● 6. To reduce adverse effects: Amphotericin B (AMB) and flucytosine in
cryptococcal meningitis: the dose-dependent toxicity (especially
nephrotoxicity) of AMB is reduced due to reduction in the dosage

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DISADVANTAGES OF ANTIMICROBIAL DRUG COMBINATIONS
1. Increased toxicity, e.g. vancomycin with tobramycin may cause enhanced
nephrotoxicity.
2. Increased cost.
3. Decreased antibacterial activity due to improper combinations, e.g. in
pneumococcal meningitis, activity of penicillin G (bactericidal) against pneumococci
will decrease if combined with tetracycline (bacteriostatic).
4. Increased likelihood of superinfection.
5. Irrational combination of AMAs can lead to development of resistance.

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CHEMOPROPHYLAXIS
● Chemoprophylaxis is the administration of antimicrobial agents to prevent
infection or to prevent development of disease in persons who are already
infected . The ideal time to initiate therapy is before the organism enters the
body or at least before the development of signs and symptoms of the disease.
The difference between treating and preventing infection is that treatment is directed
against a specific organism infecting an individual patient, while prophylaxis is often
against all organism capable of causing infection.

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prevent endocarditis in patients with
valvular lesion before undergoing any
surgical procedures: Surgical
procedures mucosal damage
bacteraemia affects damaged valve
endocarditis.
protect healthy persons: Chloroquine
/mefloquine is used for chemoprophylaxis
of malaria for those travelling to malaria-
endemic area.
prevent infection in patients undergoing organ
transplantation: Oral fluoroquinolones can be used.
INDICATIONS

48
prevent opportunistic infections in
immunocompromised patients, e.g.
cotrimoxazole is used to prevent
Pneumocystis jiroveci pneumonia in AIDS
patients.
Prior to surgical procedures: in patients who
are diabetics or on prolonged corticosteroids
to prevent wound infection after surgery.
prevent infection in patients with burns: Topical silver
sulphadiazine and systemic antibiotics are used.

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SUGGESTED CHEMOPROPHYLACTIC REGIMENS
● The effectiveness of chemoprophylaxis depends on the selection of specific
antimicrobial agent, its dosage, time of initiation and duration of antimicrobial
therapy.
● Empirical therapy: It is the use of antimicrobial agents before the identification
of causative organism or availability of susceptibility test results, e.g.
combination of amoxicillin, cefotaxime and vancomycin is used as empirical
therapy for suspected bacterial meningitis (before test results are available) to
cover possible organisms likely to cause meningitis.
● Definitive therapy: It involves the use of antimicrobial agent after identifi
cation/susceptibility tests of causative organism responsible for the disease.

50
ANTIBIOTIC PROPHYLACTIC REGIMEN FOR DENTAL PROCEDURES

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SYSTEMIC ADMINISTRATION OF ANTIBIOTICS IN PERIODONTAL THERAPY
■ Systemic antibiotics are considered to enter the periodontal tissue and
the periodontal pocket through transudation from the blood stream.
■ The antibiotics within the periodontal connective tissue then cross the
crevicular and junctional epithelia into the crevicular region around the
tooth, into the GCF, associated with the subgingival plaque

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● They are administered :
■ Patients who do not respond to conventional mechanical
therapy.
■ Acute periodontal infections associated with systemic
manifestations.
■ Prophylaxis in medically compromised patients.
■ Adjunct to surgical and non surgical periodontal therapy.

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■ The antimicrobial concentration in the GCF will be inadequate
without the mechanical disruption of the microbial biofilm
adherent to the tooth, i.e, subgingival plaque and calculus.
■ The systemic antibiotic therapy may also suppress the
periodontal pathogens in other parts of the mouth including
tongue and the mucosal surfaces.
■ This additional effect is considered beneficial because it may
delay subgingival recolonization of pathogens.

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DISADVANTAGES
■ Inability to achieve high GCF concentrations
■ Adverse drug reactions
■ Resistant microorganisms
■ Uncertain patient compliance

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ANTIBIOTICS IN PERIODONTICS
The principle antibiotic groups have been extensively evaluated for treatment of
the periodontal diseases
1. Tetracycline
2. Minocycline
3. Doxycycline
4. Erythromycin
5. Clindamycin
6. Ampicillin
7. Amoxicillin
8. Metronidazole

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TETRACYCLINE
● Group of broad-spectrum antibiotic compounds
● The first members of the tetracycline group to be described
were chlortetracycline and oxytetracycline.
● Chlortetracycline was first discovered as an ordinary item in
1945 by Benjamin Minge Duggar. Duggar derived the
substance from a Missouri soil sample, golden-colored, fungus-
like, soil-dwelling bacterium named Streptomyces aureofaciens.
● Oxytetracycline (terramycin) was isolated in 1949 by Alexander
Finlay from a soil sample collected on the grounds of a factory
in Terre Haute, Indiana.
● The Pfizer group, led by Francis A. Hochstein, determined the
structure of oxytetracycline, enabling Lloyd H. Conover to
successfully produce tetracycline itself as a synthetic product in
1955.

57
● Tetracycline molecules comprise a linear fused tetracyclic nucleus (rings
designated A, B, C and D) to which a variety of functional groups are
attached. Tetracyclines are named for their four ("tetra-") hydrocarbon rings ("-
cycl-") derivation ("-ine").
● While all tetracyclines have a common structure, they differ from each other by
the presence of chloride, methyl, and hydroxyl groups. These modifications do
not change their broad antibacterial activity, but do affect pharmacological
properties such as half-life and binding to proteins in serum.

