Antifungal DrugsInhibition of ergosterol synthesisPolyenes

Amphotericin B

Inhibition of cell wall synthesisEchinocandins

Inhibit synthesis of -glucanCancidas is used against Candida and Pneumocystis

AzolesMiconazoleTriazoles

AllylaminesFor azole-resistant

infections

Inhibition of Nucleic AcidsFlucytocine

Cytosine analog interferes with RNA synthesis

Pentamidine isethionateAnti-Pneumocystis; may bind DNA

Other Antifungal DrugsGriseofulvin

Inhibits microtubule formationSuperficial dermatophytes

TolnaftateAction unknown

Antiviral DrugsNucleoside and nucleotide analogs

Nucleoside and Nucleotide Analogs

Antiviral DrugsProtease inhibitors

Indinavir: HIVIntegrase inhibitors

HIVInhibit attachment

Zanamivir: InfluenzaBlock CCR5: HIV

Inhibit uncoatingAmantadine: Influenza

Enzyme InhibitorsFusion inhibitors

Enfuvirtide: HIVInhibit attachment

Zanamivir: InfluenzaInhibit uncoating

Amantadine: Influenza

InterferonsPrevent spread of viruses to new cells

Alpha interferon: Viral hepatitisImiquimod

Promotes interferon production

Antiprotozoan DrugsChloroquine

Inhibits DNA synthesis Malaria

DiiodohydroxyquinUnknown mode of action

Amoebic diseases

Antiprotozoan DrugsMetronidazole

Damages DNA– Entamoeba, Trichomonas

NitazoxanideInterferes with metabolism of anaerobes

Antihelminthic DrugsNiclosamide

Prevents ATP generation

Tapeworms

PraziquantelAlters membrane

permeability Flatworms

Antihelminthic DrugsMebendazole

Inhibits nutrient absorption

Intestinal roundworms

IvermectinParalyzes worm

Intestinal roundworms

Resistance to Antibiotics

Antibiotic ResistanceA variety of mutations can lead to antibiotic resistanceMechanisms of antibiotic resistance

1. Enzymatic destruction of drug2. Prevention of penetration of drug3. Alteration of drug's target site4. 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 Misuse includes Using outdated or weakened antibiotics Using antibiotics for the common cold and other inappropriate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 DrugsSynergism 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 AgentsAntimicrobial peptides

Broad-spectrum antibiotics Nisin (lactic acid bacteria) Magainin (frogs) Cecropin (moths)

Antisense agentsComplementary DNA that binds to a

pathogen's virulence gene(s) and prevents transcription

Fomivirsen to treat CMV retinitis

Future of Chemotherapeutic AgentssiRNA

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?