broad spectrum antibacterial drugs

1. ANTIBIOTICS
BROAD SPECTRUM ANTIBIOTICS
Dr Sanjana Ravindra
1st year PG
Dept. of OMR

2. CONTENT
DEFINITION
INTRODUCTION
HISTORY
PRINCIPLES OF ANTIBACTERIAL THERAPY
CLASSIFICATION AND MECHANISM OF
ACTION
USES OF ANTIBIOTICS
ADVERSE EFFECTS OF ANTIBIOTICS
BROAD SPECTRUM ANTIBIOTIC DRUGS
LOCAL DRUG DELIVERY SYSTEM
ANTIBIOTICS IN DENTISTRY
REFERENCES

3. DEFINITION
S
1) DRUG is any substance or product that is used or intended to be used to modify or explore physiological
systems or pathological states for the benefit of the reciepient
2) PHARMACOKINETICS is the study of absorption, distribution, metabolism and excretion of drugs ie what
the body does to the drug
3) PHARMACODYNAMICS is the study of effects of the drugs on the body and their mechanism of action ie
what the drug does to the body
4) THERAPEUTICS deals with the use of drugs in prevention and treatment of diseases

4. 5) ANTIBIOTIC AGENT Against life (Greek-anti means against and biosis means life). Chemical
substances produced by microorganisms that have the capacity in dilute solutions, to produce antimicrobial
action
6) ANTIMICROBIAL AGENT Substances that will suppress the growth / multiplication of microorganisms.
antimicrobial agents may be antibacterial, antiviral / antifungal
7) ANTIBACTERIAL AGENT substances that destroy or suppress the growth / multiplication of bacteria.
They are classified as antibiotic or synthetic agents
DEFINITION
S

5. INTRODUCTIO
N
Chemical substances produced by
microorganisms that supress the
growth of other microorganisms
and may eventually destroy them.
• K.D. TRIPATHI
Chemical substance produced by
microorganisms, which at a high
dilution can inhibit the growth
and/or multiplication or kill another
microorganism.
• - WAKSMAN AND WOODRUFF(1942)

6. The term 'antibiosis', meaning "against life", was introduced by the
french bacteriologist Jean Paul Vuillemin
 Antibiosis was first described in 1877 in bacteria when Louis Pasteur
and Robert Koch observed that an airborne bacillus could inhibit the
growth of bacillus anthracis
INTRODUCTIO
N
https://www.google.co.in/search?q=antib-hist

7. The term antibiotic was first used in 1942 by Selman
Waksman and his collaborators in journal articles to describe “any
substance produced by a microorganism that is antagonistic to the
growth of other microorganisms in high dilution.”
The term "antibiotic" derives from anti + βιωτικός (biōtikos), "fit for
life, lively“, which comes from βίωσις (biōsis), "way of life“,and that
from βίος (bios), "life“
https://www.google.co.in/search?q=Waksman-antib

8. HISTORY
History of chemotherapy is divided into two phases.
(A) the period of empirical use
(B) modern era.

9. Chinese  ‘mouldy curd’ on boils
Hindus  ‘chaulmoogra oil” in leprosy
Aztecs  ‘chenopodium’ for intestinal worms
Paracelsus  mercury for syphilis and
cinchona bark for fever
PERIOD OF EMPIRICAL USE:
https://www.google.co.in/search?q=plantshist6orical

10.  1871 Joseph Lister experimented with the antibacterial action on human tissue
on what he called penicillium glaucium
 1877 Louis Pasteur postulated that bacteria could kill other bacteria ( anthrax
bacilli)
 1928 Sir Alexander Fleming discovered enzyme lysozyme and the antibiotic
substance penicillin from the fungus Penicillium notatum
 During 1940 and 50s streptomycin, chloramphenicol and tetracyclin were
discovered
 1942 Selman Waksman used the term antibiotics
MODERN HISTORY
https://www.google.co.in/search?q=anti-pioneers

11. https://www.google.co.in/search?q=fleming-alexander

12. BROAD SPECTRUM
1. Tetracycline
2. Chloramphenicol
3. Sulfonamides
4. Trimethoprim
NARROW SPECTRUM
1. Bacitracin
2. Clindamycin
3. Macrolides
4. Metronidazole
5. Penicillin G,V
6. Penicillinase resistant penicillin
7. Polymixin
8. Vancomycin
BASED ON SPECTRUM OF
ACTIVITY
Neidle E A, Pharmacology and therapeutics for Dentistry, 4th edition. Pg 48
EXTENDED
SPECTRUM
1. Aminoglycosides
2. Carbacephems
3. Cephalosporins
4. Extended spectrum of
penicillins
5. Fluoroquinolones
6. Monobactams
CLASSIFICATI
ON

13. BASED ON TYPE OF
ACTION
Bacteriostatic
• Sulfonamides
• Tetracyclines
• Chloramphenicol
• Erythromycin
• Ethambutol
Bactericidal
• Penicillins
• Aminoglycosides
• Rifampin
• Cotrimoxazole
• Cephalosporins
• Vancomycin
• Nalidixic acid
• Ciprofloxacin
Neidle E A, Pharmacology and therapeutics for Dentistry, 4th edition. Pg 48

14. ANTIBIOTICS ARE OBTAINED
FROM
ACTINOMYCETES
Penicillin
Cephalosporin
Griseofulvin
Polymyxin B
Colistin
Bacitracin
Tyrothricin
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Polyenes
BACTERIA
FUNGI
Neidle E A, Pharmacology and therapeutics

