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Antibiotics – History & Introduction :- PDF/PPT

Description

•History & Introduction
•Commercial Production of antibiotics
•Over view of Mechanism of action of various antibiotics
•Various methods of Classification of Antibiotics
• Understand the history of evolution of antibiotics as therapeutic agents
• Define the term “antibiotic”
• Explain how antibiotics are commercially produced
• Explain the general mode of action of various antibiotics
• Classify antibiotics based on various criteria
Antibiotics
• Historical background,
• Nomenclature,
• Stereochemistry,
• Structure activity relationship,
• Chemical degradation classification and important products of the following classes.

Unit:- 1
MEDICINAL CHEMISTRY – III

• Penicillin was discovered and introduced into therapy by Sir.
Alexander Fleming & Florey and Chain respectively
• Definition of Antibiotic
• Steps involved in commercial production of antibiotics
• Mechanism of action – overview
• Four methods of classification

History:
              Modern Antibiotic era
• Initiated by the accidental discovery of the anti-bacterial
  properties of Penicillin in 1929 by Sir Alexander Fleming
• Florey and Chain introduced Penicillin into therapy [1938]
• Definition (original) [By WAKSMAN (1942)]
• “ An antibiotic or antibiotic substance is a substance produced
  by micro-organisms, which has the capacity of inhibiting the
  growth and even of destroying other micro-organisms”




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               Introduction Contd…

Modern Definition:
• “ Any substance produced by a living organism that is capable
  of inhibiting the growth or survival of one or more species of
  micro-organisms in low concentrations”
• Modified by Medicinal Chemists to include the substances
  obtained from natural, semi-synthetic and synthetic sources




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                Introduction Contd…
Hence a substance is classified as an antibiotic if the following
conditions are met:
• It is a product of metabolism
• It is a synthetic product produced as a structural analogue of a
  naturally occurring antibiotic
• It antagonizes the growth or survival of one or more species of
  micro-organisms
• It is effective in low-concentrations


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    COMMERCIAL PRODUCTION: (of
           antibiotics)
The general scheme of commercial production of antibiotics for
medicinal use may be divided into six steps:
• Preparation of a pure culture of the desired organism for
  inoculation of the fermentation medium.
• Fermentation, during which the antibiotic is formed.
• Isolation of the antibiotic from the medium
• Purification
• Assays for potency, sterility, absence of pyrogens and other
  necessary data
• Formulation into acceptable and stable dosage forms.
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             MECHANISM OF ACTION
• Mechanisms of action of some common antibiotics are as follows:-
       Site of action   Antibiotic        Process interrupted           Type of
                                                                        activity
   1   Cell wall        Penicillins       Cell-wall cross linking       Bactericidal
                        Cephalosprins     Cell-wall cross linking       Bactericidal
                        Cycloserine                                     Bactericidal
                                          Synthesis of Cell wall peptides
                        Vancomycin        Muco-peptide synthesis        Bactericidal
                        Bacitracin        Muco-peptide synthesis        Bactericidal
   2   Cell membrane    Amphotericin B    Membrane function             Fungicidal
                        Nystatin          Membrane function             Fungicidal
                        Polymyxins        Membrane Integrity            Bactericidal
   3   Ribosomes        Chloramphenicol   Protein synthesis             Bactericidal
       50 S subunit     Erythromycin      Protein synthesis             Bactericidal
                        Lincomycins       Protein synthesis             Bactericidal
       30 S subunit     Aminoglycosides   Protein synthesis & fidelity  Bactericidal
                        Tetracyclines     Protein synthesis             Bacteriostatic
   4   Nucleic Acids    Actinomycin       DNA & mRNA synthesis          Pancidal
                        Griseofulvin      Cell division, microtubule    Fungicidal
                                          Assembly
       DNA and /or      Mitomycin         DNA synthesis                   Pancidal
       RNA              Rifampin          mRNA synthesis          www.remixeducation.in
                                                                          Bactericidal
    MECHANISM OF ACTION Contd…
“ ANTIBIOTICS THAT INTERFERE WITH THE METABOLIC SYSTEMS
FOUND IN MICRO-ORGANISMS AND NOT IN MAMALIAN CELLS
ARE THE MOST SUCCESSFUL ANTI-INFECTIVE AGENTS”
For example,
• Antibiotics that interfere with the synthesis of bacterial cell walls
  have a high potential for selective toxicity.
Cycloserine is an antimetabolite of D-Alanine, a constituent of
  bacterial cell wall.




