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Chapter 20, part B

Chapter 20, part B. Antimicrobial Drugs. Antifungal Drugs Inhibition of Ergosterol Synthesis. Polyenes Amphotericin B Azoles Miconazole Triazoles Allylamines. Figure 20.15. Antifungal Drugs Inhibition of Cell Wall Synthesis. Echinocandins Inhibit synthesis of  -glucan

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Chapter 20, part B

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  1. Chapter 20, part B Antimicrobial Drugs

  2. Antifungal DrugsInhibition of Ergosterol Synthesis • Polyenes • Amphotericin B • Azoles • Miconazole • Triazoles • Allylamines Figure 20.15

  3. Antifungal DrugsInhibition of Cell Wall Synthesis • Echinocandins • Inhibit synthesis of -glucan • Cancidas is used against Candida and Pneumocystis

  4. Antifungal DrugsInhibition of Nucleic Acids • Flucytocine • Cytosine analog interferes with RNA synthesis • Pentamidine isethionate • Anti-Pneumocystis; may bind DNA

  5. Antifungal DrugsInhibition of Microtubules (Mitosis) • Griseofulvin • Used for superficial mycoses • Tolnaftate • Used for athlete's foot; action unknown

  6. Antiviral DrugsNucleoside and Nucleotide Analogs Figure 20.16a

  7. Acyclovir

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

  9. Antiviral DrugsEnzyme Inhibitors • Protease inhibitors • Indinavir • HIV • Inhibit attachment • Zanamivir • Relenza • Inhibit uncoating • Amantadine • Oseltamivir • Tamiflu • Interferons prevent spread of viruses to new cells • Viral hepatitis

  10. Antiprotozoan Drugs • Chloroquine • Inhibits DNA synthesis • Malaria - may require Malarone • Diiodohydroxyquin • Unknown • Amoeba • Metronidazole • Damages DNA • Entamoeba, Trichomonas

  11. Antihelminthic Drugs • Niclosamide • Prevents ATP generation • Tapeworms • Praziquantel • Alters membrane permeability • Flatworms • Pyantel pamoate • Neuromuscular block • Intestinal roundworms

  12. Antihelminthic Drugs • Mebendazole • Inhibits nutrient absorption • Intestinal roundworms • Ivermectin • Paralyzes worm • Intestinal roundworms

  13. Evaluation of Antimicrobials-Disk-Diffusion Test Figure 20.17

  14. MIC and MBC Action on growth after transfer to new media • MIC Minimal inhibitory concentration • MBC Minimal bactericidal concentration

  15. Broth Dilution Test Figure 20.19

  16. Figure 20.20

  17. 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.

  18. 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

  19. 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.

  20. Effects of Combinations of Drugs Figure 20.22

  21. 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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