ANTIBIOTICS

ONTENTS
Introduction
Classifications
Characteristics of an ideal antibiotic
Antibiotic selection
Problems associated with antibiotics usage
-lactam antibiotics
Tetracyclines

Nitroimidazole derivatives
Aminoglycosides
Macrolides
Quinolones
Use of antibiotics in endodontics
Antibiotics in pregnancy
Antibiotics in lactating women
Antibiotics in renal and hepatic dysfunction
Antibiotic prophylaxis
Conclusion
References

INTRODUCTION

Drug : drug is any substance / product that is used / is
intended to be used to modify / explore physiological
systems / pathological states for the benefit of one
recipient.
Chemotherapy : it is the treatment of systemic infection /
malignancy with specific drugs that have selective toxicity
for the infecting organism / malignant cell with no /
minimal effects on the host cells.

INTRODUCTION

Antibiotics
These are the substance produced by the
microorganisms which suppress the growth of or kill
microorganisms at very low concentration.

Antibiotic (Greek-anti means against and biosis means
life).




Initially term chemotherapeutic agent was used
synthetic compounds.

Now both synthetic & microbiologically produced drugs
need to be included

Hence the term antimicrobial agent.
CLASSIFICATION OF ANTIBIOTICS
Mechanism
Of action
Organisms
susceptible
Chemical
structure
Spectrum
of activity.
Type of
action.
Mechanism of action
ORGANISMS SUSCEPTIBLE

Antiprotozoal
Chloroquine
Pyrimethamine
Metronidazole
Diloxanide
Antifungal
Griseofulvin
Amphotericin B
Ketoconazole
Antibacterial
Penicillins
Aminoglycosides
Erythromycin etc
Anthelmintic
Mebendazole
Pyrantel
Niclosamide
Diethyl carbamazine
Antiviral
Idoxuridine
Acyclovir
Zidovudine
PECTRUM OF ACTIVITY

Narrow
spectrum
Penicillin G
Streptomycin
Erythromycin
Broad
spectrum
Tetracyclines
Chloramphenicol
CHEMICAL STRUCTURE

1. Sulfonamides and related drugs
Sulfadiazine and others
Sulfones Dapsone (DDS),
Paraaminosalicylic acid (PAS).
2. Diaminopyrimidines
Trimethoprim
Pyrimethamine
3. Quinolones
Nalidixic acid Ciprofloxacin
Norfloxacin
4. Tetracycline's
Oxytetracycline
Doxycycline etc
5. Nitrobenzene derivative
Chloramphenicol
6. -lactam antibiotics
Penicillins
Cephalosporins
Monobactams
Carbapenems

7. Aminoglycosides
Streptomycin
Gentamicin
Neomycin etc
8. Macrolide antibiotics
Erythromycin
Roxithromycin
Azithromycin etc
9. Polypeptide antibiotics
Polymyxin-B
Colistin
Bacitracin

10. Glycopeptides
Vancomycin
Teicoplanin
11. Oxazolidinone
Linezolid
12. Nitrofuran derivatives
Nitrofurantoin
Furazolidone
13. Nitroimidozoles
Metronidozole
Tinidazole

14. Nicotinic acid derivatives
Isoniazid
Pyrazinamide
Ethionamide
15. Polyene antibiotics
Nystatin
Amphotericin-B
Hamycin
16. Azole derivatives
Miconazole
Clotrimazole
Ketoconazole

17. Others
Rifampin
Lincomycin
Clindamycin
Spectinomycin
Sod. fusidate
Cycloserine
Viomycin
Griseofulvin

TYPE OF ACTION
Primarily
bacteriostatic
Sulfonamides
Tetracyclines
Chloramphenicol
Erythromycin
Ethambutol
Primarily
bactericidal
Penicillins
Aminoglycosides
Cotrimoxazole
Cephalosporins
Vancomycin Ciprofloxacin
ANTIBIOTICS ARE OBTAINED FROM
Fungi
Penicillin
Cephalosporin
Griseofulvin

Bacteria
Polymyxin B
Colistin
Bacitracin
Tyrothricin
Actinomycetes
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Polyenes
CHARACTERISTICS OF AN IDEAL
ANTIBIOTIC
Site of infection.
Should not cause the development of resistance
Undesirable side effects
Orally without inactivation by stomach acid, or
parenterally without binding to the blood proteins
Concentrations in the tissue or blood, sufficiently high
to inhibit or kill the infectious agent.

