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Anti-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 – Systemic Antifungal 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 mycoses Anti-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 Pneumocystis Anti-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 infections Other Anti-fungals • Griseofulvin – Given orally; reaches target site through sweat – Inhibits cell division • Tolnaftate – Used for athlete's foot; action unknown Anti-protozoan Inhibition of Nucleic Acids • 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 milk Anti-protozoan Inhibition of Necessary Metabolites • Nifurtimox – Effective against Trypanosoma – Interferes with electron transport – Mild gastrointestinal upset Other Anti-protozoan Drugs • Quinine and Quinolines – Isolated from a Peruvian tree; replaced with synthetic versions – Exact mechanism of action unknown- inhibits protozoan metabolism – Chloroquine & mefloquine • Malaria treatment Anti-helminthic Drugs • Niclosamide – Prevents ATP generation • Tapeworms • Praziquantel – Causes tetanic contractions • Flukes • Ivermectin – Paralyzes worm • Intestinal roundworms and tissue nematodes Anti-viral Drugs • Available antiviral drugs effective specific type of virus – None eliminate latent viruses – – – – – – Attachment Un-coating Nucleic acid synthesis Protein synthesis Maturation Release Anti-viral Inhibition of Nucleic Acids • 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 Viral Proteins • Indinavir – Protease inhibitor- inhibit viral assembly/release • HIV • Amantadine – Inhibit viral un-coating • Flu • Zanamivar – Neuraminidase inhibitor- inhibit viral attachment • Flu Anti-microbial Resistance • • Mutations lead to resistance Resistance is transferred between cells – Resistance genes are often on plasmids or transposons • • Multi-drug-resistant pathogens Cross resistance • Mechanisms of antibiotic resistance 1. Drug inactivating enzymes 2. Decreased uptake of the drug 3. Alteration of target molecule 4. Increased elimination of the drug 5. 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 treatment