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Controlling Microbial Growth in the Body. Antimicrobial Drugs. Antimicrobial Drugs. History of Antimicrobial Agents Chemotherapy Paul Ehrlich 1854-1915- Magic Bullets Alexander Fleming 1881-1955- Antibiotics. Antimicrobial Drugs. Mechanisms of Antimicrobial Action Selective Toxicity
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Controlling Microbial Growth in the Body Antimicrobial Drugs
Antimicrobial Drugs • History of Antimicrobial Agents • Chemotherapy • Paul Ehrlich 1854-1915- Magic Bullets • Alexander Fleming 1881-1955- Antibiotics
Antimicrobial Drugs • Mechanisms of Antimicrobial Action • Selective Toxicity • Drugs that Inhibit Cell Wall Synthesis • Prevent synthesis of the polysaccharide, Peptidoglycan that makes up the bacterial cell wall • e.g. penicilins, cephalosporins, vancomycin • All penicillins consist of 3 parts • Thiazolidin • Beta-lactams • Variable side chain- group
Antimicrobial Drugs • Drugs that Inhibit Protein Synthesis • Differences in the ribosomes of prokaryotes and eukaryotes • Prokaryotes have 70S ribosomes and Eukaryotes have 80S ribosomes • Drugs selectively targets bacterial protein synthesis without significantly affecting eukaryotes • Examples of drugs include: tetracyclines and the aminiglycosides such as streptomycin and gentamycin • Aminiglycosides are composed of amino sugars that change the shape of 30S subunits of prokaryotic ribosomes
Antimicrobial Drugs • Disruption of Cytoplasmic Membranes • Agent becomes incorporated into prokaryotic membranes and damage integrity • E.g. Amphotericin B
Antimicrobial Drugs • Inhibition of Metabolic Pathways • Metabolism is sum total of all chemical reactions within an organism • Similarities and differences between prokaryotic and eukaryotic cells • Exploit differences • e.g., Heavy Metals inactivate enzymes, certain agents paralyze worms, and some prevent attachment of viruses
Antimicrobial Drugs • Sulfonamides are structural analogs of PABA (Para Amino Benzoic Acid) • Paba is crucial in synthesis of nucleotides • Analogs of paba such as sulfonamides are used to compete with paba.
Antimicrobial Drugs • Inhibition of Nucleic Acid Synthesis • Nucleotide Analogs • e.g., Quinolones act against prokaryotic DNA and Rifampin inhibit RNA Polymerases
Antimicrobial Drugs • Determining Efficacy of Drugs • Variety of Tests Used • 1. Diffusion Susceptibility Test • Called Kirby-Bauer Test • Measure zone of Inhibition • 2. Minimum Inhibitory Concentration (MIC) • Quantitative Expression of Drug Potency • Smallest amount of drug to inhibit growth and reproduction of pathogen • Determined by Broth Dilution Test
Antimicrobial Drugs • Minimum Bacteriocidal Concentration (MBC) • Subculture into drug-free media • Growth- bacteriostatic • No Growth- bacteriocidal • Lowest concentration of drug for which no growth occurs is MBC.