15. BASED ON ORGANISMS SUSCEPTIBLE
EFFECTIVE AGAINST GRAM +VE
BACTERIA
PENICILLINS
MACROLIDS
BACITRACIN
EFFECTIVE AGAINST GRAM –VE
BACTERIA
STREPTOMYCIN
EFFECTIVE AGAINST BOTH
GRAM +VE AND –VE BACTERIA
AMPICILLIN
TETRACYCLIN
CHLORAMPHENICOL
AMOXICILLIN
CEPHALOSPORIN
NEOMYCIN
EFFECTIVE AGAINST ACID-FAST
BACILLI
STREPTOMYCIN
RIFAMPIN
KANAMYCIN
AGAINST PROTOZOA
TETRACYCLIN
EFFECTIVE AGAINST FUNGI
NYSTATIN
AMPHOTERICIN B
ANTIMALIGNANCY ANTIBIOTICS
ACTINOMYCIN D
MITOMYCIN

16. PRINICIPLES OF ANTIBIOTIC
THERAPY
Selection of antibacterial agent
Antibacterial combinations
Antibacterial prophylaxis
Microbial drug resistance
Dangers of antibacterial therapy
Misuse of antibacterial agents

17. SELECTION OF ANTIBIOTIC AGENT
1)HOST RELATED FACTORS
Age of the patient
Pregnancy and neonatal period
Immunocompetency status of the patient
Severity of the infection
Allergic reaction and intolerance
Genetic factors
Renal and hepatic function

18. 2)PATHOGEN RELATED FACTORS
Evaluation of the probable microbial etiology and expected clinical course of the
infection
Identification of the causative microorganism and its sensitivity to antibiotic drugs
Possibility of drug resistance
3)DRUG RELATED FACTORS
Nature of the drug
Risk of drug toxicity
The cost of therapy
Pharmacokinetic properties of the drug
Probability of drug compliance by the patient

19. ANTIBACTERIAL
COMBINATIONS
1) SIMULTANEOUS USE OF TWO OR MORE ANTIBIOTICS IS NOT ROUTINELY
RECOMMMENDED. THESE DRUGS CAN BE COMBINED UNDER FOLLOWING REASONS
To achieve an additive or synergistic effect against a single organism
In mixed infections with bacteria sensitive to different drugs
To delay the development of or to overcome the drug resistance
To decrease the adverse reactions to an individual drug
When etiological diagnosis is difficult, the infection is severe and body defense is poor
For reducing chances of superinfections

20. 2) IF A BACTERIOSTATIC DRUG IS COMBINED WITH BACTERIOCIDAL AGENT FOLLOWING
THINGS MAY BE HAPPEN
Drug antagonism
Additive effect oftenly synergestic rarely
3) COMBINED ANTIBIOTIC THERAPY INVOLVES CERTAIN RISKS
Emergence of organism resistant to the multiple drugs used
Increased risk of adverse reactions
Increased risk of superinfection by resistant organisms
Sense of false security
Increase in cost of therapy

21. ANTIBACTERIAL
PROPHYLAXIS
For prevention of meningococcal infections in healthy children during an epidemic,
for prevention of diseases like syphilis, gonorrhea, malaria.
For preventing endocarditis following minor surgical procedures like tonsillectomy
or tooth extraction in patients with cardiac lesions.
For preventing invasion of blood stream by pathogens during certain surgical
manipulations.
In patients with compound musculoskeletal injury, penetrating wounds and skull
injuries.

22. For those puncture wounds that are at high risk of infection.
Animal bite as they are at high risk of infection by oral flora.
To prevent microbial complications like bronchopnemonia e.g. Cases of measles and
tetanus.
In paralytic states to prevent aspiration bronchopnemonia

23. DANGERS OF ANTIBACTERIAL
THERAPY
 Development of allergic and anaphylactic reactions e.g.
Pennicillin
 Selective toxicity
 Development of superinfection
 Development of multiple drug resistant organisms
 Deficiency of certain vitamins
 Fetal damage
 A false sense of security in the patient as well as in physician
 Failure to respond to antibiotic therapy

24. MISUSE OF ANTIBIOTIC
THERAPY
Antibiotic misuse, sometimes called antibiotic abuse or antibiotic overuse.
 Produce serious effects on health.
From antibiotics now available , one needs to know the important representatives of each
class and know them well e.g. Action , dosage .
It is a contributing factor to the creation of multidrug-resistant bacteria, informally called
"super bugs" relatively harmless bacteria can develop resistance to multiple antibiotics and
cause life-threatening infections.

25. MICROBIAL DRUG RESISTANCE
The recent emergence of antibiotic resistance in bacterial pathogens, both nosocomialy and in
the community, is a very serious development that threatens the end of the antibiotic era.
Drug resistance is not a characteristic of all bacteria and many strains responsible for common
infections have largely remained susceptible to antibiotics e.G. Pneumococci, streptococcus
pyogenes, meningococci, and treponema pallidum.

26. Bacterial resistance is often quantitative and not qualitative. Thus an antibacterial substance which
is not effective in small doses may inhibit the bacteria in vitro in large concentrations.
For an antibiotic to be effective, it must reach its target in an active form, bind to the target, and
interfere with its function.
Accordingly, bacterial resistance to an antimicrobial agent is attributable to three general
mechanisms:
(1) the drug does not reach its target,
(2) the drug is not active, or
(3) the target is altered .