FACTORS GOVERNING ANTIBIOTIC
SELECTION


Pharmacokinetic
factors
Organisms
related
Host factors
PROBLEMS ASSOCIATED WITH
ANTIBIOTIC USE
Toxicity
Drug
Resistance
Nutritional
Deficiencies
Superinfection
Hypersensitivity
Reactions
PENICILLINS
First antibiotic to be used clinically
Discovery
+ 1928 Alexander Fleming ,
St. Marys hospital
London
Penicillium notatum
Penicillium chrysogenum
Thiazolidine + beta lactum rings to which side chains are attached
This side chain can be split off
Other side chains then attached- Semi-synthetic Penicillins
CLASSIFICATION OF PENICILLINS
1. Natural penicillin
Penicillin G (benzyl penicillin)
Procaine penicillin G
Benzathine penicillin G
2. Acid resistant penicillin
Phenoxymethyl penicillin (penicillin V)
Phenoxyethylpenicillin (phenethecillin)
3. Penicillianse resistant penicillins
Acid labile methecillin, nafcillin, cloxacillin,
dicloxacillin
Acid resistant flucloxacillin
4. Penicillins effective against gram positive and some
gram-negative organisms
Ampicillin
Amoxycillin
Talampicillin
5. Extended spectrum penicillins
Aminopenicillins Ampicillin Amoxycillin
Carboxypenicillins carbenicillin, ticarcillin
Ureidopenicillins piperacillin, mezlocillin
Amidino penicillins mecillinam, pivmecillinam
6. Penicillins with betalactamase inhibitors
Amoxycillin clavulanic acid (Augmentin)


BENZYL PENICILLIN (PENCILLIN G)
PnG - narrow spectrum antibiotic; activity is limited
primarily to gram positive bacteria
Is available in the form of water soluble sodium and
potassium salts
Most potent AMA, inhibits the growth of susceptible
organism.
Mainly gram +ve, gram ve cocci and some gram +ve
bacilli with exception of enterococci.

MECHANISM OF ACTION
Bactericidal drug effective mainly against
multiplying organisms.
Penicillin requires cell wall that contains
peptidoglycans
Peptidoglycans is heteropolymeric component
of cell wall provides rigid mechanical, cross
linked lattice like structure. .
Penicillins bind to these proteins and inactivate
them, thereby preventing the synthesis and
cross linkage
This weakens bacterial cell wall and makes
organism vulnerable to damage.
Peptidoglycan
Exposure to beta lactum antibiotics
Weak points lacking
peptidoglycan
Exposure to hypotonic environment
Membrane bulges out as
water
Diffuses into coil
Membrane breaks
Cell lyses
Absorption fate and excretion :
About 1/3 of drug is activated on oral administration.
Absorbed from the duodenum.
Because of the inadequate absorption the oral dose
should be 4/5 times larger than the intramuscular
dose.
As food interferes with its absorption PnG should be
given orally at least 30 min after food or 2 to 3 hours
before food.
Penicillin in aqueous solution is rapidly absorbed
after SC or IM administration.
Peak plasma level of 8 to 10 units per ml is reached
with in 15 to 30 min and drug disappears from plasma
with in 3-6 hours.

Preparation and dose :
PnG inj 0.5-5 MU i.m or i.v 6-12 hours
Procaine penicillin inj 0.5, 1 MU dry powder in vial

Use in endodontics

Penicillin V antibiotic of choice

Effective against both facultative and anaerobic
organisms found in polymicrobial endodontic
infections

Loading dose 1000mg followed by 500mg 4-6 hrs
SEMI SYNTHETIC PENICILLINS

The major drawbacks of benzyl penicillin are :
1. Inactivation by the gastric hydrochloric acid
2. Short duration of action
3. Poor penetration into CSF
4. Activity mainly against gram +ve organism
5. Possibility of anaphylaxis

The attachment of side chains are inhibited and instead
various organic radicals can be substituted.

