#surgery #seminar

1. Antibiotics
By,
ASWANTH.E.P

2. Contents
Introduction
Classification of AMAs
Factors affecting choice
of AMAs
Combined use of antibiotics
Drug resistance
Beta lactam aantibiotics
a)Penicillins
b)Cephalosporins
Tetracyclines
Sulfonamides
a)Cotrimoxazole
b)Quinolones
Macrolides
Aminoglycosides
Antibiotic prophylaxis
Conclusion
Reference

3. INTRODUCTION
Antibiotics are substances produced by
microorganisms which are selectively supress the
growth or kill other microorganisms at low
concentrations.
Chemotherapy is the treatment of systemic infections
with specific drugs that selectively supress the infecting
microorganism without significanly affecting the host.
Appropriate choice of drugs are important in any
treatment and its prognosis.

4. Classification
1)Based on mechanism of action
a)Inhibit cell wall synthesis : Penicillins,cephalosporins
b)Inhibit protein synthesis : Tetracyclins,Chloramphynicol
c)Inhibit DNA gyrase : Fluoroquinolones
d)Interfere DNA synthesis : Acyclovir
e)Causing misreading of mRNA &
affect permiability : Aminoglycosides
2)Based on spectrum of activity
a)Narrow Spectrum : Penicillin G,Streptomycin
b)Broad spectrum : Tetracyclins,Chloramphinicol

5. 3)Based on type of action
a)Primarily bacteriostatic : Tetracyclines,Chloramphinicol
b)Primarily bacteriocidal : Penicillins,Cephalosporins
4)Based on type of organisms against which
primarily active
a)Antibacterials: Penicillins,Aminoglycocides
b)Antifungal : Ketoconazole,Amphotericin B
c)Antiviral : Acyclovir,Zidovudine

6. Factors affecting choice of AMA’s
1)Patient factors :
Age
Renal & hepatic function
Local factors like :
a)Presence of pus & secretions
b)Presence of necrotic material/foreign body
c)pH
Drug allergy
Impaired host defence

7. Pregnancy
All AMAs should be avoided due to risk of foetus.
Penicillins,cephalosporins &erythromycin are safe.
Tetracycline contraindicated-Pancreatitis & kidney damage
in mother and teeth & bone deformities in children.
Aminoglycosides causes foetal ear damage.
Genetic factors
Sulfonamides,fluoroquinolones carry risk of producing
haemolysis in G6PD deficient patient.

8. 2)Drug factors
Spectrum of activity
For definitive treatment – Narrow spectrum & for
emperical – broad spectrum
Type of activity
Acute infection resolve faster with cidal than with
static,as the cidal drug reduces the number of bacteria at
the site of infection while static only prevent the increase
in the number.
Sensitivity of organism
Relative toxicity-less toxic preferred(i.e beta lactam over
aminoglycosides)

9. Route of administration
Penicillin G have to be given by injection (20-24MU
daily)
For less severe infections, oral antibiotic is
preferrable.But for serious infection like meningitis
parenteral would be more reliable.
Cost

10. Combined use of antibiotics :
1)To achieve synergism :
Synergism(supra additive effect),additive action,
antagonism may be observed when 2 AMAs used together.
If MIC of one AMA is reduced in presence
of other– Synergism

11. 2)To reduce severity / incidence of adverse effects
Needed for AMAs with low safety margin
Amphotericin B + rifampin : the latter is not themselves
antifungal but enhance action of amphotericin B.
3)To prevent emergence of resistance
4)To broaden the spectrum of antibiotic
a)Treatment of mixed infection
b)Initial treatment of severe infections

12. Disadvantages :
Toxicity of one agent may enhanced by another.
Increased chances of super infections
High cost of therapy
Emergence of resistance

13. Drug Resistance
1)Natural resistance :
Develop due to lack of metabolic processes or the
target site which is affected by the particular drug.
Eg : gram negative bacilli are unaffected by penicillin G
2)Acquired resistance :
Arise due to use of an AMA over a period of time.
Eg : Gonococci develop resistance to penicillin.

14. Resistance may develop by :
a)Mutation
a1)Single step – E coli to rifampin
a2)Multiple step – Staphy. to rifampin
b)Gene transfer
b1)Conjugation - E coli to streptomycin
b2)Transduction – Resistance of stph.aureus
b3)Transformation – Pneumococci resistance to penicillin G

15. Beta lactam Antibiotics
Penicillins
 1st antibiotic to be used clinically in 1941.
Antibiotics having a beta lactam ring.
2 major groups include penicillins & cephalosporins.
Mechanism of action :
Interfere the synthesis of bacterial cell wall.
Bacterial cell wall has crosslinked peptidoglycans, which
provide rigidity & stability to cell wall.
Beta lactam antibiotics inhibit the transpeptidase-
cross linking doesn’t take place.