27. Natural resistance
In organisms which are naturally resistant, the drug sensitive enzyme reactions may be absent .
 some naturally resistant organisms may elaborate a substance which destroys the antibiotic e.G.
E coli produce pencillinase which destroys penicillin .
Following the use of an antibiotic agent which destroys the sensitive strain , these naturally
resistant variants multiply and become dominant.

28. Some microbes have always been resistant to certain antibacterial agents.
They lack the metabolic process or the target site which is affected by the particular drug.
This is generally a group or species charateristic e .G. Gm-ive bacilli are normally unaffected by
penicillin G or M. Tuberculosis is insensitive to tetracyclines.

29. Acquired microbial 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 can happen with any microbe and is a major clinical problem.
However, development of resistance is dependent on the microorganism as well as the drug.
Some bacteria are notorious for rapid acquisition of resistance, e.G. Staphylococci, coliforms, tubercle
bacilli.
.

30. Others like strep. Pyogenes and spirochetes have not developed significant resistance to penicillin
despite its
Widespread use for > 50 years.
It can arise in bacteria in several ways. Microbes acquire resistance after a change in their DNA. Such
change may occur in
A) genetic mutation
B) genetic exchange - conjugation
- Transduction
- Transformation

31. Mutation
It is a stable and heritable genetic change that occurs spontaneously and randomly among
microorganisms.
 Any sensitive population of a microbe contains a few mutant cells which require higher
concentration of the ama for inhibition.
Mutation and resistance may be:
(I ) single step.- A single gene mutation may confer higher degree of resistance; emerges rapidly,
e.G. Enterococci to streptomycin, E. Coli and staphylococci to rifampin
(Ii ) multistep.· A number of gene modifications are involved, sensitivity decreases gradually in a
stepwise manner. Resistance to erythromycin, tetracyclines and chloramphenicol is developed by
many organisms in this manner.

32. Conjugation : This may involve chromosomal or extrachromosomal (plasmid) dna.
 The gene carrying the 'resistance' or 'r' factor is transferred only if another 'resistance transfer
factor' (rtf) is also present.
Chloramphenicol resistance of typhoid bacilli, streptomycin resistance of e. Coli, penicillin
resistance of haemophilus.
Concomitant acquisition of multidrug resistance has occurred by conjugation. Thus, this is a very
important mechanism of horizontal transmission of resistance.
GENE TRANSFER

33. TRANSDUCTION:
It is the transfer of gene carrying resistance through the agency of a
bacteriophage.
The r factor is taken up by the phage and delivered to another bacterium which it
infects.
Certain instances of penicillin, erythromycin and chloramphenicol resistance
have been found to be phage mediated.

34. TRANSFORMATION :
 A resistant bacterium may release the resistance carrying DNA into the medium and this may be
imbibed by another sensitive organism-becoming unresponsive to the drug.
 This mechanism is probably not clinically significant except isolated instances of pneumococcal
resistance to penicillin g due to altered penicillin binding protein

35. CROSS RESISTANCE :
Acquisition of resistance to one AMA conferring resistance to another AMA, to which the organism
has not been exposed, is called cross resistance.
This is more commonly seen between chemically or mechanistically related drugs, e.G. Resistance
to one sulfonamide means resistance to all others, and resistance to one tetracycline means
insensitivity to all others.
Sometimes unrelated drugs show partial cross resistance, e.G. Between tetracyclines and
chloramphenicol, between erythromycin and lincomycin.

36. PREVENTION OF DRUG RESISTANCE
No indiscriminate and inadequate or unduly prolonged use of amas should be made. This would
minimize the selection pressure and resistant strains will get less chance to preferentially propagate.
Prefer rapidly acting and selective (narrow spectrum) amas whenever possible; broad-spectrum
drugs should be used only specifically.
Use combination of amas whenever prolonged therapy is undertaken, e.G. Tuberculosis, SABE.
Infection by organisms notorious for developing
Resistance, e.G. Staph. Aureus, E. Coli, M. Tuberculosis,
Proteus, etc. Must be treated intensively.

38. INDICATIONS OF ANTIBIOTICS
* Diabetics mellitus,
immunoglobulin deficiency,
malnutrition and alcoholism.
* Acute severe rapidly
spreading infection
* Pericoronitis,
osteomyelitis, fracture, soft
tissue wound and
odontogenic infection
* Post operative wound
infection
* Prevention of endocarditis
in high risk patients
undergoing any dental
procedures that is likely to
cause gingival bleeding
THERAPEUTIC
PROPHYLACTIC

39. USES OF
ANTIBIOTICS
Infections of all systems
 Pus formation
Sepsis
Quinsy
Skin infections
Mucous membrane infections
Septicaemia
Empirical therapy
Prophylactic therapy

40. CONTROL AND ERADICATION OF INFECTIONS OF ORAL CAVITY.
• Local factors;
1) Swelling,
2) Lymphadenitis,
3) Trismus,
4) Dyshagia
5) Chronic draining sinus tract.
• Systemic factors;
1) Cellulitis.
2) Osteomyelitis.
3) Infections of salivary gland.
4) Compound fractures.
5) Infected cysts.
6) Infected oro-antral fistula.
7) Pericoronitis

41. SIDE EFFECTS OF
ANTIBIOTICS
Diarrhoea
Bloating and indigestion
Abdominal pain
Loss of appetite
Being sick
Feeling sick
Itchy skin rash
Coughing
Life-threatening allergic reaction