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● Removal of the dimethylamine group at C4 reduces antibacterial
activity.Replacement of the carboxylamine group at C2 results in reduced
antibacterial activity but it is possible to add substituents to the amide nitrogen
to get more soluble analogs like the prodrug lymecycline. The simplest
tetracycline with measurable antibacterial activity is 6-deoxy-6-
demethyltetracycline.
● growth inhibitors (bacteriostatic) rather than killers of the infectious agent (
bacteriocidal) and are only effective against multiplying microorganisms.
● Concentration in the gingival crevice is 2-10 times than in serum

60
Pharmacokinetics
● When ingested, it is usually recommended that the more water-soluble, short-
acting tetracyclines (plain tetracycline, chlortetracycline, oxytetracycline,
demeclocycline and methacycline) be taken with a full glass of water, either two
hours after eating or two hours before eating. This is partly because most
tetracyclines have chelating property and bind with food and also easily with
magnesium, aluminium, iron and calcium, which reduces their ability to be
completely absorbed by the body.

61
● Dairy products, antacids and preparations containing iron should be avoided
near the time of taking the drug. Partial exceptions to these rules occur for
doxycycline and minocycline, which may be taken with food (though not iron,
antacids, or calcium supplements). Minocycline can be taken with dairy
products because it does not chelate calcium as readily, although dairy
products do decrease absorption of minocycline slightly.
● Tetracyclines are widely distributed throughout the body, get concentrated in
liver, spleen, bone, dentine, enamel of unerupted teeth but concentration in
CSF is relatively low. They cross placental barrier, are metabolized in liver and
excreted in urine. Doxycycline is excreted mainly in the faeces via bile.
Therefore, doxycycline is safe for use in patients with renal insufficiency.
Doxycycline undergoes enterohepatic cycling.

62
Mechanism of action
● Tetracycline antibiotics are protein synthesis inhibitors.They inhibit translation
process by binding to 30S subunit of bacterial ribosome and Prevent binding of
aminoacyl tRNA to A site of ribosome.

63
unwinding
transcription
codons

64
A (aminoacyl) site, which accepts
the incoming aminoacylated tRNA
P (peptidyl) site, which holds
the tRNA with the nascent
peptide chain
E (exit) site, which holds the
deacylated tRNA before it
leaves the ribosome.
translation

65
Tetracycline binds to 30s
subunit

66
RESISTANCE :
3 mechanisms of resistance to tetracycline have been described :
■ Decreased intracellular accumulation due to either impaired
influx or increased efflux by an active transport protein pump.
■ Ribosome protection due to production of proteins that
interfere with tetracycline binding to the ribosome.
■ Enzymatic inactivation of tetracyclines.

67
Adverse effects
1. Gastrointestinal: On oral administration, they can cause GI irritation manifested
as nausea, vomiting, epigastric distress, abdominal discomfort and diarrhoea.
2. Phototoxicity: It is particularly seen with demeclocycline and doxycycline. They
may also produce sunburn-like reaction in the skin on exposure to sunlight. They
may also produce pigmentation of the nails.

68
3. Effects on bones and teeth: Tetracyclines have calcium-chelating property, form
tetracycline–calcium orthophosphate complex, which is deposited in growing bone
and teeth. Use of tetracyclines in children and during pregnancy can cause
permanent brownish discolouration of the deciduous teeth due to deposition of the
chelate in the teeth. There is increased incidence of caries in such teeth.
Tetracyclines also affect the linear growth of bones. The incidence of hepatotoxicity
is more in pregnant women. Therefore, tetracyclines are contraindicated during
pregnancy in the interest of both foetus and mother. It is also contraindicated in
children up to the age of 8 years.

69
4. Superinfection: It is common with older tetracyclines because of their incomplete absorption in
the gut; they cause alteration of the gut flora. Superinfection occurs with organisms resistant to
tetracyclines like Candida, Proteus, Pseudomonas, C. difficile, etc.
5. Hepatotoxicity: Acute hepatic necrosis with fatty changes is common in patients receiving high
doses ( 2 g/day) intravenously. It is more likely to occur in pregnant women.
6. Renal toxicity: Demeclocycline may produce nephrogenic diabetes insipidus by inhibiting the
action of antidiuretic hormone (ADH) on collecting duct. Fanconi syndrome: Use of outdated
tetracyclines may damage the proximal renal tubules—the patient may present with nausea,
vomiting, polyuria, proteinuria, acidosis, etc.
7. Hypersensitivity reactions: Skin rashes, fever, urticaria, exfoliative dermatitis, etc. may occur
rarely. Cross-sensitivity among tetracyclines is common.

PRODUCT(S) CONTAINING
TETRACYCLINE
70

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TETRACYCLINE SYSTEMIC
Achromycin 250 MG Capsule-Manufactured By Pfizer Ltd.
● treatment of bacterial infections acne, bacterial infection, bladder infection,
bronchitis, brucellosis etc..
● Substitutes:Alcyclin 250 MG Capsule, Hostacycline 250 MG Capsule
Rancycline 250 MG Capsule, Tetracycllin 250 MG Capsule
Brand names: Sumycin, Tetracap, Tetracon

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TETRACYCLINE TOPICAL
● Brand names: Topicycline
Tetracycline topical is used in the treatment of: Acne, Bacterial Skin Infection
MULTI-INGREDIENT MEDICATIONS CONTAINING
TETRACYCLINE:
● bismuth subcitrate potassium/metronidazole/tetracycline systemic
● Brand names: Pylera
Drug class(es): H. pylori eradication agents
● diphenhydramine/hydrocortisone/nystatin/tetracycline topical
● Brand names: FIRST Mary's Mouthwash
Drug class(es): mouth and throat products

73
USES IN DENTISTRY
● Used in the treatment of refractory periodontitis including
Localised Aggressive Periodontitis.
• Ability to concentrate in the GCF and inhibit the growth of A.
actinomycetemcomitans.
• They exert an anticollagenase effect that can inhibit tissue
destruction.
• The combination therapy allows mechanical removal of root
surface deposits and elimination of pathogenic bacteria from
within the tissues.