17. Such bacteria which divide in presence of beta lactam
antibiotic produce cell wall deficient forms.
They swell & burst –Bacterial lysis.
Preparations of Penicillin G
Duration of action of PnG increased by combining it
with poorly water soluble compounds like procaine,
benzathine..which are referred as repository penicllins.
Dose
Adult-500mg - t.i.d
Pediatric -250mg - t.i.d

18. Uses of penicillin G
Vincent angina,necrotizing gingivitis
Penumococcal infections-pnuemonia, meningitis
Diphtheria
Syphilis
Streptococcal infections-pharyngitis, rheumatic fever…

19. Adverse effects :
Local irritancy like pain at i.m injection site,nausea
on oral ingestion…
Direct toxicity to brain manifests as mental confusion,
convulsions & coma.
Hypersensitivity reactions
Jarisch – Herxheimer reaction :
Penicillin injection in syphilitic patient may produce
shivering,fever,myalgia…due to sudden release of
spirochetal lytic products.

20. Limitations of Penicillin G
1)Acid labile-orally not well effective
2)Short duration of action
3)Narrow spectrum of activity
4)Destroyed by penicillinase enzyme.
Classification of penicillins
a)Natural penicillins : Penicillin G,
Procain penicillin(0.6-1.2 MU),
benzathine penicillin(0.6-2.4 MU)
(PENIDURE).

21. b)Semisynthetic
b1)Acid resistant – Phenoxymethyl penicillin(250-500
mg,PENIVORAL)
b2)Penicillinase resistant – Methicillin,cloxacillin-250-500
mg (KLOX)
b3)Extended spectrum penicillins : Amoxicillin-250-500 MU
(Mox500,Novomox,Moxkid) , ampicillin-250-500mg(AMPILIN)

22. B4)beta lactamase inhibitors – Clavulanic acid
It has beta lactam ring but no antibacterial activity of
its own.
Clavulanic acid combine with amoxicillin which have
similar half life (AUGMENTIN-
250mg amoxicillin+ 125 mg clavulanic acid)
Bact.fragilis not responsive to amoxicillin alone but inhibited
by combination.
Addition of Clavulanic acid re-establishes the activity of
amoxicillin against beta lactamase producing Staph.aureus.
It can be used in Skin & soft tissue infections ,Gonorrhoea

23. Cephalosporins
All cephalosporins are bacteriocidal.
Mechanism of action similar to penicillin – cell wall
synthesis inhibition.

25. Uses :
1st generation – Cefazolin(ORIZOLIN) 1 g i.m / i.v ,30 min
before used for prophylaxis of bacterial endocarditis
before dental procedures & also used in odentogenic
infections.
2nd generation – Cefaclor(KEFLOR) -250mg useful in
orodental infections.
3rd generation – Used in severe gram negative
infections like community acquired pneumonia,
typhoid fever, gonorrhoea…
Adverse effects
Hypersensitivity
GIT disturbances-diarrhoea, vomiting…
Pain at site of infection.

26. Tetracyclines
Class of antibiotics having nucleus of 4 cyclic rings.
Mechanism of action
:
They are primarily
bacteriostatic
They inhibit protein
synthesis by binding to 30S
ribosome .
Thus interfere the binding
of aminoacyl tRNA to the
acceptor site of mRNA

27. Doses
Tetracycline(HOSTACYCLIN) – 250-500 mg – q.i.d
Doxycycline (TETRADOX)– 100-200 mg – o.d
Uses
In initial treatment of mixed infections.
1st choice of drugs in :
a)Venereal diseases
b)Atypical pneumonia
c)Cholera
2nd choice drugs :
To azithromycin for pneumonia,gonorrhoea & chancroid

28. Adverse effects
Irritative effects – nausea,vomiting,diarrhoea
Liver damage - In pregnant women may precipitate
acute hepatic necrosis.
All tetracyclines except doxycycline,accumulate &
enhance renal failure.
Phototoxicity – Sunburn like skin lesions on exposed parts.
Teeth & bones – Calcium-tetracycline chelate may get
deposited in teeth & bone.
If given during pregnancy,brown discoloration of
deciduous teeth,which become susceptible to caries.
Hypersensitivity reactions
Superinfection eg-pseudomonas enterocolitis

29. Chloramphenicol
Broad spectrum antibiotic but use is limited due
to its dangerous side effect – bone marrow supression
Mechanism of action
Bind reversibly to 50S ribosomal subunits-prevent
peptide bond formation-thus inhibit protein synthesis.
Uses
Never use it for minor infections or those of unknown
etiology or infections treatable by other safer AMAs

30. Daily dose not exceed 2-3 g & duration of therapy
to be <2 weeks.
Typhoid fever
Bacterial meningitis – In combination with ampicillin.
Intraocular infections
Anaerobic infections – caused by B.fragilis
Adverse effects
Bone marrow supression
1)Dose depent reversible supression-anaemia,leucocytopenia
2)Idiosyncratic nondose related aplastic anaemia-fetal.
Gray baby syndrome in neonates-Due to reduced
degradation in liver-skin appears ashengray colour.
Hypersensitivity reactions

31. Sulphonamides
1st AMAs effective against pyogenic bacterial infections.
Bacteriostatic
Classification :
1)Short acting – Sulfadiazine-0.5g tab q.i.d
2)Intermediate acting – Sulfamethoxazole-1 g BD
3)Long acting – Sulfadoxine.
Mechanism of action
PABA is a Component of folic acid,which is
produced by the bacteria & needed
for growth and multiplication of bacteria
Sulfonamides are structural analogous of PABA.