42. BROAD SPECTRUM
ANTIBIOTICS
1. TETRACYCLINE
2. CHLORAMPHENICOL
3. SULFONAMIDES
4. TRIMETHOPRIM

43. TETRACYCLIN
E
Defination : They are octahydro napthacene derivatives which are bacteriostatic and broad
spectrum antibiotics that kills certain infection causing microorganisms and are used to treat wide
variety of infections.
 Tetracyclines are napthacene derivatives.
 The napthacene nucleus is made up by fusion of 4 partially unsaturated
cyclohexane radicals and hence the name tetracyclines.
 Tetracyclines are bacteriostatic & effective against rapidly multiplying
bacteria
https://www.google.co.in/search?q=tetracycline+structure

44. According to duration of action:
• Short-acting (Half-life is 6-8 hrs)
• Tetracycline
• Chlortetracycline
• Oxytetracycline
• Intermediate-acting (Half-life is ~12 hrs)
• Demeclocycline
• Methacycline
• Long-acting (Half-life is 16 hrs or more)
• Doxycycline
• Minocycline
• Tigecycline
CLASSIFICATI
ON

45.  Primarily bacteriostatic.
 Inhibit protein synthesis by binding to 30s ribosomes in susceptible organism. Thus, attachment of
aminoacyl-t-rna to the mrna-ribosome complex is interfered with. As a result, peptide chains fail to
grow.
 It is effective against gram –ve and gram +ve bacteria, rickettsial, spirochetees, protozoa and
mycoplasma.
MECHANISM OF ACTION
tripathi

46.  Orally- saliva- liver- bile
 They cross placental barrier
 Tetracyclines have chelating property-form insoluble & unabsorbable complexes with
calcium and other metals.
 Doxycycline & minocycline are completely absorbed irrespective of food.
 Milk, iron preparations, nonsystemic antacids & sucralfate reduce their absorption .
administration of these substances & tetracyclines should be staggered, if the cannot be
avoided altogether.
PHARMACOKINETICS

47. (A) IRRITATIVE EFFECTS:
- Epigastric pain, nausea, vomiting, diarrhoea.
- Doxycycline is known to cause esophageal
ulcerations.
(B) DOSE RELATED TOXICITY:
1.) LIVER DAMAGE:
- Fatty infiltration of liver, jaundice, in pregnancy,
Can cause acute hepatic necrosis.
ADVERSE EFFECTS

48. 2.) KIDNEY DAMAGE:
- Fancony syndrome – like condition
3.) PHOTOTOXICITY:
- Sunburn, severe skin reactions
4.) ANTIANABOLIC EFFECT :
- Reduce protein synthesis & have an overall catabolic
effect.
- They induce negative nitrogen balance & can increase blood urea.

49. 5.) LNCREASED INTRACRANIAL PRESSURE In some infants.
6.) DIABETES INSIPIDUS
- Demeclocycline antagonizes ADH action & reduces urine concentrating
ability of the kidney.
7.) VESTIBULAR TOXICITY
- Minocycline has produced vertigo which subside when the drug is
discontinued.

50. (C) HYPERSENSITIVITY
- This is infrequent with tetracyclines.
- Skin rashes, urticaria, glossitis, pruritus, even
exfoliative dermatitis have been reported.
- Angioedema & anaphylaxis are extremely rare.
(D) SUPERINFECTION:
- Marked suppression of the resident flora.
- Intestinal superinfection by candida albicans can occur.
- Oral manifestations are very rare.

51. https://www.google.co.in/search?q=tetracycline+staining
 Hypoplasia and brown discolouration of teeth
 Not used in 3rd trimester
 Deposits in bones and teeth- yellow discolouration
 Not recoomended- children below 8 yrs and
pregnant women – permanently discolour
developing teeth and alter bone growth
(E) TOOTH DISCOLOURATION

52. PRECAUTIONS
1.) Tetracyclines should not be used during pregnancy, lactation and in
children.
2.) They shouldbe avoided in patients on diuretics: blood urea may rise in such
patients.
3.) They should be used cautiously in renal or hepatic insufficiency.
4.) Preparations should never be used beyond their expiry date.
5.) Do not mix injectable tetracyclines with penicillin-inactivation occurs.
6.) Do not inject tetracyclines intrathecally.

53. (A) MEDICINAL USES
- Clinical use has declined due to the introduction of Fluoroquinolones and other
agents.
- DRUG OF 1ST CHOICE:
(A) venereal diseases
(B) atypical pneumonia
(C) cholera  limit the diarrhoea duration.
(D) brucellosis  combined with gentamicin.
(E) plague
(F) relapsing fever.
(G) rickettsial infections.
USES

54. - DRUG OF 2ND CHOICE:
(A) to penicillin / ampicillin for tetanus , anthrax , actinomycosis infections.
(B) to ciprofloxacin / ceftriazone for gonorrhea in patients allergic to
penicillin.
(C) to ceftriaxone for syphilis in patients allergic to penicillin.
(D) to azithromycin for chlamydial infections.
- Also can be used for UTI , pneumonia, amoebiasis, acne, lung disease.

55. (B) dental uses :
• of limited use in treating acute infections , but are of importance in
periodontal disease.
• Suppress the activity of collagenases derived from the neutrophils and
fibroblasts, that contribute to gingival inflammation.
• Collagenases are calcium dependent & tetracyclines chelate the calcium.
• May benefit periodontal inflammation by releasing free radicals of
oxygen.

56. ADMINISTRATION
 oral capsule is the dosage form in which tetracyclines are most commonly
administered.
 The capsule should be taken 1/2 hr before or 2 hr after food.
 Not recommended by i.M. Route because it is painful & absorption from the
injection site is poor.
 Slow i.V. Injection may be given in severe cases, but is rarely require now.
 A variety of topical preparations are available , but should not be use
because there is high risk of sensitization .

