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 For azole-resistant infections

Inhibition of Nucleic Acids Flucytocine Cytosine analog interferes with RNA synthesis Pentamidine isethionate Anti-Pneumocystis; may bind DNA

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

Antiviral Drugs Nucleoside and nucleotide analogs

Nucleoside and Nucleotide Analogs

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

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

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

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

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

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

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

Resistance to Antibiotics

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 Misuse includes Using outdated or weakened antibiotics Using antibiotics for the common cold and other inappropriate conditions Using antibiotics in animal feed Failing complete the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

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

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

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

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?