74
■ Effective in treating periodontal diseases in part because their
concentration in the gingival crevice is 2 to 10 times that in serum.
■ This allows a high drug concentration to be delivered into periodontal
pockets.
■ In addition, several studies have demonstrated that tetracyclines at a
low gingival crevicular fluid concentration (2 to 4 g/ml) are very
effective against many periodontal pathogens.

75
DOXYCYCLINE
● Charlie Stephens' group at Pfizer created doxycycline--greatly improved stability
and pharmacological efficacy. It was clinically developed in the early 1960s and
approved by the FDA in 1967.
● Doxycycline, like other tetracycline antibiotics, is bacteriostatic. It works by
preventing bacteria from reproducing through the inhibition of protein
synthesis.
HIGHLY LIPOPHILIC
SO CAN EASILY ENTER CELLS
DRUG IS EASILY ABSORBED
AFTER ORAL
ADMINISTRATION
LARGE VOLUME OF
DISTRIBUTION
RE-ABSORBED IN
THE RENAL
TUBULES AND GIT
LONG
ELIMINATION
HALF LIFE
DOES NOT ACCUMULATE IN THE KIDNEYS
OF PATIENTS WITH KIDNEY FAILURE DUE
TO THE COMPENSATORY EXCRETION IN
FAECES

76
Advantages of doxycycline
1. It can be administered orally as well as intravenously.
2. It is highly potent.
3. It is completely absorbed after oral administration.
4. Food does not interfere with its absorption.
5. It has a longer duration of action (t/2–24 h).
6. Incidence of diarrhoea is rare as it does not affect the intestinal flora.
7. It can be safely given to patients with renal failure, as it is excreted primarily in
bile.
8.Doxycycline–metal ion complexes are unstable at acid pH, therefore more
doxycycline enters the duodenum for absorption than the earlier tetracycline
compounds.

PRODUCT(S) CONTAINING
DOXYCYCLINE
77

DOXYCYCLINE SYSTEMIC
Monodox (Oral)
● Generic name: doxycycline (oral route)
● Brand names: Vibramycin, Monodox, Vibra-Tabs, Oracea, Acticlate
CAP®
,Doryx®
used in the treatment of: Acne, Actinomycosis, Amebiasis ,Anthrax,
Bacterial Infection.
● Dosage Forms:Powder for Suspension, Capsule,Tablet, Syrup

79
● For oral dosage forms (capsules, suspension, syrup, tablets):For infections:
○ Adults—100 milligrams (mg) every 12 hours on the first day, then 100 mg
once a day or 50 to 100 mg every 12 hours.
○ Children 8 years of age or older weighing 45 kilograms (kg) or more—100
mg every 12 hours on the first day, then 100 mg once a day or 50 to 100
mg every 12 hours.
○ Children 8 years of age or older weighing less than 45 kg—Dose is based
on body weight and must be determined by your doctor. The dose is
usually 4.4 mg per kg of body weight per day and divided into 2 doses on
the first day of treatment. This is followed by 2.2 mg per kg of body
weight per day, taken as a single dose or divided into two doses on the
following days.

80
● PERIOSTAT
Generic Name: doxycycline hyclate
Brand Name: Periostat
Drug Class: Tetracyclines
available as a 20 mg tablet formulation of doxycycline for oral administration.
● Doxycycline hyclate is a yellow to light-yellow crystalline powder which is
soluble in water.
● Inert ingredients in the formulation are: hydroxypropyl methylcellulose, lactose,
magnesium stearate, microcrystalline cellulose, titanium dioxide, and triacetin.
Each tablet contains 23 mg of doxycycline hyclate equivalent to 20 mg of
doxycycline.

81
INDICATIONS
● Periostat® (doxycycline hyclate) is indicated for use as an adjunct to scaling and
root planing to promote attachment level gain and to reduce pocket depth in
patients with adult periodontitis.
DOSAGE
Periostat® 20 mg twice daily as an adjunct following scaling and root planing may be
administered for up to 9 months.
should be taken twice daily at 12 hour intervals, usually in the morning and evening.
It is recommended that if Periostat® (doxycycline hyclate) is taken close to meal
times, allow at least one hour prior to or two hours after meals. Safety beyond 12
months and efficacy beyond 9 months have not been established.