Acid resistant penicillin :


1. Potassium phenoxymethyl penicillin (penicillin V)
Similar antibacterial spectrum like benzyl
penicillin.
More active against resistant staphylococci
Less inactivated by the gastric acid.
Plasma levels achieved is 2 to 5 times higher than
benzyl penicillin.
Available as 60 & 125 mg tablets..

2. Potassium phenoxyethyl penicillin and
3. Azidocillin
Both have similar properties to penicillin V and no
difference in the antibacterial effect

Extended spectrum penicillin's :
1. Amino penicillin's
1. Ampicillin
Antibacterial activity is similar to that of PnG that
is more effective than PnG against a variety of
gram-ve bacteria
Absorption, fate and excretion :
Oral absorption is incomplete but adequate
Food interferes with absorbtion
Dose : 0.5-2 gm oral/IM or IV depending on severity of
infection every 6 hours


Adverse effects :
Diarrhoea is frequent
Skin rashes is more common
Unabsorbed drug irritates lower intestines
Patient with history of hypersensitivity to PnG should
not be given Ampicillin.

AMOXYCILLIN
This is a semisynthetic penicillin
(amino-p-hydroxy-benzylpencillin)
Antibacterial spectrum is similar to ampicillin
Oral absorption is better; food does not interfere;
higher and more sustained blood levels are produced.
It is less protein bond and urinary excretion is higher
than that of ampicillin.
Incidence of diarrhoea is less

Dose : 0.25-1 g TDS oral

Adverse effects :
Pain - thrombophebitis
Rashes and Diarrhoea

Use in endodontics

Expanded spectrum that includes bacteria not
routinely associated with infections of endodontic
origin

Ideal for medically compromised patients requiring
antibiotic prophylaxis

Loading dose 1000 mg followed by 500mg - 8 hrs

Alternative dosage 875mg - 12 hrs
BETA LACTAMASE INHIBITORS


CLAVULANIC ACID

Streptomyces clavuligenus
Inhibits beta lactamases
(Gm+ve & Gm-ve)
Poor intrinsic antimicrobial activity
Progressive inhibitor / Suicide inhibitor
Rapid oral absorption
Used with Amoxycillin -
250 mg Amoxycillin + 125 mg Clavulanic acid

Clavulanic
acid
Amoxicillin Oral
Ticarcillin Parenteral
Use in endodontics

Excellent results against bacteria isolated from
endodontic infections (Augmentin)

Considered for immunocompromised patients

Loading dose 1000mg followed by 500mg 8 hrs

Alternative dosage 875 mg 12 hrs
SULBACTUM

Semi-synthetic Beta lactamase inhibitor

Sultamicillin tosylate-salt with Ampicillin

USES Mixed infections


II) Pencillinase resistant pencillins :


Methicillin
1. High penicillinase resistance
not acid resistance
2. IM or IV (slow) in the dose of
1 gm every 4-6 hours.
3. Hematuria, albuminurea and
reversible interstitial nephritis
are the special adverse effect
of methicillin.


Cloxacillin
1. Weaker antibacterial activity.
2. Oral dose for adults 2-4 gm
divided into 4 portions.
3. IM adults 2-12 gm/day,
children 100-300 mg/kg/day
every 4-6 hours.
Oxacillin, Dicloxacillin, Flucloxacillin are other
penicillins similar to cloxacillin, but not marketed in
India.


MECHANISM OF BACTERIAL RESISTANCE
High-molecular-weight Penicillin Binding Proteins.
Inability to penetrate to its site of action- target enzymes
& PBPs are located deeper under lipoprotein barrier.
o Production of Penicillinase - narrow spectrum -
lactamase opens lactam ring & inactivates PnG.
Gram +ve elaborates larger quantities of enzyme
Gram - ve elaborates in smaller quantities




Some bacteria penicillin tolerant-their target enzymes
altered & have low affinity for penicillin.
Gram ve have porin channels premeability differs
for various lactam antibioticssome gram ve
become resistant due to loss or alteration of porin
channels.