57. OXYTETRACYCLINE:
(TERRAMYCIN)
250 – 500 MG EVERY 6 HRS
TETRACYCLINE:
(ACHROMYCIN, RESTECLIN)
250 MG – 4 G EVERY 6 HRS
DOSAGES
https://www.google.co.in/search?q=tetracycline+tablet

58. DEMECLOCYCLINE:
(LEDERMYCIN)
ADULT: 150 MG 4 X DAILY
300 MG BID.
CHILD: 7 – 13 MG/KG DIVIDED
EVERY 6 – 12 HRS.
MINOCYCLINE:
(CYANOMYCIN)
ADULT: 200 MG
FOLLOWED
BY 100 MG EVERY 12
HRS.
CHILD: 4 MG/KGhttps://www.google.co.in/search?q=tetracycline+tablet

59. DOXYCYCLINE:
(TETRADOX, BIODOXI, DOXT, NOVADOX)
ADULT: 200 MG ON DAY 1 FOLLOWED BY 100 MG OD
CHILD: 4 MG/KG IN 2 DIVIDED DOSES, FOLLOWED BY 2
MG/KG DAILY.
https://www.google.co.in/search?q=tetracycline+tablet

60. TETRACYCLINE EFFECTIVE IN TREATING PERIODONTAL DISEASE
BECAUSE
• Adjuvant role in Chronic Periodontitis - control gingival inflammation -
normalize the periodontal microflora from a mixture of anerobic G- bacilli and
spirochetes.
• Highly active against Actinobacillus actinomycetum comitans in
Aggressive Periodontitis - prevents gingival destruction and bone loss.

61. TERATOGENIC EFFECTS OF
TETRACYCLINES
PERIOD STRUCTURE AFFECTED DEFORMITY
mid pregnancy to 5 months of
postnatal life
Deciduous teeth Brownish discolouration, ill
formed and are more
susceptible to caries
2 months to 5 years of age Permanent teeth Pigmentation, discolouration
Pregnancy and childhood up to
8 years of age
Skeleton Depressed bone growth

63. CHLORAMPHENICO
L
• Broad spectrum antibiotic first obtained from streptomyces venezuelae.
MECHANISM OF ACTION
 It is bacteriostatic but for some organisms it is bacteriocidal. It binds to 50s ribosomal subunit and inhibits
protein synthesis
 It is unique among natural compounds because it contains a NITROBENZENE moiety and is a derivative of
DICHLOROCETIC ACID.
 It acts by inhibiting protein synthesis (by binding reversibly to the 50s ribosomal subunit).
https://www.google.co.in/search?q=chloramphenicol+structure

64. 64
USES :
 Typhoid fever(S.typhi)
 Bacterial meningitis (H.influenzae)
 Anaerobic infections
 Rickettsial disease (eg.Rocky mountain spotted fever)
 Brucellosis
 UTI
Adult 250 -500mg 6hrly
Children 25 – 50mg /kg/day

65. 65
ADVERSE EFFECTS :
 Bone marrow depression
 Hypersensitivity reactions
 Irritative effects
 Superinfections
 Gray baby syndrome

66. GRAY BABY SYNDROME / ASHEN GRAY
CYANOSIS
Newborn babies given high doses of chloramphenicol –
develop vomiting, refusal of feeds, hypotonia,
hypothermia, abdominal distension, metabolic acidosis
https://www.google.co.in/search?q=gray+baby

67. It is the fixed dose combination of trimethoprim and sulfamethoxazole.
Trimethoprim it is diaminopyrimidine and related to
antimalarial drug pyrimethamine.
 Sulfamethoxazole
selected for the
combination
because it has
nearly the same
T ½ as trimethoprim.
COTRIMOXAZOL
E

68. ANTIBACTERIAL SPECTRUM :
Individually, both sulfonamide and trimethoprim are bacteriostatic.
Combination becomes cidal against many organisms.
Organisms covered by the combination are-salmonella typhi,
serratia, klebsiella, enterobacter, pneumocystis jiroveci.
 Many sulfonamide resistant strains of staph. Aureus, strep.
Pyogenes, shigella, enteropathogenic E. Coli, influenzae ,
gonococci and meningococci.

69. Why sulfamethoxazole + trimethoprim ?
Both have nearly the same t1/2 (- 10 hr).
Optimal synergy is exhibited at a concentration ratio of Sulfamethoxazole 20 :
trimethoprim 1.
MIC of each component may be reduced by 3-6 times.
This ratio is obtained in the plasma when the two are given in a dose ratio of 5 : 1,
because trimethoprim enters many tissues, has a larger volume of distribution than
sulfamethoxazole and attains lower plasma concentration

70. PHARMOKINETICS :
Trimethoprim crosses blood-brain barrier and placenta, while sulfamethoxazole
has a poorer entry.
Trimethoprim is more rapidly absorbed than sulfamethoxazole.
 Trimethoprim is 40% plasma protein bound, while sulfamethoxazole is 65%
bound.
Trimethoprim is partly metabolized in liver and excreted in urine.

71. ADVERSE EFFECTS:
 Nausea, vomiting, stomatitis, headache, rashes.
 Rarely, folate deficiency (megaloblastic anemia)
 Blood dyscrasias.

72. CONTRAINDICATIONS:
 Pregnancy: - teratogenic effects may occur due to trimethoprim.
- Neonatal haemolysis, methaemoglobinaemia.
 Renal disease: - patient may develop uraemia.
 Aids patients: - fever, rash, bone marrow hypoplasia.
 Elderly patients: - bone marrow toxicity.
 Diuretics + cotrimoxazole = thrombocytopenia.