82
DOXYCYCLINE TOPICAL
● Brand names: Atridox
Drug class(es): mouth and throat products
Doxycycline topical is used in the treatment of: Periodontitis
MULTI-INGREDIENT MEDICATIONS
CONTAINING DOXYCYCLINE:
doxycycline/omega-3 polyunsaturated fatty acids systemic
● Brand names: NutriDox Convenience Kit
doxycycline/salicylic acid topical
● Brand names: Avidoxy DK

83
MINOCYCLINE
● Minocycline, sold under the brand name Minocin among others, is a
tetracycline antibiotic medication used to treat a number of bacterial
infections such as pneumonia. It is generally less preferred than the
tetracycline doxycycline. It is also used for the treatment of acne and
rheumatoid arthritis.
● Taking it together with food, including milk, has no relevant influence on
resorption. It reaches highest blood plasma concentrations after one to two
hours and has a plasma protein binding of 70–75%. The substance
penetrates into almost all tissues;

84
Cynomycin 100 Capsule
● MANUFACTURER =Pfizer Ltd
● SALT COMPOSITION=Minocycline (100mg)
It is effective in some infections of the lungs, urinary tract, eyes, and others. It may
also be used for the treatment of severe acne.
● SUBSTITUTES= Syno 100mg Capsule, Minopride 100mg Capsule, Minotag
100mg Capsule

85
BETA-LACTAM ANTIBIOTICS
● include penicillins, cephalosporins, carbapenems and monobactams. All of
them have a -lactam ring in their chemical structure ,hence the name -lactam
antibiotics.
● Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the
bacterial organism and are the most widely used group of antibiotics
● The first β-lactam antibiotic discovered, penicillin, was isolated from a strain of
Penicillium rubens (named as Penicillium notatum at the time).
● Bacteria often develop resistance to β-lactam antibiotics by synthesizing a β-
lactamase, an enzyme that attacks the β-lactam ring. To overcome this
resistance, β-lactam antibiotics can be given with β-lactamase inhibitors such
as clavulanic acid.

86
PENICILLIN
● Penicillins are a group of antibiotics originally obtained from Penicillium
moulds, principally P. chrysogenum and P. rubens. Most penicillins in clinical use
are chemically synthesised from naturally-produced penicillins.
● only two purified compounds are in clinical use: penicillin G (intramuscular or
intravenous use) and penicillin V (given by mouth).
● Penicillins were among the first medications to be effective against many
bacterial infections caused by staphylococci and streptococci.

89
MECHANISM OF ACTION:
● Interferes with the synthesis of bacterial cell
wall.
The action of penicillin requires the presence of a cell
wall that contains peptidoglycans.

90
SYNTHESIS OF PEPTIDOGLYCAN
addition of 5 amino acids to N-acetyl muramic acid
Most gram positive bacteria do
not possess a periplasmic
space but have only periplasm
where metabolic digestion
occurs and new cell
peptidoglycan is attached.

91
Next, N-acetyl glucosamine is added to the N-acetyl
muramic acid to form a precursor of peptidoglycan.
This peptidoglycan precursor is then transported across the cell
membrane to a cell wall acceptor in the periplasm. Once in the
periplasm, the peptidoglycan precursors bind to cell wall
acceptors, and undergo extensive crosslinking.

92
Two major enzymes are involved in crosslinking: transpeptidase
and D-alanyl carboxypeptidase. These enzymes are also known as
penicillin binding proteins because of their ability to bind penicillins
and cephalosporins.
several layers of peptidoglycan are formed all of which are
crosslinked to create the cell wall. Gram positive bacteria have many
more layers than gram negative bacteria and thus have a much

93
Beta-lactam antibiotics include all penicillins and cephalosporins that
contain a chemical structure called a beta-lactam ring. This structure is
capable of binding to the enzymes that cross-link peptidoglycans. Beta-
lactams interfere with cross-linking by binding to transpeptidase and D-
alanyl carboxypeptidase enzymes, thus preventing bacterial cell wall
synthesis.

94
PENICILLIN-G (BENZYL/CRYSTALLINE PENICILLIN)
● It is a narrow spectrum antibiotic , activity is limited to gram
positive bacteria & few others.
■ Penicillin G is acid liable- destroyed by gastric acid when given
orally.Therefore,usually given by iv route.
■ Absorption from i.m site is rapid and but painful.
■ It is distributed mainly extracellularly; reaches most body fluids but
penetration in serous cavities and CSF is poor
■ It is little metabolized because of rapid excretion
■ t1/2 of penicillin in healthy adult is 30 min.
■ Action can be prolonged by giving probenecid simultaneously.

95
Adverse effects
■ Penicillin G is one of the most non toxic antibiotics.
■ Local irritancy- Pain at i.m injection site, Nausea on oral
injections, Thrombophlebitis of injected veins.
■ Hypersensitivity: Rash, Itching, Urticaria, Fever,
Wheezing, Anaphylaxis
■ Superinfection: Rare because of its narrow spectrum

96
Jarisch – Herxheimer reaction:
acute exacerbation of signs and symptoms of syphilis during penicillin
therapy due to release of endotoxins from the dead organisms.
Penicillin injected in a syphilitic patient may produce shivering, fever,
• myalgia, exacerbation of lesion and even vascular collapse.
• This is due to the sudden release of spirochetal lytic products and lasts 12-
72 hours.
• Aspirin and sedation for relief of symptoms.