UNTOWARD REACTIONS TO PENICILLIN
Nausea ,diarrhoea
Thrombophlebitis
Hypersensitivity reactions(0.7 % - 10 %)
Serum sickness
Fever
Eosinophilia

QUINOLONES
Synthetic
Active mainly against Gram ve bacteria
1
st
generation fluoroquinolones introduced in 1980
having one fluoro substitution.
In 1990 compounds with additional fluoro & other
substitution have been developed further extending
antimicrobial activity & confering metabolic stability (
longer t
1/2
) these are 2
nd
generation fluoroquinolones.


NALIDIXIC ACID
Active against Gm-ve Bacteria
Bactericidal
Inhibits bacterial DNA Gyrase
Absorbed orally
Plasma half life is 8 hrs
Primarily used as urinary antiseptic , 2
nd
line of drug in
recurrent cases.



USES
1. Primarily used as urinary antiseptic , 2
nd
line of drug in
recurrent cases.
FLUOROQUINOLONES
Quinolones having one /more Fluorine substitutions


Ist Generation-1 Fluorine
Norfloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin

2
nd
Generation More
Fluorine & other substitution
Lomefloxacin
Sparfloxacin
Fleroxacin
Amikofloxacin

CIPROFLOXACIN
Most potent Ist gen FQ

Gm-ve bacilli

Rapid bactericidal & high potency

Long post-antibiotic effect

Low mutational resistance

Protective intestinal flora spared

Many B lactum & Aminoglycoside resistant
MECHANISM OF ACTION
Inhibit enzyme bacterial DNA gyrase- nicks double
stranded DNA, introduce negative supercoils-
reseals the nicked ends
PHARMACOKINETICS


ADVERSE EFFECTS


Rapid oral absorption
High tissue penetrability
Nausea,vomitting,anorexia
Dizziness,Insomnia,Anxiety,
confusion,tremors,Restlessness
Hypersensitivity
Use in endodontics

Not effective against anaerobic bacteria that is
found in endodontic infections

Indicated if culture and sensitivity tests demonstrate
presence of susceptible organisms
NORFLOXACIN
Less potent
Primarily for UTI
PEFLOXACIN
Methyl derivative of Norfloxacin
More lipid soluble , better penetration

OFLOXACIN
Activity between Ciprofloxacin & Norfloxacin

SPARFLOXACIN
Recently introduced
Difluorinated
Enhanced activity against Gram-ve bacteria , Anaerobes
& Mycobacteria
High efficacy in Mycobacterium Avium infections in
AIDS patient
CEPHALOSPORINS
Semisynthetic derived from natural Cephalosporin-C
(fungus- Cephalosporium)
Chemically related to Penicillins
Bactericidal
Same mechanism of action as penicillins
Inhibit cell wall synthesis
CLASSIFICATION
1
st
Generation (1960s)
Parenteral Oral
Cefazolin Cephalexin
Cefadroxyl
Cephadrine
2
nd
Generation
Parenteral Oral
Cefuroxime Cefuroxime axetil
Cefaclor

Gram+ve
Oral cavity anaerobes
Gram-ve
3
rd
Generation (1980s)
Parenteral Oral
Cefotaxime Cefixime
Ceftazidime
Ceftriaxone
Ceftizoxime

4
th
Generation (1990s)
Parenteral
Cefpirome


Highly augmented against G
ve Enterobacteriae
High resistance to -lactamase
producing

Same abtibacterial spectrum
Increased stability to -lactamase
ADVERSE EFFECTS- CEPHALOSPORINS
More toxic than Penicillins
Pain after I.m injection
Hypersensitivity
Neutropenia, Thrombocytopenia
Disulfiram like reaction with alcohol
Nephrotoxicity
Bleeding
DRUG INTERACTION
Cephalosporins plus alcohol can cause Antabuse-like
effects,
Aspirin or heparin plus Cephalosporins can increase
bleeding risk
Use in endodontics

Not usually indicated
1
st
gen not effective against anaerobes involved in
endodontic infections
2
nd
gen some effect however possibility of cross
allerginicity with penicillin


TETRACYCLINES

Tetracyclines are napthacene derivatives.
The napthacene nucleus is
made up by fusion of 4 partially unsaturated
cyclohexane radicals and hence the name tetracyclines.
Tetracycline's are broad spectrum & bacteriostatic.