73. USES:
 Tonsilitis, pharyngitis, sinusitis, otitis media, chronic bronchitis.
 Orodental uses very rare  only if allergies to β – lactam antibiotics are present.
 Major indications include uti, bacterial dysentery.
 Effective alternative to chloramphenicol in the case of typhoid fever, but strains
are known to be resistant.
 Alternative for chancroid, granuloma inguanale, neutropenic patients.
BRAND NAME
SEPTRAN, SEPMAX,
BACTRIM, CIPLIN,
ORIPRIM, SUPRISTOL,
FORTRIM.

74.  First anti-microbial agents effective against pyogenic bacterial infections.
Sulfonamido-chrysoidine (prontosil red)  used by Domagk to treat streptococcal
infection in mice.
SULPHONAMID
E

75. A LARGE NUMBER OF SULFONAMIDES WERE PRODUCED AND
USED EXTENSIVELY,
BUT BECAUSE OF RAPID EMERGENCE OF BACTERIAL RESISTANCE
AND AVAILABILITY OF MANY SAFER AND MORE EFFECTIVE
ANTIBIOTICS
CURRENT UTILITY IS LIMITED
EXCEPT IN COMBINATION WITH TRIMETHOPRIM
(COTRIMAXOZOLE) AND PYRIMETHAMINE.

76. CLASSIFICATION:
(A) short acting (4-8 hrs):
- Sulfadiazine.
(B) intermediate acting (8-12 hrs):
- sulfamethoxazole, sulfamoxole.
(C) long acting (approx. 7 days):
- Sulfadoxine, sulfamethopyrazine.
(D) special purpose sulfonamides:
- Sulfacetamide sodium, sulfasalazine mafenide, silver
sulfadiazine.

77. ANTIBACTERIAL SPECTRUM :
They are primarily bacteristatic against gm +ve and gm –ive bacteria.
However , bacteriocidal action can be attained in urine.
Sensitive to strepto. Pyogenes , haemophilus influenzae , vibrio cholerae ,
meningococci , gonococci , E coli and shigella.

78. RESISTANCE:
Some bacteria are capable of developing resistance to sulfonamides like
pneumococci, gonococci, staph. Aureus, meningococci, some strep. Pyogenes.
It is due to
(a) produce increased amounts of PABA.
(B) folate synthetase enzyme has low affinity.
(C) adopt an alternative pathway for folate
metabolism.

79. Pharmacokinetics:
Rapidly absorbed by the g.I.T.
Extent of plasma binding differs in different members ( 10 – 90 % ).
Highly protein bound members are longer acting .
 attains the same concentration in the csf as in plasma.
 Excreted mainly by the kidney through glomerular filtration.
The more lipid soluble members are highly reabsorbed in the tubule hence longer
acting .
Crosses placenta freely.

80. THE PRIMARY PATHWAY FOR THE METABOLISM OF
SULFONAMIDES IS
ACETYLATION AT N 4 BY NON MICROSOMAL ENZYME IN
LIVER
THE ACETYLATED DERIVATIVE IS INACTIVE
AND GENERALLY LESS SOLUBLE IN URINE THAN PARENT
DRUG
MAY PRECIPITATE

81. Sulfadiazine :
Rapidly absorbed orally
Rapidly excreted in urine
 50% plasma protein bound
20-40% acetylated
Aderivative is less soluble in urine = crystalluria
Good penetrabilityi n brain and CSF
Preferred compound for meningitis
Dose: 0 5 g qid to 2 g tds; sulfadiazine 0.5 g tab

82. Sulfamethoxazole :
Slower oral absorption
Slower urinary excretion
 T 1/2 in adults is 10 hours
Preferred compound for combining with trimethoprim because the
t1/2 of both is similar
A high fraction is acetylated – crystalluria
dose: 1 g BD for 2 days, then 0.5 g BD.
Gantanol 0.5 g tab.

83. Sliver sulfadiazine :
Active against a large number of bacteria and fungi,
It slowly releases silver ions which appear to be largely responsible for the
antimicrobial action
Most effective drugs for preventing infection of burnt surfaces and chronic
ulcers and is well tolerated.
It is not good for treating established infection.
Local side effects are-burning sensation on application and itch.
Sil vlrin 1% cream,
argenex 1% cream
With chlorhexidine 0.2%.

84. ADVERSE EFFECTS :
 Crystalluria is dose related
Hypersensitivity reactions occur in 2-5 % patients. These are mostly in
the form of rashes, urticaria and drug fever.
Photosensitization is reported.
Stevens-johnson syndrome and exfoliative dermatitis are more common
with long-acting agents.
Hepatitis, unrelated to dose, occurs in 0.1 % patients.•

85. Topical use of sulfonamides is not recommended because of risk of contact
sensitization.
• Sulfonamides cause haemolysis in a dose dependent manner in individuals
with g-6-pd deficiency.
Neutropenia and other blood dyscrasias are rare.
• Kernicterus may be precipitated in the newborn, especially premature, by
displacement of bilirubin from plasma protein binding sites and more permeable
blood-brain barrier

86. Interactions :
 sulfonamides inhibit the metabolism (possibly displace from protein binding
also ) of phenytoin, tolbutamide and warfarin enhance their action.
They displace methotrexate from binding and decrease its renal excretion =
toxicity can occur.
Fixed dose combinations of sulfonamides with penicillins are banned in india.