97
Therapeutic Uses:
■ Dental infections :
• Periodontal abscess
• Periapical abscess
• Pericoronitis
• Necrotizing ulcerative gingivitis
• Oral cellulitis
■ Streptococcal infections :
• Pharyngitis
• Otitis media
• Scarlet fever
 Pneumococcal infections :
● Pneumonia
 Meningococcal infections
• Meningitis
• Diphtheria, Tetanus
• Prophylactic use
• Rheumatic fever
• Gonorrhoea
• Infective endocarditis
• Surgical infections

98
SEMISYNTHETIC PENICILLINS
■ Semisynthetic penicillins are produced by chemically combining
specific side chains.
■ This is to overcome the short comings of natural penicillin such as:
 Poor oral efficacy
 Susceptibility to penicillinase
 Narrow spectrum of activity
 Hypersensitivity

99
CLASSIFICATION:
ACID RESISTANT PENICILLIN
 Phenoxymethyl penicillin (penicillin V)
 PENICILLINASE RESISTANT PENICILLIN:
 Methicillin
 Oxacillin
 Cloxacillin
 EXTENDED SPECTRUM PENICILLINS
 Aminopenicillins: Ampicillin, Amoxicillin
 Carboxypenicillins: Ticarcillin
 Ureidopenicillins: Mezlocillin, Piperacillin
 Mecillinam (Amdinocillin)
 β LACTAMASE INHIBITORS:
 Clavulanic acid and sulbactam

101
AMPICILLIN
Ampicillin can be administered by mouth, an intramuscular injection (shot) or
by intravenous infusion.
Ampilin 250 MG Tablet
● Manufactured By :Hetero Healthcare Ltd
● Substitutes:Synthocillin 500mg Capsule,Neocillin 500mg Capsule,Ampurin
500mg Capsule,Mahacillin 500mg Capsule
● Uses : UTI , RTI, Meningits, Gonorrhoea
● Interactions : Hydrocotisone inactivates ampicillin mixed in IV

102
AMOXICILLIN
Amoxicillin (α-amino-p-hydroxybenzyl penicillin) is a semisynthetic derivative of
penicillin with a structure similar to ampicillin but with better absorption when taken
by mouth, thus yielding higher concentrations in blood and in urine.Amoxicillin diffuses
easily into tissues and body fluids.
Novamox 500 Capsule
● MANUFACTURER:Cipla Ltd
● SALT COMPOSITION: Amoxycillin (500mg)
● SUBSTITUTES: Moxilium 500mg Capsule,Radimox 500mg Caps
● Novamox 500 Capsule helps to eliminate a bacteria known as H. pylori in people
with peptic ulcer disease. It is a broad-spectrum antibiotic that fights and stops the
growth of many types of bacteria. This medicine is best taken with a meal to
reduce the chance of a stomach upset.

103
BETA – LACTAMASE INHIBITORS
• Beta-lactamases are a family of enzymes produced by many gram
positive and gram negative bacteria that inactivate the beta-lactam
antibiotics by opening the beta-lactam ring.
• They structurally resemble -lactam molecules. Beta-lactamase inhibitors
bind to lactamases and inactivate them. Coadministration of these drugs
with -lactams increases the activity of -lactams by preventing them from
enzymatic destruction.
● CLAVULANIC ACID, SULBACTAM AND TAZOBACTAM

104
CLAVULANIC ACID
■ Obtained from Streptomyces clavuligerus.
■ It inhibits a wide variety of beta-lactamases produced by both
gram positive and gram negative bacteria.
■ Also called ‘suicide inhibitor’ as it gets inactivated after binding
to the enzyme.

105
● Uses:
• Addition of clavulanic acid reestablishes the activity of amoxicillin against beta-
lactamase producing bacteria.
• Coamoxiclav (Amoxicillin + clavulanic acid) is indicated for :
• Skin and soft tissue infections,Gonorrhoea
• Urinary, Biliary, Respiratory tract infections
• Dental infections caused by β – lactamase producing bacteria.
• Dose: Amoxicillin 250mg + clavulanic acid 125mg tab; TDS, severe
infections 4 tabs 6 hourly.

106
Coamoxiclav (Amoxicillin + clavulanic acid)
• SUBSTITUTES:augmentin,moxclav,amonate
• USES:Skin and soft tissue infections,Urinary, Biliary, Respiratory
tract infections ,Gonorrhoea, Dental infections caused by β –
lactamase producing bacteria.
• Dose: Amoxicillin 250mg + clavulanic acid 125mg tab; TDS, severe
infections 4 tabs 6 hourly.
● Amoxicillin/clavulanic acid is the International Nonproprietary
Name (INN) and co-amoxiclav is the British Approved Name (BAN).

107
CEPHALOSPORINS
• These are group of semisynthetic antibiotics derived from
`Cephalosporin-C’ obtained from a fungus Cephalosporium.
• All cephalosporins are bactericidal and have the same mechanism of
action as penicillin.
• Penicillins are superior to these in their range of action against
periodontal pathogenic bacteria.
• Rashes, Urticaria, Fever and GI upset have been associated with
cephalosporins.
●

108
1st GENERATION 2nd GENERATION 3rd GENERATION 4th
GENERATION
5th GENERATION
ORAL ORAL ORAL ORAL ORAL
• CEFADROXIL
• CEPHALEXIN
• CEFACLOR
• CEFUROXIME
• CEFIXIME …….. ……….
PARENTERAL PARENTERAL PARENTERAL PARENTERAL PARENTERAL
• CEFAZOLIN
• CEPHALOTHIN
• CEFUROXIME
• CEFOXITIN
• CEFTRIAXONE
• CEFOPERAZNE
• CEFOTAXIME
• CEFEPIME
• CEFPIROME
• CEFTOBIPROLE
• CEFTAROLINE
• CEFTOLOZANE

109
Adverse effects :
○ Local irritancy
○ Diarrhoea
○ Hypersensitivity reactions
○ Nephrotoxicity
○ Neutropenia (rare)
Cefadrox 500mg Tablet
● MANUFACTURER: Aristo Pharmaceuticals Pvt Ltd
● SALT COMPOSITION: Cefadroxil (500mg)
● SUBSTITUTES: Adrocef, Aroxil,Codroxil 500mg Tablet

110
METRONIDAZOLE
■ Nitroimidazole compound developed in France to treat
protozoal infections
■ Bactericidal to anaerobic microoganisms .
■ Permeable through the bacterial cell wall, the drug binds DNA
and disrupts the helical structure. Breakage of the DNA strands
follows leading to cell death
■ It enters the cell by diffusion, where its nitro group is
converted into a highly reactive nitro radical which exerts
cytotoxicity.