Chlortetracycline
Oxytetracycline
Natural
Tetracycline
Doxycycline
Minocycline
Semi-
synthetic
On the basis of chronology of development, convenience
of description, divided into 3 groups.

Group I Group II
Tetracycline Demeclocyline
Oxytetracycline Methacycline

Group III
Doxycycline
Minocycline
.

Mechanism of action :
Tetracyclines are thought to inhibit bacterial protein synthesis by
binding to the 30 S bacterial ribosome and preventing the access of
Aminoactyl RNA to the acceptor (A) sites on the mRNA ribosome
complex

Antimicrobial activity :
Gram +ve and ve cocci are sensitive
Gram +ve bacilli are inhibited
Oral Parenteral
Tetracycline 1-2 g/day
Doxycycline 200 mg of
1
st
loading dose,100
mg/day
Doxycycline 200mg then
100 mg
Minocycline 200 mg then
100 mg/12 hr
Minocycline 200mg then
100mg/12 hr

DOSE
Pharmacokinetics :
Incompletely absorbed from GIT
Absorption is impaired by iron or zinc salts
[due to chelation of cations]
They cross the placenta and enter fetal circulation and
amniotic fluid
Widely distributed in liver
,bone marrow and spleen
Enterohepatic circulation
Primarily excreted in urine through kidney

Adverse effects :
GIT- Epigastric burning, nausea, vomiting, Diarrhoea
Hepatoxicity
Renal toxicity
Effects on teeth-Orthophosphate complex
Thrombophlebitis
Hypersensitivity Reactions
Super infection

Precaution :
Not to be used in pregnancy, lactation and in children
Avoided in patients on diuretics
Used cautiously in renal and hepatic insufficiency
Do not mix Injectable Tc with Pn- inactivation
occurs


EFFECT ON TEETH & BONES

Calcium-Tetracycline chelate

Midpregnancy-5 mth of E/U life
Deciduous teeth affected

3 mth - 5 yrs
Permanent anterior dentition

Late pregnancy - childhood
Temporary suppression of bone growth.
Anti anabolic effect-reduce Protein synthesis
Increased intracranial pressure (infants)
Vestibular toxicity
Hypersensitivity
Superinfection most common antibiotic responsible

Use in endodontics

May be indicated when all the above antibiotics are
contraindicated

Many strains have become resistant
NITROIMIDAZOLES
Imidazole hetero cycles with a nitro group
Have been used to combat anaerobic bacterial and
parasitic infections.
Most common example is metronidazole
Diffuses into all tissues& body fluids
Cross CNS & placenta
Other drugs are :- Tinidazole, Secnidazole, Ornidazole
Satranidazole


METRONIDAZOLE
Almost complete absorption
Peak plasma con 8-13 g/ml within 0.25-4 hours
Wide distribution
High GCF and saliva concentration

MECHANISM OF ACTION
Prodrug

Reduction of the nitro group of the drug by redox proteins of
anaerobic org

Highly reactive Nitro radical produced

DNA helix destabilization & strand breakage


Death of the organism

CONTRAINDICATIONS
Neurological disease, blood dyscrasias
Pregnancy,chronic alcoholism (disulfiram like
intolerance)
Patients on enzyme inducer eg phenobarbitone &
rifampicin may reduce its therapeutic effect

Drug Metronidazol
e

Tinidazole Sacnidazole Ornidazole

Plasma half-
life
8hrs 12-16 hrs 17-29 hrs

12-14 hrs
Dosage 400 mg tds 0.5-1.0 g o.d 1 g od 500 mg bid
ADVERSE EFFECTS
Nausea , abdominal cramps , headache dry mouth,
metallic taste
Prolong therapy (CNS)
Thrombophlebitis
Disulfiram-like reaction- alcohol

DRUG INTERACTIONS
Alcohol
Cimetidine-metabolism increases
Enzyme inducers -Phenobarbital decreases.
anticoagulants
Synergic effect Spiramycin + Metronidazole
Carcinogenic

Use in endodontics

Valuable in combination with penicillin when
penicillin alone is ineffective

Loading dose 1000mg followed by 500mg 6 hrs
MACROLIDE
First discovered in 1950s
Macrocyclic lactone ring with attached sugar moiety
Erythromycin is the prototype drug
Roxithromycin, Clarithromycin & Azithromycin are
the later additions
Bacteriostatic at lower concentrations & bactericidal at
higher concentration
Aerobic gram positive cocci and bacilli

