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Prof. R. K. Dixit
Pharmacology and Therapeutics
K. G. M. U. Lucknow
dixitkumarrakesh@gmail.com
Objectives
After completion of this lecture you will be able to
understand
– What are betalactam antimicrobials
– Mechanism of action
– Types of Penicillin, Uses, ADRs
– Classification of Cephalosporin, Uses, ADRs
– Members of Carbapenem and Monobactam, Uses, ADRs
•Have Beta-lactam ring
•Important groups are (PCcM) Paracetamol
Penicillins
Cephalosporins
Carbapenems
Monobactams
Broken by Amidase enzyme
Active material
Raw material for other
penicillin
Carbapenem Monobactam
•Obtained from
Penicillium notatum (Early)
Penicillium chrysogenum (Now, Better Yield)
•Original Penicillin –
•Penicillin G, Benzyl Penicillin ( R is Benzyl (CH2C6H5) )
Chemistry
•Penicillin nucleus consists of
•Thiazolidine ring (Ring A)-
•Sulphur containing with COOH (Carboxyl group),
•Beta lactam ring (Ring B) – (Broken by Betalactamase)
•Side chain is attached at position – 6- (NHCOR)
•Natural Penicillin is
•Benzyl penicillin or Penicillin G (PnG) and
it is
•Thermo and Acid labile
Penicillin Units
•Additional mechanism –
•Activation of autolysing enzymes
(Murein Hydrolase and Autolysins)
• In gram positive
• Thick layer of Peptidoglycans and teichoic acid (a polyol
phosphate polymer) surrounds the membrane.
• Peptidoglycans layer is easily accessible to Beta lactam antibiotics
• In gram negative
• Two membranes are present. (The cytoplasmic membrane and an
outer membrane with thin layer of Peptidoglycans sandwiched
between the two).
• The outer membrane consists of lipopolysaccharides with narrow
porin channels which function as a barrier to permeability of
antibiotics
• Penicillins which are hydrophilic in nature
(Ampicillin and Amoxicillin) can diffuse through
porin channels and show activity against negative.
•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)