87. Uses :
Systemic use of sulfonamides alone is rare now.
Though they can be employed for suppressive therapy of chronic uti, for
streptococcal pharyngitis and gum infection.
Combined with trimethoprim (as cotrimoxazole) sulfamethoxazole is
used for many bacterial infections and nocardiasis .

88. Along with pyrimethamine, certain sulfonamides are used for malaria and
toxoplasmosis.
Ocular sulfacetamide sod. (10-30%) is a cheap alternative in trachoma/
inclusion conjunctivitis.
Topical silver sulfadiazine or mafenide are used for preventing infection on
burn surfaces.

89. 89
LOCAL DRUG DELIVERY OF
ANTIBIOTICS
• Limitation of systemic therapy, mouth rinse & irrigation have, promoted for
research for development of alternative delivery system
• Requirement of treating periodontal disease include
1. Controlled release of drug
2. Maintained localized concentration of drug at infection site for optimum
time
3. Minimal side effect

90. 90
VARIOUS LOCAL DRUG DELIVEREY OF
ANTIBIOTICS
• ACTISITE (TETRACYCLINES)
• ARESTIN (MINOCYCLINE)
• ATRIDIOX (METRONIDAZOLE )
• PERIO CHIP (CHLOR HEXIDINE)
• ELYZOL (METRONIDAZOLE )

91. 91
TETRACYCLINE – CONTAINING
FIBER (ACTISITE )
First local delivery product for antibiotic Feature
1. Ethylene or vinyl acetate copolymer fiber
2. Diameter 0.5 mm
3. Containing Tetracycline 12.7 mg/ 9 inch
4. When packed into periodontal pocket, it is well tolerated by oral tissue
5. For 10 day it sustains tetracycline concentration exceeding 1300 ug/ ml
https://www.google.co.in/search?q=LDD+actisite

92. 92
ACTISITE.......
Effect
Reduction in probing depth
Reduction in Bleeding on probing
Increase in clinical attachment level
Normally no staining on teeth
Reduction in plaque micro organism

93. 93
SUB GINGIVAL DELIVERY OF
DOXYCLINE ATRIDIOX
• Atridox is gel system that incorporate the antibiotic Doxycycline (10%) in syringeable gel
system
• It is a Biodegradable mixture
• Drug introduced Subgingivally
• Applied with or without Scaling or Root planning
Effect
Increase in clinical attachment level
Reduction in plaque micro organism
Probing depth reduction
https://www.google.co.in/search?q=LDD+ATRIDIOX

94. 94
SUB GINGIVAL DELIVERY FOR
MINOCYCLINE (ARESTIN)
1. Sub Gingival Delivery system contain 2% (w/w) Minocycline hydrochloride
2. Use as a adjuvant to Sub Gingival debridement
3. Biodegradable mixture in syringe
Effect are
Reduction in Pocket depth
Reduction in gingival bleeding
Reduction in plaque microorganism

95. 95
SUB GINGIVAL DELIVERY OF
METRONIDAZOLE ELYZOL
• ELYZOL Containing an oil based Metronidazole 25% dental gel
• Applied in viscous consistency to the pocket where is liquidized by body heat and
hard again contact with water
• Preparation contain Metronidazole benzoate, which is converted into active
substance by
esterase in GCF
• Effective after scaling & Root planning

96. ANTIBIOTIC PROPHYLAXIS FOR DENTAL
PROCEDURES
 Definition:
“The administration of antibiotics to patients who have no known infection in order to prevent
microbial colonization and reduce the potential of post – operative complications.”
- Michael g. Newman
 Principles:
(A) benefits > risks.
(B) antibiotic loading dose should be used
(C) should be selected based on the most likely organism to cause an infection.
(D) should be present in the blood and target tissues before the spread of micro –
organisms.
(E) should be continued as long as contamination persists

97.  American Heart Association: (Infective Endocarditis)
SITUATION DRUG
DOSAGE (30 – 60 min. before
procedure single dose)
Oral Administration Amoxicillin
Adults: 2 g
Children: 50 mg/kg
Inability to take Oral medication
a.) Ampicillin
b.) Cefazolin/Ceftriaxone
Adults: 2 g I.M/I.V.
Children: 50 mg/kg I.M/I.V
Adults: 1 g I.M/I.V
Children: 50 mg/kg I.M/I.V
Allergy to Penicillin and
Ampicillin
a.) Clindamycin
b.) Azithromycin/Clarithromycin
c.) Cephalexin
Adults: 600 mg
Children: 20 mg/kg
Adults: 500 mg
Children: 15 mg/kg
Adults: 2 g
Children: 50 mg/kg
Allergy to Penicillin and
Ampicillin + Inability to take oral
medication
a.) Cefazolin/Ceftriaxone
b.) Clindamycin Phosphate
Adults: 1 g I.M./I.V.
Children: 50 mg/kg I.M./I.V.
Adults: 600 mg I.M/I.V
Children: 20 mg/kg I.M/I.V.

98. ANTIBIOTICS IN VARIOUS DENTAL
CONDITIONS
WHEN ARE ANTIBIOTICS USED?
 Useful as treatment adjuncts to conventional periodontal therapy.
 Successful when the micro-organism has reached the connective tissue of the diseased
gingiva.
 They should never be used if treatment is removal of plaque. Agent is most effective when the
dominant micro – organism is determined.

