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ANTIMICROBIAL THERAPY

ANTIMICROBIAL THERAPY. CHAPTER 13. Chemotherapeutic Agents. Antibiotics: bacteriocidal vs bacteriostatic Synthetic Drugs vs natural product. History. Ancient remedies Ehrlich Domagk Fleming. Properties of Antimicrobial Agents. Selective Toxicity Spectrum of Activity Narrow Broad.

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ANTIMICROBIAL THERAPY

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  1. ANTIMICROBIAL THERAPY CHAPTER 13

  2. Chemotherapeutic Agents • Antibiotics: bacteriocidal vs bacteriostatic • Synthetic Drugs vs natural product

  3. History • Ancient remedies • Ehrlich • Domagk • Fleming

  4. Properties of Antimicrobial Agents • Selective Toxicity • Spectrum of Activity • Narrow • Broad

  5. Spectrum of Activity

  6. Drug Mechanisms of Action • Inhibition of Cell Wall Synthesis • Disruption of Cell Membrane Function

  7. Drug Mechanisms of Action • Inhibition of Protein Synthesis • Inhibition of Nucleic Acid Synthesis • Antimetabolites

  8. Summary of Targets

  9. Side Effects • Toxicity • Allergy • Disruption of Microflora

  10. Classes of antibiotics • Aminoglycosides • Tetracyclines • Sulfonamides • Quinolones • Polypeptides • B-lactams • Macrolides • Glycopeptides • Cephalosporins

  11. aminoglycosides kanamycin, neomycin, amikacin Binds 30 S ribosome

  12. tetracyclines Tetracycline, Doxycycline Binds 30 S ribosome

  13. sulfanamides Sulfacetamide Trimethoprim Sulfamethizole Folate synthesis inhibition. They are competitive inhibitors of the enzyme

  14. B-lactams Amoxicillin Carbenicillin Penicillin Ampicillin disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.

  15. quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme

  16. polypeptides Inhibits isoprenyl pyrophosphate bacitracin Polymyxin B Interacts with the bacterial cytoplasmic membrane, changing its permeability.

  17. macrolides Azithromycin Clarithromycin Spectinomycin Erythromycin Binds to 50s ribosome

  18. Glycopeptides Vancomycin- last resort drug inhibiting peptidoglycan synthesis

  19. cephalosporins Cefaclor Cefalexin Ceftobiprole Cefotaxime Same mode of action as other beta-lactam antibiotics: disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.

  20. Resistance to Drugs • Chromosomal - Klebsiella B lactamases • Plasmid borne - ribosomal protein mutations

  21. Mechanisms of Drug Resistance • Mutations in Target molecules • Alterations in membrane permeability • Enzyme development

  22. Fig. 27-27 Phosphorylation -Lactamase Adenylation Penicillin Streptomycin Acetylation Chloramphenicol

  23. Table 27-7

  24. Mechanisms of Drug Resistance • Enzyme Activity Changes • Alterations in Anabolic Pathways

  25. Generations of Drugs • First/Second/Third Line Drugs • Cross Resistance

  26. Limiting Drug Resistance • Effective Drug Concentrations • Simultaneous Drug Administration • Synergism - clavulanic acid • Antagonism - • Restricting Drug Prescriptions

  27. Determining Microbial Sensitivities • Disk Diffusion Method • Dilution Method • Serum Killing Power • Automated Methods

  28. Solubility Selective toxicity Stable toxicity level Allergenicity Tissue stability Resistance Acquisition Shelf Life Cost Ideal Antimicrobial Attributes

  29. Antibacterials — Cell Wall Target • Penicillins

  30. Antibacterials — Cell Wall Target • Cephalosporins • Carbapenems

  31. Antibacterials — Cell Membrane Target • Polymyxins

  32. Antibacterials — Protein Synthesis Inhibition • Aminoglycosides • Tetracyclines • Chloramphenicol • Macrolides Insert Fig. 13.13

  33. Antibacterials — Nucleic Acid Synthesis Inhibition • Rifampin • Quinolones

  34. Antibacterials — Antimetabolites • Sulfonamides • Isoniazid • Ethambutol • Nitrofurans

  35. Antifungals • Imidazoles • Polyenes • Griseofulvin

  36. Antifungals • Flucytosine • Tolnaftate • Terbinafine

  37. Antivirals • Nucleotide analogs

  38. Antivirals • Amantidine/Rimantidine • Interferons/Immunoenhancers

  39. Antiprotozoan Drugs • Quinine/derivatives • Metronidazole • Pyrimethamine • Suramin

  40. Antihelminthic Drugs • Niclosamide • Mebendazole • Ivermectin

  41. Special Drug Resistance Problems

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