Antibiotics PDF
Antibiotics PDF
Prepared by
Mr. Dharmendrasinh A Baria
Assistant professor
Department of Pharmaceutical Chemistry
Smt. S. M. Shah Pharmacy college, Amsaran
Introduction
Cis stereochemistry
Thiazolidine ring
H H S CH 3
R C HN C C
Variable group C CH 3
O C N
C H
O
Beta lactum ring
COO- Free carboxylate
Bicyclic ring system sysyem is essential
•Acid unstable.
•Parenteral route.
penicillinase enzyme.
• AMPICILLIN
• Acid stable.
• AMOXICILLIN
• β-hydroxy ampicillin.
• Non toxic.
Other Derivatives
Ticarillin
Piperacillin Carbenicillin
Mezlocillin
Azlocillin
STRUCTURAL ACTIVITY RELATIONSHIP
Resistance against Penicillin
•Natural
•Target enzymes and PBPs are deeply located (Lipoprotein barrier in –ve)
•PBPs of organisms have low affinity for penicillin
•Acquired
•Production of Penicillinase (Beta-Lactamase) enzyme, (>300 subtypes).
Common organisms producing Beta-Lactamase are
•Staphylococcus
•Bacillus subtilis
•Gonococci
•E. coli
•Enterococci
•Haemophilus influenza
•Loss or alteration of Porin channels in gram negative
•Modification of penicillin binding proteins (PBPs)- having low affinity .
•Activation of antibiotic efflux mechanism- Some gram negative bacteria
Adverse effects
General
•Hypersensitivity reactions (including Anaphylaxis)
•More with procaine penicillin,
•Intradermal Skin sensitivity test
•Major Determinant (Penicilloyl moiety in terms of amount) is responsible for
hypersensitivity other than anaphylaxis
•Minor determinants( Penicillamine and Penicillenate) are responsible for
anaphylaxis.
S Beta-lactamse S
N N
O H
O OH
• Clavulanic acid:
• Sulbactum:
from penicillins.
Tazobactum:
Co-administered with Piperacillin.
Has little or no antibacterial activity.
Cephalosporins
• Cephalosporins were discovered shortly after penicillin entered
into widespread product, but not developed till the 1960’s.
Cephalosporin P
Cephalosporin N
Cephalosporin C
cephalothin
cephaloridine
cefadroxil
cefalexin cefradine
These drugs are very active against Gram-positive cocci (such as
Pneumococci, Streptococci, and Staphylococci).
They do not cross BBB.
2nd Generation Cephalosporins
Cefachlor
Cefamycin
Cefixime
Ceftriaxone Cefotaxime
Third-generation drugs exhibit the lest activity against gram-positive
bacteria, but most potent activity against gram-negative bacteria :
Cefpirome
Cefepime
Zwitterionic compounds.
Good affinity for the transpeptidase enzyme.
Low affinity for some β-lactamases.
Cross BBB and effective in meningitis.
5th Generation Cephalosporins
Ceftobiprole
Active against
• Methicillin-resistant -Staphylococcus aureus
• Penicillin-resistant - Streptococcus pneumoniae
Cephalosporins advantages over penicillins
Decreased allergenicity.
β-lactamases.
Streptomyces cattleya
failure.
without reaction
(Aztreonam)
Reference