111
• Plasma t1/2 is 8hrs
• Effective against A. actinomycetemcomitans when used in
combination with other antibiotics
• Also effective against anaerobes such as Porphyromonas
gingivalis and Prevotella intermedia.
Metrogyl 400 Tablet
● MANUFACTURER= J B Chemicals and Pharmaceuticals Ltd
● SALT COMPOSITION= Metronidazole (400mg)
● SUBSTITUTES= Metropen 400mg,metrogyl 400mg tab

112
Adverse Effects:
• Most Common=Nausea, Metallic taste, Abdominal cramps
• Less Frequent=Headache, Glossitis, Dryness of mouth and
dizziness
• Prolonged Administration=Peripheral Neuropathy and CNSa

113
Contraindications :
• Chronic alcoholics
• First trimester of pregnancy
• Neurological disease
• Blood dyscrasias
● Interactions:
• A Disulfiram-like intolerance to alcohol occurs in some
patients.
• Avoided for patients on anticoagulant therapy

114
USES IN PERIODONTICS
• It has been used to treat Gingivitis, ANUG, Chronic periodontitis,
and Aggressive periodontitis.
• Has been used in monotherapy as well as in combination with
scaling and root planing and with other antibiotics.
• A single dose of metronidazole 250 mg orally appear both in serum
and GCF in sufficient quantities to inhibit a wide range of suspected
periodontal pathogens.

115
● Administered systemically 750-1000 mg/day for 2 weeks, it reduces the
growth of anaerobic flora, including spirochaetes, and decreases the
histopathologic signs of periodontitis.
● Most common regimen is 250 mg t.i.d for 8 days.
● Metronidazole used as supplement to rigorous scaling and root planing
resulted in the reduced need for surgery compared with root planing
alone.
● It offers some benefit in the treatment of refractory periodontitis,
particularly when used in combination with amoxicillin.

116
FLUOROQUINOLONES
● The first quinolone, nalidixic acid, is a urinary antiseptic.
● Fluoroquinolones are synthetic fl uorinated analogues of nalidixic acid. The
important fluoroquinolones are norfl oxacin, ciprofl oxacin, pefloxacin, ofl
oxacin, levofl oxacin, gemifl oxacin and moxifl oxacin.

117
1st
GENERATION
2nd
GENERATION 3rd
GENERATION
4th
GENERATION
NALIDIXIC
ACID
CINOXACIN
CIPROFLOXACIN
NORFLOXACIN
OFLOXACIN
GATIFLOXACI
LEVOFLOXACIN
MOXIFLOXACIN
SITAFLOXACIN
TROVAFLOXACIN

118
Pharmacokinetics :
• Rapidly absorbed orally, but food delays absorption and first pass
metabolism occurs.
• The most prominent feature is High tissue penetrability, Concentration
in lung, sputum, muscle, bone, prostrate and phagocytes exceeds that
in plasma, but CSF and aqueous levels are lower.
• It is excreted primarily in urine, both by glomerular filtration and
tubular secretion.

119
● Urinary and Biliary concentrations are 10-50 fold that in plasma.
● t ½ 3 - 5 hrs
● Dose 250 - 750 mg b.i.d orally, 100 - 200 mg i.v
● Uses :
• Typhoid
• Bone & soft tissue infections
• Respiratory infections
• Urinary tract infections
• Tuberculosis
• Conjunctivitis

120
● In Periodontics :
• It demonstrates minimal effect on streptococcus species, associated with
periodontal health, it may facilitate the establishment of a microflora
associated with periodontal health.
• At present ciprofloxacin is the only antibiotic in periodontal therapy to which
all strains of aggregatibacter actinomycetemcomitans are susceptible.
• It has been used in combination with metronidazole.

121
● Adverse effects :
■ Gastrointestinal : Nausea, Vomiting, Bad Taste
■ CNS: Dizziness, Headache, Restlessness, Anxiety, Insomnia,
Impairment Of Concentration, Dexterity, Tremors And Seizures
(rarely)
■ Skin and Hypersensitivity: Rash, Pruritus, Photosensitivity,
Urticaria, Swelling Of Lips etc
■ Tendonitis and Tendon Rupture
■ Cartilage damage in weight bearing joints in children

122
MACROLIDE ANTIBIOTICS
● ERYTHROMYCIN
• Erythromycin is the first member discovered in the 1950s
• It was isolated from Streptomyces erythreus.
• Later additions - Roxithromycin, Azithromycin,
Clarithromycin
• Used as an alternative to penicillin.

123
MECHANISM OF ACTION :
■ Bacteriostatic at low and cidal at high concentrations.
■ They act by inhibiting protein synthesis.
■ They bind to 50S ribosomes and interferes with translocation.
■ They are active against mostly gram positive and a few gram
negative bacteria.
■ It is several fold more active in the alkaline medium, because the
nonionized form of the drug is favoured at higher pH.

