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Antimicrobial Drugs

Antimicrobial Drugs. Chemotherapy The use of drugs to treat a disease Antimicrobial drugs Interfere with the growth of microbes within a host Antibiotic Substance produced by a microbe that, in small amounts, inhibits another microbe

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Antimicrobial Drugs

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  1. Antimicrobial Drugs • Chemotherapy The use of drugs to treat a disease • Antimicrobial drugs Interfere with the growth of microbes within a host • Antibiotic Substance produced by a microbe that, in small amounts, inhibits another microbe • Selective toxicity A drug that kills harmful microbes without damaging the host

  2. 1928 – Fleming discovered penicillin, produced by Penicillium. • 1940 – Howard Florey and Ernst Chain performed first clinical trials of penicillin. • All three were awarded the Nobel Prize in Medicine in 1945 Figure 20.1

  3. Many Antibiotics come from Bacterial or Fungal Sources Table 20.1

  4. Table 20.2

  5. The Action of Antimicrobial Drugs • Disrupt Cell Wall synthesis or through damage • Disrupt Proteins synthesis • Disrupt Nucleic Acid synthesis or function • Disrupts essential metabolic enzymes-usually by competitive inhibition.

  6. The Action of Antimicrobial Drugs Figure 20.2

  7. The Action of Antimicrobial Drugs Figure 20.4

  8. Penicillins Figure 20.6

  9. Penicillinase Enzyme Allows Bacteria to be Resistant to Penicillin Figure 20.8

  10. Other Inhibitors of Cell Wall Synthesis • Cephlosporins-used Penicillin structure to synthesize antibiotics more effective on Gram Negative bacteria • Polypeptide antibiotics • Bacitracin • Topical application • Against gram-positives • Vancomycin • Glycopeptide • Important "last line" against antibiotic resistant S. aureus

  11. Other Inhibitors of Cell Wall Synthesis • Antimycobacterium antibiotics (TB, Leprosy) • Isoniazid (INH) • Inhibits mycolic acid synthesis • Ethambutol • Inhibits incorporation of mycolic acid

  12. Inhibitors of Protein Synthesis • Chloramphenicol • Broad spectrum • Binds 50S subunit, inhibits peptide bond formation • Aminoglycosides • Streptomycin, neomycin, gentamycin • Broad spectrum • Changes shape of 30S subunit

  13. Inhibitors of Protein Synthesis • Tetracyclines • Broad spectrum • Interferes with tRNA attachment • Erythromycin • Gram-positives • Binds 50S, prevents translocation Injury to the Plasma Membrane • Polymyxin B • Topical • Combined with bacitracin and neomycin in over-the-counter preparation

  14. Inhibitors of Nucleic Acid Synthesis • Rifamycin • Inhibits RNA synthesis • Antituberculosis • Quinolones and fluoroquinolones • Ciprofloxacin • Inhibits DNA gyrase • Urinary tract infections

  15. Competitive Inhibitors • Sulfonamides (Sulfa drugs) • Inhibit folic acid synthesis • Broad spectrum Figure 5.7

  16. Figure 20.13

  17. Antifungal DrugsInhibition of Ergosterol Synthesis • Ergosterol important part of fungal cell wall. Unique to fungi, therefore a good drug target Inhibition of Cell Wall Synthesis • Echinocandins • Inhibit synthesis of -glucan

  18. Antifungal DrugsInhibition of Nucleic Acids • Flucytocine • Cytosine analog interferes with RNA synthesis Antifungal DrugsInhibition of Microtubules (Mitosis) • Tolnaftate • Used for athlete's foot; action unknown

  19. Antiviral DrugsNucleoside and Nucleotide Analogs Figure 20.16a

  20. Antiviral DrugsNucleoside and Nucleotide Analogs Figure 20.16b, c

  21. Antiviral Drugs: Enzyme Inhibitors • Protease inhibitors • Indinavir • HIV • Inhibit attachment • Zanamivir • Influenza Antiprotozoan Drugs • Chloroquine • Inhibits DNA synthesis • Malaria

  22. Antibiotic Resistance • A variety of mutations can lead to antibiotic resistance. • Mechanisms of antibiotic resistance 1. Enzymatic destruction of drug 2. Prevention of penetration of drug 3. Alteration of drug's target site 4. Rapid ejection of the drug • Resistance genes are often on plasmids or transposons that can be transferred between bacteria.

  23. Antibiotic Resistance • Misuse of antibiotics selects for resistance mutants. Misuse includes: • Using outdated, weakened antibiotics • Using antibiotics for the common cold and other inappropriate conditions • Use of antibiotics in animal feed • Failure to complete the prescribed regimen • Using someone else's leftover prescription

  24. Disk-Diffusion Test Figure 20.17

  25. Chemical Methods of Microbial Control • Evaluating a disinfectant • Disk-diffusion method Figure 7.6

  26. MIC Minimal inhibitory concentration • MBC Minimal bactericidal concentration

  27. E Test Figure 20.18

  28. Effects of Combinations of Drugs • Synergism occurs when the effect of two drugs together is greater than the effect of either alone. • Antagonism occurs when the effect of two drugs together is less than the effect of either alone.

  29. Effects of Combinations of Drugs Figure 20.22

  30. The Future of Chemotherapeutic Agents • Antimicrobial peptides • Broad spectrum antibiotics from plants and animals • Squalamine (sharks) • Protegrin (pigs) • Magainin (frogs) • Antisense agents • Complementary DNA or peptide nucleic acids that binds to a pathogen's virulence gene(s) and prevents transcription

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