This document discusses different classes of antibiotics, their sources, mechanisms of action, and examples. It focuses on penicillins, providing details on: 1) Penicillin G is the first antibiotic used clinically in 1941 and is obtained from fungus Penicillium notatum. 2) Penicillins work by inhibiting cell wall synthesis in bacteria. 3) Semisynthetic penicillins were developed to address limitations of Penicillin G like stability, spectrum and resistance. These include methicillin, amoxicillin, and piperacillin. 4) Beta-lactamase inhibitors like clavulanic acid are used to overcome bacterial resistance to penicillins from beta-lactam

1. ANTIBIOTICS
Antibiotics are obtained from
Fungi
penicillins,cephalosporin,griseofulvin
Bacteria
polymyxin B,Tyrothricin
colistin,aztreonam,bacitracin
Actinomycetes
aminoglycosides,macrolides,tetracyclines
polyenes,chloramphenicol

2. CLASSIFICATION-
A) Chemical structure
Β-lactam antibiotics-
penicillins,cephalosporins,monobactams,carbapenems
Tetracyclins
Oxytetracycline,doxytetracycline
Nitrobenzene derivative- chloramphenicol
Aminoglycosides
Streptomycin,gentamycin,amikacin,neomycin

3. Macrolide antibiotics
Erythromycin,clarithromycin,azithromycin
Glycopeptide antibiotics
Vancomycin,teicoplanin
Lincosamide antibiotics
Lincomycin,clindamycin
Oxazolidinone- linezolid

4. Polypeptide antibiotics
Polymyxin-B, colistin,bacitracin
Polyene antibiotics
Nystatin,amphotericin-B
B. Mechanism of action
1. Inhibit cell wall synthesis
penicillins,cephalosporins,cycloserines
vancomycin,bacitracin

5. 2. Causes leakage from cell wall membrane
Polypeptide-polymyxins,colistin,bacitracin
Polyenes- amphotericin B,nystatin
3. Inhibit protein syntheis
tetracyclins,chloramphenicol,erythromycin,
clindamycin
4. Cause misreading of m-RNA code and affect
permeability
Aminoglycosides-streptomycin,gentamycin

6. SPECTRUM OF ACTIVITY
Narrow spectrum
penicillin G
streptomycin
erythromycin
Broad spectrum
tetracyclines
chloramphenicol

7. PENICILLINS
First antibiotic to be used clinically in 1941
Originally obtained from fungus
Penicillium notatum
Present source is a high yeilding mutant of
P. chrysogenum

8. CHEMISTRY AND PROPERTIES
1- Thiazolidine ring
2- β-lactam ring
CH C
CH3
CH3
CH
S
C NH
COOHC N
O
O
R
12
Benzyl side chain
PENICILLINS
Amide linkage

9. MECHANISM OF ACTION
- Inhibit transpeptidase so that cross linking
does not take place
-When bacteria divide in presence of β-lactam
antibiotics –cell wall deficient(CWD) forms are
produced
-because the interior of the bacterium is
hyperosmotic ,the CWD forms swell & burst
bacterial lysis

10. Lytic effect of these antibiotics may also be due to
derepression of some bacterial autolysins which
normally function during cell division
Penicillin G
Spectrum- narrow
active only against gram +ve bacteria
Cocci: Streptococci,Pneumococci
gram –ve cocci- Neisseria gonorrhoeae
N.meningitidis

11. Bacilli: gram +ve - Corynebacterium. Dephtheriae
clostridia tetani
garm –ve- Actinomyces israelii
BACTERIAL RESISTANCE
Many bacteria are inherently insensitive to PnG
Because in them the target enzyme & PBPs are located
deeper under lipoprotein barrier wher PnG is unable to
penetrate

12. Production of penicillinase
it is a narrow spectrum β-lactamase which opens the
β-lactam ring and inactivates PnG.
Some bacteria become Penicillin tolerant –their target
Enzymes are altered to have low affinity for penicillin
Gram –ve bacteria have porin channels located in their
outer membrane.some gram –ve bacteria become resistant
By loss or alteration of porin channels.

13. PHARMACOKINETICS
A-
PnG is acid labile-destroyed by gastric acid
absorption from i.m route is rapid & complete
D –
Reaches most of the body fluids
Penetration in CSF is poor
M-
Little metabolised because of rapid excretion
E-
Very rapid renal excretion

14. ADVERSE EFFECTS
Local irritancy and direct toxicity
pain at i.m injection site
nausea on oral ingestion
Larger dose injected i.v –
Mental confusion
Muscular twitching
convulsions,coma.
Hypersensitivity
rash,itching & fever

15. USES
1.Streptococcal infections
2. Pneumococcal infections
3.Meningococcal infections
4.Gonorrhoea
5.Syphilis
6. Diphtheria
7.Tetanus

16. 8.Drug of choice for rare infections like
anthrax,rat bite fever,trench mouth
SEMISYNTHETIC PENICILLINS
Shortcomings of PnG
-Poor oral efficacy
-Suseptibility to penicillinase
-Narrow spectrum of activity
-Hypersensitivity reactions

17. CLASSIFICATION
1.Acid resistant alternative to PnG
phenoxymethyl penicillin(Penicillin V)
2.Penicillinase-resistant penicillins
methicillin,cloxacillin
3.Extended spectrum penicillins
a) aminopenicillins: ampicillin.bacampicillin,amoxicillin
b) carboxypenicillins: carbenicillin,ticarcillin
c) ureidopenicillins: piperacillin,mezlocillin
β-lactamase inhibitors
Clavulanic acid,sulbactum,tazobactum

18. 1.Acid resistant alternative to PnG
-acid stable
-oral absorption better
-antibacterial spectrum identical to PnG
-but it is1/5 as active against Neisseria
2.Penicillinase-resistant penicillins
-these have side chains that protect the β-lactam
ring from attack by staphylococcal penicillinase
Methecillin-
penicillinase resistant but not acid resistant

19. Cloxacillin-
Highly penicillinase resistant as well as acid resistant
3. Extended spectrum penicillins
Effective against gram-ve bacilli
1.Aminopenicillins
-These have amino group in side chain
-prodrugs
-none is resistant to penicillinase

20. AMPICILLIN
Uses
-UTI
-RTI
-Meningitis
-Gonorrhoea
BACAMPICILLIN
Ester prodrug of ampicillin
Completely absorbed from g.i.t
AMOXICILLIN
Close congener of ampicillin
Not a prodrug
Oral absorption is better

21. 2. CARBOXYPENICILLINS
-active against pseudomonas aeruginosa & proteus
- Carbenicillin is neither penicillinase resistant nor
acid resistant
-inactive orally
3.UREDOPENICILLINS
Piperacillin
-8 times more active than carbenicillin
-used mainly in immunocompromised patients
having serious gram-ve infections

22. BETA-LACTAMASE INHIBITORS
Clavulanic acid
Obtained from streptomyces clavuligerus
Has β lactam ring but no antibacterial activity