99. CONDITION DRUG DOSAGE
Acute Ulcerative Necrotizing
Gingivitis
a) Amoxicillin
b) Metronidazole
a.) 500 mg QID x 5 days
b.) 400 mg TID x 7 days.
Periodontal Abscess
a) Amoxicillin
b.) Clindamycin ( Penicillin
allergy)
c.) Azithromycin
a.) 1 g loading dose, then 500
mg TID x 3 days
b.) 600 mg loading dose, then
300 mg QID x 3 days.
c.) 1 g loading dose, then 500
mg QID x 3 days.
Localized Aggressive
Periodontitis
a.) Tetracycline
b.) Doxycycline
c.) Augmentin ( If resistant to
the Tetracyclines)
a.) 250 mg x 14 days, every 8
weeks.
b.) 100 mg/day
c.) 325 mg TID x 14 days.

100. Endodontic Infections:
- Acute Periapical Abcess:
Amoxicillin 500 mg TID x 5 days
- Adjunctive Treatment:
Penicillin 1 g loading dose, then 500 mg every 6 hrs x 7 – 10 days.
Penicillin Allergy:
Erythromycin 1 g loading dose, then 500 mg every 6 hrs x 7
days.
Doxycycline 200 mg loading dose, the 100 mg every 6 hrs x 7
days.

101.  Cellulitis:
Adult: Amoxicillin 500 mg TID x 5 days
Child: 20 – 50 mg/kg/day in 2 – 3 divided doses.
 Osteomyelitis:
1.) Aqueous Penicillin 2 MU I.V. every 4 hrs +
Metronidazole 400 mg every 6 hrs.
If condition improves after 48 – 72 hrs, then switch to
Penicillin V 500 mg every 4 hrs + Metronidazole 400 mg every 6
hrs x 4 – 6 weeks.
2.) Ampicillin 1.5 -3 g x 6hrs.
If condition improves after 48-72hrs
switch to Augmentin 1 g BID x 4 – 6 weeks

102. 3.) Penicillin V 2g + Metronidazole 400 mg every 8 hrs. x 2 -
4weeks after last the seqestrum was removed and the patient was
without symptoms
4.) Clindamycin 600 - 900mg every 6 hrs. I.V. then Clindamycin 400
- 600mg every 6 hours or 2-4 weeks
5.) Cefoxitin 1 g every 8 hours I.V. / 2 g every 4 hrs I.M. until no
symptoms, then switch to Cephalexin 500 mg every 6 hrs for 2-6
weeks.

103.  Dento – Alveolar Abscesses/Space Infections:
- Amoxicillin 500 mg TID x 5 days.
Metronidazole 400 mg TID x 5 days.
- Penicillin Allergy: Clindamycin 600 mg
 Pediatric Doses:
(a) Amoxicillin: 250 mg TID x 5 days.
20 – 40 mg/kg oral susp.
(b) Ampicillin: 50 – 100 mg/kg in 4 divided doses
(c) Cephalexin: 25 – 50 mg/kg in 4 – 6 divided doses.
(d) Clindamycin: 8 – 25 mg/kg in 3 – 4 divided doses.
(e) Erythromycin: 30 – 40 mg/kg in 4 divided doses
(f) Penicillin V: 25 – 50 mg/kg in 4 divided doses.

104. CULTURE SENSITIVITY AND
TESTING
 Many oral infections are treated without identification of the specific etiologic agent.
 This leads to unsuspected resistance and therefore the treatment can become
unsuccessful or inadequate.
 Quantitative Tests:
- Determines how much the minimum inhibitory concentration inhibits the growth of
the organism.

105. - Minimum Inhibitory Concentration: (MIC)
- Lowest concentration of the agent that inhibits the growth of the organism.
- Minimum Bactericidal Concentration: (MBC)
- Lowest concentration of antimicrobial agent that allows less that 0.1 % of the
original inoculum to survive.
 METHODS OF SUSCEPTIBILITY TESTING:
(a) Chromogenic Cephalosporin Test:
- Used to detect the β – Lactamase enzyme.
- Colour of the disc changes from yellow to red.

106. (b) Disc Diffusion Method:
- Incorporates the measurement of zone diameters,
representing the ability of a particular agent to exert its effect.

107. (c) Dilution Methods:
- Recommended for slow growing facultative anaerobic
bacteria found in oral infections.
- Also determines the bactericidal activity of synergism or
antagonism between agents.
(e.g Microdilution test, Agar dilution test)
 Interpretation of Results:
- An organism is considered to be susceptible if the Minimal
Inhibitory Concentration is lower than the peak concentration in
blood.

108. LIST OF
REFERENCES
1. www.Merriam-webster.Com
2. Essentials of general pharmacology, K D Tripati : Jaypee Publications,5th edition 2003
3. Goodman and Gilman. The pharmacological basis of therapeutics, 9th edition.
4. Michael G Newman, “Antibiotic/Antimicrobial Use in Dental Practice”
5. CIMS India (www.mims.com)
6. Dental pulse for entrance examination
7. Maureen K Bolon, “The Newer Fluoroquinolones,” 2011
8. www.medical.theclinics.com

109. 9. Foundation in microbiology: basic principle by Kathleen park, 2nd edition
10.Lippincott’s illustrated reviews pharnacology., 2nd edition 2000
11.Satoskar, bhandarkar , Nirmala rege . pharmacology and therapeutics, 20th edition.
12.Burket's textbook of oral medicine, lester william burket, martin s. Greenberg, michael glick, jonathan
A. Ship 11th edition,
13.Carranza's clinical periodontology, michael G. Newman, henry takei, perry R. Klokkevold, fermin A.
Carranza
LIST OF
REFERENCES