MECHANISM OF ACTION
Erythromycin binds
50S subunit of
bacterial ribosome
& inhibits protein
synthesis

PHARMACOKINETICS
Acid labile
Available as enteric coated tablets
Crosses serous membranes & placenta
Does not cross blood brain barrier
Plasma t is 1.5 hr
Partly metabolised & excreted in bile, small amount
excreted by kidneys

ADVERSE EFFECTS &DRUGINTERACTIONS
Fever, eosinophilia, skin eruptions
Nausea, vomiting, abdominal pain
Cholestatic hepatitis- Estolate
Potentiate effect of Carbamezapine, corticosteroids,
cyclosporine, digoxin, triazolam, warfarin
* drug interactions are shared by clarithromycin &
azithromycin

INDICATIONS & DOSAGE
Primary : Atypical Mycoplasma pneumonia, whooping
cough, chancroid
Alternative to Penicillin : Streptococcal pharyngitis,
tonsillitis, mastoiditis, Diphtheria, Tetanus & Syphilis
Second choice drug : Penicillin resistant Staph
infections,
DOSAGE
ERYTHROMYCIN

250- 500mg/6 hrly (maximum 4g/day)
ALTHROCIN 125, 250, 500mg tab or 250mg/5ml vial

AZITHROMYCIN

250-500 mg OD x 03 days


AZITHRAL, AZIWOK, AZIWIN 100, 250, 500 mg capsule
ROXITHROMYCIN
Semi synthetic, long acting, acid
stable
Plasma t 12 hrs
Respiratory, ENT, skin infection
ROXID, RULIDE 50, 150
,300 mg tab
Dose: 150-300 mg BID 30 mins
before meal
CLARITHROMYCIN
Same as Roxithromycin
Plasma t 3-6 to 6-9 hrs
URTI, LRTI , ENT, skin &
soft tissue infections
CLARIBID ,CLARIMAC
250, 500 mg
Dose : 250 - 500 mg BID x
07 days
Use in endodontics

Alternative choice for patients allergic to penicillin

Clarithromycin and Azithromycin adv over
erythromycin broader spectrum of activity
lesser GI upset

Loading dose 500mg

Followed by 250 mg - 12 hrs (Cl)
- 24 hrs (Az)

ANTIBIOTICS IN ENDODONTICS
Majority of infections without
antibiotics

Not a substitute for timely endodontics

Chemomechanical debridement of the canal ,
drainage through the canal / incision and drainage
bioburden healing
Lack of circulation systemically
administered antibiotics not effective against
reservoir of microorganisms

MIC may not reach the anatomic spaces filled with
purulence and edematous fluid
Conditions not requiring adjunctive antibiotics


- Pain without signs and syptoms
a. symptomatic irreversible pulpitis
b. symptomatic apical periodontitis
- Teeth with necrotic pulps and radiolucencies
- Teeth with sinus tract
- Localized fluctuant swellings
- Following endodontic surgery

Antibiotic regimen is prescribed in conjugation with
endodontic treatment when

- systemic signs and symptoms of infection

- Progressive persistent spread of infection
Indications for adjunctive antibiotics

Systemic involvement
Fever > 100
0
F
Lymphadenopathy
Trismus

Progressive infections
Increased swelling
Cellulitis
Osteomyelitis

Persistent infections
Administration of antibiotics

Loading dose provides initial adequate
therapeutic blood levels

Continued for 2 3 days following resolution of the
major signs and symptoms

7 day regimen is adequate
MEDICATIONS IN PREGNANCY.
In general, every medication is assigned to a
category (A,B, C, D, or X) based on how safe or
risky it is to use during pregnancy

Category A
that human studies have shown no evidence of
fetal harm in the first trimester or later in the
pregnancy.eg
Nystatin vaginal (Mycostatin)


Category B

Most antibiotics are Category B, which means that there is no
known association with birth defects or other pregnancy-related
complication and the drug is probably safe. These include:

