Anti-Fungal CompoundsSlide 2Antifungal Disruption of Cell MembraneSlide 4Anti-fungal Inhibition of Cell Wall SynthesisAnti-fungal Inhibition of Nucleic AcidsOther Anti-fungalsAnti-protozoan Inhibition of Nucleic AcidsAnti-protozoan Inhibition of Necessary MetabolitesOther Anti-protozoan DrugsAnti-helminthic DrugsSlide 12Anti-viral Inhibition of Nucleic AcidsAnti-viral Inhibition of Viral ProteinsAnti-microbial ResistanceSlide 16Slide 17Slide 18Slide 19Anti-Fungal Compounds•Eukaryotic pathogens–Similar cell structure and function•Many fungi are opportunistic–Fungal infections on the rise •Most have detoxification systems•Fungal infections (mycoses) may be:–Cutaneous•Dermatophytic–Subcutaneous–SystemicAntifungal Disruption of Cell Membrane•many target membrane sterols (ergosterol)•Polyenes–Produced by Streptomyces –Toxicity is a serious issue –Amphotericin B•Used for systemic mycoses –Nystatin•Effective topical treatment for cutaneous and subcutaneous mycoses•Azoles–Synthetic drugs –Fluconazole & Ketoconazole–Used to treat systemic mycoses, dermatophytic infections, cutaneous mycosesAnti-fungal Inhibition of Cell Wall Synthesis•Inhibition of β-glucan results in incomplete cell wall •Echinocandins–Caspofungin –used against many opportunistic mycoses•Candida, Aspergillus and PneumocystisAnti-fungal Inhibition of Nucleic Acids•Work on specific enzymes not in mammalian cells•Fluorocytocine–Synthetic drug –Cytosine analog interferes with RNA synthesis–Serious toxicity issues –Used to treat systemic yeast infectionsOther Anti-fungals•Griseofulvin–Given orally; reaches target site through sweat–Inhibits cell division•Tolnaftate–Used for athlete's foot; action unknown•Nitroimidazoles–Metronidazole•Effective against Trichomonas and Girardia•Effective against anaerobic bacteria •Activated by anaerobic metabolism•Alters DNA •Side effect – black, hairy tongue •Causes birth defects; passed in breast milkAnti-protozoan Inhibition of Nucleic Acids•Nifurtimox–Effective against Trypanosoma–Interferes with electron transport–Mild gastrointestinal upsetAnti-protozoan Inhibition of Necessary Metabolites•Quinine and Quinolines –Isolated from a Peruvian tree; replaced with synthetic versions–Exact mechanism of action unknown- inhibits protozoan metabolism–Chloroquine & mefloquine•Malaria treatment Other Anti-protozoan Drugs•Niclosamide–Prevents ATP generation•Tapeworms•Praziquantel–Causes tetanic contractions •Flukes•Ivermectin–Paralyzes worm•Intestinal roundworms and tissue nematodes Anti-helminthic Drugs•Available antiviral drugs effective specific type of virus–None eliminate latent viruses–Attachment–Un-coating–Nucleic acid synthesis–Protein synthesis –Maturation–ReleaseAnti-viral Drugs•Nucleoside/nucleotide analogs–Results in an increased mutation rate •Azidothymidine (AZT)–HIV•Ribavirin–Flu, respiratory syncytial virus, hepatitis •Acyclovir–Reduces frequency and severity of herpes outbreaks–Herpes viruses Anti-viral Inhibition of Nucleic Acids•Indinavir –Protease inhibitor- inhibit viral assembly/release •HIV•Amantadine –Inhibit viral un-coating•Flu•Zanamivar –Neuraminidase inhibitor- inhibit viral attachment •FluAnti-viral Inhibition of Viral Proteins•Mutations lead to resistance•Resistance is transferred between cells–Resistance genes are often on plasmids or transposons •Multi-drug-resistant pathogens•Cross resistanceAnti-microbial Resistance•Mechanisms of antibiotic resistance1. Drug inactivating enzymes2. Decreased uptake of the drug3. Alteration of target molecule4. Increased elimination of the drug5. Protecting the target•Misuse selects for resistant mutants–Using outdated, weakened antibiotics–Using antibiotics for inappropriate conditions–Use of antibiotics in animal feed–Failure to complete the prescribed regimen•Slowing emergence and spread of resistance–Responsibilities of healthcare workers•Increase efforts to prescribe antibiotics for specific organisms•Educate patients on proper use of antibiotics•Synergism–Responsibilities of patients•Follow instructions carefully•Complete prescribed course of