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
Pentamidine isethionate
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 Integrase inhibitors
Indinavir: HIV
Integrase inhibitors
HIV
Inhibit attachment
Zanamivir: Influenza
Block CCR5: HIV
Inhibit uncoating
Amantadine: Influenza

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

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

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

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

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

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

15. Resistance to Antibiotics

17. 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Using outdated or weakened antibiotics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

18. 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

19. 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

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

21. 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?