Amoxicillin
Ampicillin
Augmentin
Dicloxicillin
Nitrofurantoin
Metronidazole (although there is some controversy about taking it
by mouth in the first trimester)
Cephalosporins
clindamycin
Erythromycin
Azithromycin
Sulfa Drugs (until near term)
Famciclovir
Acyclovir
Valacyclovir
Category C

Others are Category C, meaning that either there isn't
enough information or there are some concerns arising
from animal studies, but no confirmation of problems like
birth defects in humans. These include:

Bactrim,
Trimethoprim
Clarithromycin
Ciprofloxacin
Fluconazole
Miconazole
Terconazole
Isoniazid
Rifampin
Mebendazole
Tetanus Toxoid
Vaccines: hepatitis A, hepatitis B, influenza,
meningococcus, pneumonia (pneumococcus), polio

Category D
clear-cut problems in pregnancy and should not be used
unless there are no better alternatives.
These includes:


Tetracycline derivatives, which can cause discoloration of
teeth: tetracycline, doxycycline (Vibramycin), Minocin
(minocycline)

Sulfa drugs - if near delivery (increase the chance of serious
newborn jaundice)


ANTIBIOTICS IN BREAST FEEDING
Administration of drugs to women who are breast
feeding may have ill effects on the suckling infant
and or affect lactation

a. Antibiotics whos amount is too small to be harmful
to the infant / those found to be safe

- Cephalosporins

- Erythromycin


Drug Comment / possible side effect
Aminoglycoside Use with special caution
Risk not known, most manufacturers advice caution
Amoxicillin / Ampicillin Use with special caution
Candidiasis , Diarrhoea
Ciprofloxacin Contraindicated
High concentrations in milk, arthropathy
Clindamycin Contraindicated
Amount in milk small , risk of diarrhoea
Metronidazole Significant amount in milk ,
Avoid
Penicillins Toxicity unlikely but risk of allergy
Sulphonamides Use with special caution
Rashes, small risk of kernicterus, hemolysis in G6PD
deficient
Tetracycline Contraindicated
Growth retardation, candidiasis, tooth discolouration
DRUGS TO BE USED WITH SPECIAL CAUTION / CONTRAINDICATED
IN BREAST FEEDING WOMEN


COMPROMISED RENAL OR HEPATIC FUNCTION

Patients with liver or renal disease may sometimes
need to use antibiotics for unrelated infections and
various surgical and dental procedures.

In order to avoid drug toxicity the prescriber must
be aware of how the drug will be matabolized and
eliminated when selecting a drug or determining
dosage as these are the most common routes of
elimination.

Liver complicated functions and

One of the most important detoxification of drugs
Patients with a pre-existing liver disorder, the
detoxification function compromised
substances that would normally be metabolized could
actually accumulate in the liver or in the bloodstream


Toxic
Beside excretory role in elimination of many antibiotics,
there is intensive metabolism and secretion in kidney,
which is essential for normal functioning of many organs
and systems.


The use of antibiotics in renal failure is associated with
doubled risk of side and toxic effects.


That is the reason why meticulously modificated dosing
of antibiotics eliminating or metabolized by kidney is
essential, particularly antibiotics with small therapic
wideness and antibiotics which cumulate.

Tetracycline family
- When used in larger doses, antibiotics in this family can
cause jaundice, fever, and fatty liver

Erythromycin family
- These antibiotics can cause damage to the liver via
cholestasis (bile retention) and jaundice.
- The harmful effects usually start to show after 10 to 14
days use and the incidence rate is approximately 5 to
10%.
- Clinically, patients may experience stomachache,
nausea, vomiting, jaundice, and elevation of liver
enzymes.


- .



Penicillin family.
- cause the least liver damage and only patients who
are allergic may experience some side effects.
- penicillin family are the most "liver friendly" and
safe for chronic hepatitis patients to use.



