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Antifungal Drugs

Antifungal Drugs. Inhibition of ergosterol synthesis Polyenes Amphotericin B. Inhibition of cell wall synthesis Echinocandins Inhibit synthesis of  - glucan Cancidas is used against Candida and Pneumocystis. Azoles Miconazole Triazoles Allylamines

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Antifungal Drugs

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  1. Antifungal Drugs • Inhibition of ergosterol synthesis • Polyenes • Amphotericin B

  2. Inhibition of cell wall synthesis • Echinocandins • Inhibit synthesis of -glucan • Cancidas is used against Candida and Pneumocystis

  3. Azoles • Miconazole • Triazoles • Allylamines • For azole-resistant infections

  4. Inhibition of Nucleic Acids • Flucytocine • Cytosine analog interferes with RNA synthesis • Pentamidineisethionate • Anti-Pneumocystis; may bind DNA

  5. Other Antifungal Drugs • Griseofulvin • Inhibits microtubule formation • Superficial dermatophytes • Tolnaftate • Action unknown

  6. Antiviral Drugs • Nucleoside and nucleotide analogs

  7. Nucleoside and Nucleotide Analogs

  8. Antiviral Drugs • Protease inhibitors • Indinavir: HIV • Integrase inhibitors • HIV • Inhibit attachment • Zanamivir: Influenza • Block CCR5: HIV • Inhibit uncoating • Amantadine: Influenza

  9. Enzyme Inhibitors • Fusion inhibitors • Enfuvirtide: HIV • Inhibit attachment • Zanamivir: Influenza • Inhibit uncoating • Amantadine: Influenza

  10. Interferons • Prevent spread of viruses to new cells • Alpha interferon: Viral hepatitis • Imiquimod • Promotes interferon production

  11. Antiprotozoan Drugs • Chloroquine • Inhibits DNA synthesis • Malaria • Diiodohydroxyquin • Unknown mode of action • Amoebic diseases

  12. Antiprotozoan Drugs • Metronidazole • Damages DNA • Entamoeba, Trichomonas • Nitazoxanide • Interferes with metabolism of anaerobes

  13. Antihelminthic Drugs • Niclosamide • Prevents ATP generation • Tapeworms • Praziquantel • Alters membrane permeability • Flatworms

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

  15. Resistance to Antibiotics

  16. Antibiotic Resistance • A variety of mutations can lead to antibiotic resistance • Mechanisms of antibiotic resistance • Enzymatic destruction of drug • Prevention of penetration of drug • Alteration of drug's target site • Rapid ejection of the drug • Resistance genes are often on plasmids or transposons that can be transferred between bacteria • Misuse of antibiotics selects for resistance mutants. Misuse includes • Using outdated or weakened antibiotics • Using antibiotics for the common cold and other inappropriate conditions • Using antibiotics in animal feed • Failing complete the prescribed regimen • Using someone else's leftover prescription

  17. 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

  18. Future of Chemotherapeutic Agents • Antimicrobial peptides • Broad-spectrum antibiotics • Nisin (lactic acid bacteria) • Magainin (frogs) • Cecropin (moths) • Antisense agents • Complementary DNA that binds to a pathogen's virulence gene(s) and prevents transcription • Fomivirsen to treat CMV retinitis

  19. Future of Chemotherapeutic Agents • siRNA • Complementary RNA that binds mRNA to inhibit translation

  20. Assignment (test 3) • Explain why antiviral drugs are very difficult to develop. What are the possible targets that can be exploited in developing an antiviral drug? • In some cases, resistance to an antibiotic can spread very quickly through a microbial population. How does this happen? • Explain how β-lactam antibiotics kill bacteria. Why does penicillin kill only Gram positive bacteria that are actively growing? • Many pathogens have become resistant to antibiotics. What are the mechanisms of antibiotic resistance?

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