124
Pharmacokinetics :
• It is acid labile.
• To protect it from gastric acid, it is given as enteric coated tablets,
from which absorption is incomplete and food delays absorption by
retarding gastric emptying.
• It is widely distributed in the body, enters cells and into abscesses,
crosses serous membrane and placenta, but not blood brain barrier.
• Excreted primarily in bile in the active form.
• Renal excretion minor, dose need not be altered in renal failure.

125
• The plasma t ½ is 1.5 hrs , but it persists longer in tissues.
• Dose: 250 - 500 mg tab 6 hourly (max. 4 g / day)
■ Children 30 - 60 mg/ kg/ day
● ERYTHROCIN, ERYSTER
• Uses :
■ Drug of choice
 Atypical pneumonia
 Pharyngitis
 Tonsillitis
 Respiratory / ENT infections

126
● In Periodontics :
■ Periodontal / periapical abscesses
■ Necrotizing ulcerative gingivitis
■ Post extraction infections.
● Adverse effects :
■ Epigastric pain
■ Diarrhoea
■ High doses - reversible hearing impairment
■ Hypersensitivity

127
AZITHROMYCIN
• This macrolide drug has expanded spectrum, improved
pharmacokinetics, better tolerability and drug interaction profiles.
• High activity against respiratory pathogens.
• Acid stable
• Rapid oral absorption
• Marked tissue distribution
• Intracellular penetration.
○ AZITHRAL, AZIWOK 250, 500 mg cap

128
● Major advantage :
• Convenient dosing : 500 mg od for 3 days or 500 mg initial loading dose
followed by 250 mg od for 4 days
• Concentration in most tissues exceed that in plasma particularly higher
concentrations are attained in macrophages and fibroblasts.
• Slow release from intracellular sites contributes to its long terminal t ½ > 50
hrs.
● Adverse effects:
• Mild gastric upset, Abdominal pain (less than erythromycin)
• Headache, Dizziness

129
CLINDAMYCIN
■ A lincosamide antibiotic similar in mechanism of action and
spectrum of activity to erythromycin, with which it exhibits partial
cross resistance.
■ Bacteriostatic drug.
■ Effective against anaerobic bacteria.
■ Used when patient allergic to penicillin.
■ Oral absorption good.

130
• Penetrates into most skeletal and soft tissues, but not to brain and
CSF; accumulates in neutrophils and macrophages.
• Is largely metabolized and metabolites are excreted in urine and bile.
• t ½ is 3 hrs.
○ DALCAP, DALCIN, CLINCIN – 150, 300 mg cap. QID
• Mechanism of action :
○ Inhibits protein synthesis by binding to 50S ribosomal
subunit and interferes with translocation.

131
Adverse effects :
■ Rashes
■ Urticaria
■ Abdominal pain
■ Major problems – Diarrhoea and
Pseudomembranous enterocolitis (Metronidazole
alternatively Vancomycin given to treat it )

132
DRUG INTERACTIONS
1. PENICILLINS :
 Efficacy decreased by tetracyclines, erythromycin and cephalosporins
 Potentiates anticoagulant effects of warfarin and aspirin
2. ERYTHROMYCIN :
 Potentiates vasoconstrictive effects of ergot alkaloids
 Potentiates toxicity of theophylline
3. TETRACYCLINES :
 Potentiates anticoagulant effects of warfarin
 Potentiates nephrotoxicity of diuretics
 Decreases bacteriocidal effects of penicillins and ciprofloxacin
 Digestive absorption inhibited by antacids, antianemics, magnesium-
containing drugs and milk product

133
● 4. METRONIDAZOLE :
 Potentiates anticoagulant effects of coumadin (warfarin)
 Alcohol consumption and disulfiram elicit “antabuse reaction” (abdominal cramps,
nausea, vomiting, headaches, toxic psychosis)
 Potentiated by chloramphenicol and cimetidine
 Potentiates phenytoin and phenobarbital
● 5. CIPROFLOXACIN :
 Potentiates toxicity of theophylline
 Digestive absorption inhibited by antacids
 Reduces metabolism of caffeine
 Enhances effect of warfarin
● 6. CEPHALEXIN :
 Potentiates anticoagulant effects of coumadin (warfarin) and aspirin
 Bacteriocidal effects decreased by tetracyclines and erythromycin

135
SUBGINGIVAL METRONIDAZOLE
● Elyzo 25% Dentalgel (EDG) which is developed for use in the treatment
of periodontitis is a suspension of metronidazole benzoate (40%) in a
mixture of glyceryl mono-oleate (GMO) and triglyceride (sesame oil).
Metronidazole can be detected in the periodontal pockets 24-36 h after
application. It is 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.
● As a precursor, the preparation contains metronidazole benzoate, which
is converted into the active substance by esterases in GCF.

136
● TETRACYCLINE CONTAINING FIBRES (ACTISITE)
○ Actisite® (tetracycline periodontal) periodontal fiber for periodontal
pocket placement consists of a 23 cm (9 inch) monofilament of
ethylene/vinyl acetate copolymer, 0.5 mm in diameter, containing 12.7
mg of evenly dispersed tetracycline hydrochloride, USP.Actisite®
(tetracycline periodontal) fiber provides continuous release of
tetracycline for 10 days.

137
SUBGINGIVAL MINOCYCLINE (ARESTIN)
● ARESTIN (minocycline hydrochloride) microspheres, 1mg is a subgingival
sustained-release product containing the antibiotic minocycline
hydrochloride incorporated into a bioresorbable polymer, Poly (glycolide-co-
dl-lactide) or PGLA, for professional subgingival administration into
periodontal pockets. Each unit-dose cartridge delivers minocycline
hydrochloride equivalent to 1 mg of minocycline free base.2% minocycline
is encapsulated into bioresorbable microspheres in a gel carrier.