GUIDELINES FOR COMPROMISED HEPATIC
FUNCTION
Potential
impairment
Examples of
dental drugs
eliminated
Lab test Range Margin of safety
for dental
prescribing
Hepatic Acetaminophen
Codeine
Diazepam
Erythromycin
Ibuprofen
Ketoconazole
Lidocaine
Lorazepam
Prednisone

AST, ALT, liver
transaminases
30-40 u/l If greater than 4
times normal, do not
use drugs that are
toxic to or
metabolized by the
liver
If available, some laboratory values may serve as guidelines for
prescribing drugs eliminated by the liver
GUIDELINES FOR COMPROMISED RENAL
Potential
impairment
Examples of
dental drugs
eliminated
Lab test Range Margin of safety
for dental
prescribing
Renal Amoxicillin
Cephalosporin
Penicillin
Tetracycline
GFR (Creatinine
Clearance)
<10 ml/min
10-50 ml/min
>50 ml/min
One dose q 24 hrs
One dose q 8-12
hours
One dose q 8 hours

If available, some laboratory values may serve as guidelines for
prescribing drugs eliminated by the kidney
It is important to note most medications prescribed for
dental purposes are prescribed for only a short duration
and many have a large margin of safety, which reduces
the risk of ADRs.

PROPHYLAXIS
For decades, the American Heart Association (AHA)
recommended that patients with certain heart conditions
take antibiotics shortly before dental treatment.

done with the belief prevention of infective
endocarditis (IE)


The AHAs latest guidelines were published in its
scientific journal, Circulation, in April 2007
AHA recommends that most of these patients no longer
need short-term antibiotics as a preventive measure
before their dental treatment.


The guidelines are based on a growing body of scientific
evidence that shows the risks of taking preventive
antibiotics outweigh the benefits for most patients.



Inappropriate use of antibiotics can also lead to the
development of drug resistant bacteria.
no compelling evidence that taking antibiotics prior to a
dental procedure prevents IE in patients who are at risk
of developing a heart infection.

Their hearts are already often exposed to bacteria from
the mouth, which enter their bloodstream during basic
daily activities such as brushing or flossing.

The new guidelines are based on a comprehensive
review of published studies that suggests IE is more
likely to occur as a result of these everyday activities
than from a dental procedure.
The guidelines say patients who have taken prophylactic
antibiotics routinely in the past but no longer need them
include people with:

mitral valve prolapse

rheumatic heart disease

bicuspid valve disease

calcified aortic stenosis

congenital heart conditions such as ventricular septal defect,
atrial septal defect and hypertrophic cardiomyopathy.


The new guidelines are aimed at patients who would
have the greatest danger of a bad outcome if they
developed a heart infection.

Preventive antibiotics prior to a dental procedure are
advised for patients with:
1. artificial heart valves
2. a history of infective endocarditis
3. certain specific, serious congenital (present from birth) heart
conditions, including
unrepaired or incompletely repaired cyanotic congenital heart
disease
a completely repaired congenital heart defect with prosthetic material
or device, during the first six months after the procedure
any repaired congenital heart defect with residual defect at the site
or adjacent to the site of a prosthetic patch or a prosthetic device
4. a cardiac transplant that develops a problem in a heart valve

Frequency, Nature, Magnitude, and Duration of
Bacteremia Associated With a Dental Procedure

Transient bacteremia is common with manipulation of the
teeth and periodontal tissues, and there is a wide variation in
reported frequencies of bacteremia in patients resulting from
dental procedures:
Tooth extraction (10% to 100%),
Periodontal surgery (36% to 88%),
Scaling and root planing (8% to 80%),
Rubber dam matrix/wedge placement (9% to 32%),
Endodontic procedures (up to 20%)
Transient bacteremia also occurs frequently during
routine daily activities unrelated to a dental
procedure, such as

tooth brushing and flossing (20% to 68%),
use of wooden toothpicks (20% to 40%),
use of water irrigation devices (7% to 50%),
chewing food (7% to 51%).


Antibiotics are an important tool in the hands of a
clinician when dealing with infections in
endodontics

It is extremely important to use them appropriately
according to the clinical situation and needs of the
patient

Modification of the drug dosage during specific
medical condition

REFERENCES
Essentails of Medical Pharmacology : KD
TRIPATHI, 5 Edn
Endodontics John I.Ingle 6
th
ed
Pathways of pulp Stephen Cohen
.9
th
ed
Pharmacolgy & Pharmacotherapeutics: RS
SATOSKAR & SD BHANDARKAR, 13 Edn