32. As the human cell not produce folic acid,but utilize it,
They are unaffected by sulfonamides.
Pus & tissue extracts contains purines & thymidine
which decrease bacterial requirement for FA & antagonize
the sulfonamide action.
Sulfonamide may itself get incorporated to
form an altered folate which is metabolically
injurious.
Thus they inhibit bacterial folate synthesis-
FA not formed-bacteriostatic effect.

34. Doses
Sulfadiazine – 500mg –QID
Sulfamethoxazole – 1g- BD
Uses
Sodium salt of sulphacetamide used topically for
treatment of ophthalmic infections.
Silver sulfadiazine used topically for preventing
infection of burn wound.
Combined with trimethaprim,sulfamethoxazole is
used in many infections.
With pyrimethamine, certain sulfonamides are used for
malaria.

35. Adverse affects
Nausea,vomiting,epigastric pain
Hypersensiticity reactions
Hepatitis
Kernicterus in newborn
Cotrimoxazole is the fixed dose combination of
trimethoprim and sulfamethoxazole.
Optimum synergic effect seen at concentration ratio
20 : 1 (Sulphamethoxazole : Trimethoprim)
Used in UTI infections,Bronchitis,Typhoid fever…
Adverse effects are Skin rashes,GIT disturbances
Cotrimoxazole

36. Individually both sulfonamide & Trimethoprim are
bacteriostatic.But the combination become bactericidal
against many organisms.

37. Quinolones
1st quinolone nalidixic acid is a urinary antiseptic.
Fluoroquinolones are fluorinated analogoues of
nalidixic acid.
Classification :
1st generation fluoroquinolones – Ciprofloxacin,ofloxacin
2nd generation fluoroquinolones – Levofloxacin , moxifloxacin
Mechanism of action
They inhibit bacterial DNA synthesis – bactericidal.
They inhibit DNA gyrase thus blocking DNA replication
in gram negative bacteria.

38. Uses
Ofloxacin used in TB,leprosy
Moxifloxacin & levofloxacin are used in community
acquired pneumonia
UTI
Bacterial diarrhoea
Ciprofloxacin is the preffered drug for treatment
of typhoid fever
Chancroid
Adverse effects
Nausea,vomiting
Headache,insomnia,convulsions
Hypersensitivity reactions

39. Macrolids
Antibiotics having macrocyclic lactone ring with
attached sugers.
Erythromycin is the 1st member discovered.
Safer to use in pregnancy.
Mechanism of action
They are bacteriostatic at low and cidal at high
concentrations.
They inhibit protein synthesis by binding with 50S
subunit of ribosome.
Activity enhanced in alkaline medium.

40. Dose
Erithromycin : 250-500mg – oral – q.i.d
Clarithromycin (CLARIBID): 250 mg – b.d
Azithromycin(AZITHRAL) : 500mg - o.d
Uses
Alternative to penicillin to treat orodental infections.
 Prophylaxis of dental infections –gingivitis, peridontitis…
Drug of choice in : pneumonial infections, chlamydal
Infections,diphtheria,pertussis…

41. Adverse effects
Nausea,vomiting,epigastric pain
Hypersensitivity reactions like skin rashes…

42. Aminoglycosides
They have amino groups linked glycosidically to 2 or
more aminosugar residues.
Classification :
1)Systemic – Streptomycin,gentamycin,amikacin
2)Topical – Neomycin,framycetin.
Mechanism of action
They inhibit protein synthesis –bactericidal.
Streptomycin binds to 30S ribosomes but other
aminoglycosides bind to additional sites on 50S
subunit,as well as to 30S-50S interface.

43. Uses
Streptomycin is a 1st line drug in TB.
Gentamycin used in aerobic gram negative bacillary
infections.
Neomycin used only for local effect.
Adverse effects
Ototoxicity
Nephrotoxicity
Hypersensitivity reactions
Neuromuscular blocking effect

44. Antibiotic prophylaxis

45. Conclusion
Antibiotics exert their action by various methodes
which include ; inhibition of cell wall synthesis,Inhibit
protein synthesis…
AMAs used in combinations to obtain better results.
Selection of drug,dose,freequency of taking are all
affect the net result.
GIT problems,hypersensutuvity,toxicity are most
frequently encountered adverse effects.
Accuarate drug choice is important for better
treatment and prognosis.

46. Reference
1) Essentials of medical pharmacology : 7th edition , by
K.D.TRIPATHI
2) Pharmacology for dentistry : 3rd edition ;by Tara V
Shanbhag,Smita Shenoy,Veena Nayak