138
DOXYCYCLINE (ATRIDOX)
● The ATRIDOX (doxycycline hyclate) ® product is a subgingival controlled-release product composed
of a two syringe mixing system.
● Syringe A contains 450 mg of the ATRIGEL® Delivery System, which is a bioabsorbable, flowable
polymeric formulation composed of 36.7% poly(DLlactide) (PLA) dissolved in 63.3% N-methyl-2-
pyrrolidone (NMP).
● Syringe B contains 50 mg of doxycycline hyclate which is equivalent to 42.5 mg doxycycline. The
constituted product is a pale yellow to yellow viscous liquid with a concentration of 10% of
doxycycline hyclate. Upon contact with the crevicular fluid, the liquid product solidifies and then
allows for controlled release of drug for a period of 7 days.

139
SUBGINGIVAL MINOCYCLINE (ARESTIN)
● ARESTIN (minocycline hydrochloride) microspheres, 1mg is a subgingival
sustained-release product containing the antibiotic minocycline
hydrochloride incorporated into a bioresorbable polymer, Poly (glycolide-co-
dl-lactide) or PGLA, for professional subgingival administration into
periodontal pockets. Each unit-dose cartridge delivers minocycline
hydrochloride equivalent to 1 mg of minocycline free base.2% minocycline
is encapsulated into bioresorbable microspheres in a gel carrier.

140
IRRIGATION WITH ANTIBIOTICS
● 10% TETRACYCLINE HCL
● As per Silverstein et al.8 when a waterpik is used to deliver tetracycline subgingivally, an
increased levels of tetracycline is obtained within gingival crevicular fluid and these levels
are more than that achieved with antibiotics administered systemically.
● Additionally, tetracycline has been shown to be efficacious against the periodontal
diseasecausing pathogenic microorganisms, by increasing the attachment of fibroblasts to
fibronectin-associated dental structures and by inhibiting the activity of collagenase.

141
COMMON ANTIBIOTIC THERAPIES IN THE
TREATMENT OF PERIODONTAL DISEASES
● Amoxicillin - 500 mg / t.i.d / 5 days
● Metronidazole - 400 mg / t.i.d / 8
days
● Clindamycin - 300 mg / t.i.d / 10 days
● Doxycycline or minocycline - 100 - 200 mg/ o.d /21days
● Ciprofloxacin - 500 mg / b.i.d / 8 days
● Azithromycin - 500 mg / o.d / 4 - 7 days
● Combination Therapy :
■ Metronidazole + Amoxicillin - 250 mg of each drug / t.i.d / 8 days
■ Metronidazole + Ciprofloxacin - 500 mg of each drug / b.i.d / 8 days

142
NECROTISING ULCERATIVE GINGIVITIS
○ Amoxicillin 500 mg every 6 hours for 10 days
● For amoxicillin sensitive patients
○ Erythromycin -500 mg every 6 hours
○ Metronidazole – 500 mg bid for 7 days

143
ACUTE PERICORONITIS
● Antibiotics are advised in severe cases and in patients who may have
clinical evidence of diffuse microbial infiltration of the tissue
○ Amoxcillin 500 mg + metronidazole 400mg tid for 5 days
○ Ornidazole 500 mg + ofloxacilin 200 mg bid for 5 days

144
ACUTE HERPETIC GINGIVOSTOMATITIS
○ Earlier consisted of palliative therapy
○ Can give antiviral therapy (acyclovir )
○ 15 mg/kg of an acyclovir suspension given five times daily for 7
days.

145
ACUTE PERIODONTALABSCESS
 Amoxicillin:
■ Loading dose of 1.0 g followed by a maintenance dose of 500
mg/t.i.d. for 3 days
■ revaluation
 Allergy to ß-lactam drugs
■ Azithromycin: loading dose of 1.0 g on day 1, followed by 500 mg
od for 3 days OR
■ Clindamycin: loading dose of 600 mg on day 1, followed by 300
mg/q.i.d. for 3 days

146
AGGRESSIVE PERIODONTITIS
○ Systemic tetracycline -250 mg qid for atleast 1 week should be
given in conjuction with mechanical debridement.
○ Doxycycline -100 mg od may be used instead of tetracycline.

147
FAILURES OF ANTIBIOTIC THERAPY
● Inappropriate choice
● Antibiotic resistance
microorganisms
● Low blood concentration
● Growth rate of microorganisms
● Impaired host defense
● Non compliance
● Antagonism
● Lack of penetration
● Decreased blood flow
● Local factors
● Source of infection

148
CONCLUSION
 Antibiotics are powerful medicines that fight certain
infections and can save lives when used properly. They are
valuable and in some instances life-saving drugs. They can
only retain this position in medicine and dentistry if used with
care and prescribed appropriately.

149
REFERENCES :
● Essentials of medical pharmacology- K D Tripathi - 7th edition
● Carranza’s Clinical Periodontology - Newman, Takei, Klokkevold, Carranza- 10th
edition
● Antibiotic/Antimicrobial use in Dental practice - Michael Newman, Kenneth
Kornman
● Antibiotics in periodontal therapy advantages and disadvantages Slots and
Rams J Clin Periodontol l990; 17: 479-493.
● Systemic & topical antimicrobial therapy in Periodontics Periodontology 2000;
1996, vol 10
● Systemic antibiotics in the treatment of periodontal disease Periodontology
2000, Vol. 28, 2002, 106–176

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