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       MECHANISM OF ACTION Contd…
Many antibiotics like aminoglycosides, tetracyclines etc selectively
  interfere with microbial protein synthesis or nucleic acid synthesis
  like Rifampin.
Others like polymixins and polyenes, interfere with the integrity and
  function of microbial cell membranes.
• The agents may be a bactericidal or a bacteriostatic.
• This distinction is important for the treatment of serious, life-
  threatening infections, particularly if the natural defense
  mechanisms of the host are either deficient or overwhelmed by the
  infection – in such cases, a bactericidal is indicated.


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        CLASSIFICATION (of Antibiotics)
• Various criteria are used to classify ‘ Antibiotics’
I method:
Based on the clinical effectiveness, spectrum of activity and degree
of selectivity.
Class 1:- Those inhibiting only one group of micro-organisms
• “Narrow Spectrum Antibiotics” eg. Nystatin and Bacitracin.
• Exhibit a high degree of selectivity.
Class 2:- Those inhibit both “Gram +Ve” and “Gram -Ve” bacterial and
/or other intracellular organisms.
• “ Broad Spectrum Antibiotics” eg. Chloramphenicol and Tetracyclin.
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       CLASSIFICATION (of Antibiotics)
                 contd…
II method: based on the sources from which antibiotics are
  obtained. They can be classified as
a. Natural:- obtained from the large scale fermentation of micro-
   organisms.
  Eg. ‘ Bacitracin’ and ‘Polymixin’ are obtained from some bacilli.
  ‘Streptomycin’ and ‘Tetracycline’ are obtained from streptomyces
   species
b. Semi-synthetic:- The precursors of these antibiotics are obtained
from natural source. Synthetic method is utilized to produce the
analogues/derivatives of these precursors.

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        CLASSIFICATION (of Antibiotics)
                  contd…
For example: 6-Aminopenicillanic acid is obtained from the cultures
of P. Chrysogenum. During the commercial production of benzyl
penicillin (Penicillin G), Phenyl acetic acid is added to the medium in
order to get the product.
c.   Synthetic:- This class includes antibiotics which are having purely
     synthetic origin.
• For example: Chloramphenicol (a broad spectrum antibiotic),
  ciprofloxacin,etc



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       CLASSIFICATION (of Antibiotics)
                 contd…
III method: based on the differences in the mechanism of action.
A. Drugs that interferes with the biosynthesis of bacterial cell-wall
 Eg. Penicillins, Cephalosprins, Cycloserin, Bacitracin & Vancomycin.
B. Drugs that interfere in the functioning of Cytoplasmic membrane.
 Eg. Polymixins, Aphotericin B and Nystatin.
C. Drugs that interfere with the protein biosynthesis.
 Eg. Erythromycin, Lincomycins, Tetracyclines and Chloramphenicol.
D. Drugs that interfere with Nucleic acid biosynthesis
 Eg. Actinomycin, Griseofulvin and Rifampin.

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       CLASSIFICATION (of Antibiotics)
                 contd…
IV method: based on the chemical structure.
Β-lactam Antibiotics:
  Eg. Penicillins, Cephalosprins, Monobactams.
Aminoglycosides:
  Eg. Kanamycin, Streptomycin, Gentamycin, Neomycin, etc.
Tetracycline Antibiotics:
  Eg. Tetracycline, Chlortetracycline, Oxytetracycline, etc.



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        CLASSIFICATION (of Antibiotics)
                  contd…
Peptide Antibiotics:
  Eg. Amphomycin, Tyrothricin, Bacitracin, etc.
Macrolide Antibiotics:
  Eg. Erythromycin, Oleandomycin
Lincomycin:
  Eg. Lincomycin, Clindamycin, pirlimycin
Unclassified Antibiotics:
  Eg. Chloramphenicol, Rifamycin.
“Anti-fungal Antibiotics”
  Eg. Griseofulvin, Polyene Antibiotics (Amphotericin B, Nystatin, Candicidin)

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                         Summary
• Penicillin was discovered and introduced into therapy by Sir.
  Alexander Fleming & Florey and Chain respectively
• Definition of Antibiotic
• Steps involved in commercial production of antibiotics
• Mechanism of action - overview
• Four methods of classification
  • Subject:- Medicinal chemistry 3
  • Course:- B.pharm (pharmacy),
  • Semester:- 6th sem , sem :- 6

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