Antimicrobial DrugsSlide 2Slide 3DefinitionsSlide 5Slide 6The Action of Antimicrobial DrugsProtein Synthesis InhibitorsSlide 9Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis: PenicilinsPenicillinsAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis:CephalosporinsAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis: PolypeptidesAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis: Anti-MycobacterialsSlide 15Antibacterial Antibiotics Injury to the Plasma MembraneSlide 17Antibacterial Antibiotics Inhibitors of Nucleic Acid SynthesisSlide 19Antibacterial Antibiotics Competitive InhibitorsSlide 21Slide 22Antifungal Drugs Damage through ErgosterolAntifungal Drugs Inhibition of Cell Wall SynthesisOther Antifungal DrugsSlide 26Antiviral Drugs Nucleoside and Nucleotide AnalogsSlide 28Antiviral Drugs Enzyme InhibitorsSlide 30Antiprotozoan DrugsAntihelminthic DrugsSlide 33Slide 34Antibiotic ResistanceSlide 36Effects of Combinations of DrugsThe Future of Chemotherapeutic AgentsSlide 39Antimicrobial Drugs•History•Some definitions•Mechanisms of Action or Antibacterials•Protein synthesis inhibitors•Cell wall synthesis inhibitors•Plasma membrane-injuring agents•Nucleic acid inhibitors•Metabolic/enzyme inhibitors•Antifungals•Antivirals•Antiprotozoan drugs•Antihelminthics•Antibiotic Resistance•1928 – Fleming discovered penicillin, produced by Penicillium.•1940 – Howard Florey and Ernst Chain performed first clinical trials of penicillin.Figure 20.1Table 20.1Definitions•Chemotherapy The use of drugs to treat a disease•Antimicrobial drugs Interfere with the growth of microbes within a host•Antibiotic Substance produced by a microbe that, in small amounts, inhibits another microbe•Selective toxicity A drug that kills harmful microbes without damaging the host•Bacteriostatic/ Modes of action that either kill or bacteriocidal inhibit growth•Spectrum of activity Range of effect within or between groups of microbes; narrow vs. broad-spectrumTable 20.2Antimicrobial Drugs•History•Some definitions•Mechanisms of Action of Antibacterials•Protein synthesis inhibitors•Cell wall synthesis inhibitors•Plasma membrane-injuring agents•Nucleic acid inhibitors•Metabolic/enzyme inhibitors•Antifungals•Antivirals•Antiprotozoan drugs•Antihelminthics•Antibiotic ResistanceThe Action of Antimicrobial DrugsFigure 20.2Protein Synthesis InhibitorsFigure 20.4The Action of Antimicrobial DrugsFigure 20.2•Penicillins•Natural penicillins: G, V•Semisynthetic penicillins•“-cillin “ suffix•Carbapenems•MonobactamAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis: PenicilinsPenicillinsFigure 20.6•Cephalosporins•2nd, 3rd, and 4th generations more effective against gram-negativesAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis:CephalosporinsFigure 20.9•Polypeptide antibiotics•Bacitracin•Topical application•Against gram-positives•Vancomycin•Glycopeptide•Important "last line" against antibiotic resistant S. aureus (e.g. MRSA)Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis: Polypeptides•Antimycobacterium antibiotics•Isoniazid (INH)•Inhibits mycolic acid synthesis•Ethambutol•Inhibits incorporation of mycolic acidAntibacterial Antibiotics Inhibitors of Cell Wall Synthesis: Anti-MycobacterialsThe Action of Antimicrobial DrugsFigure 20.2•Polymyxin B•Topical•Combined with bacitracin and neomycin in over-the-counter preparationAntibacterial Antibiotics Injury to the Plasma MembraneThe Action of Antimicrobial DrugsFigure 20.2•Rifamycin•Inhibits RNA synthesis by RNA polymerase•Antituberculosis•Quinolones and fluoroquinolones•Ciprofloxacin•Inhibits DNA gyrase so blocks DNA polymerase•Urinary tract infectionsAntibacterial Antibiotics Inhibitors of Nucleic Acid SynthesisThe Action of Antimicrobial DrugsFigure 20.2•Sulfonamides (Sulfa drugs)•Inhibit folic acid synthesis•Broad spectrumAntibacterial Antibiotics Competitive InhibitorsFigure 5.7Figure 20.13TMZ - Trimethoprim + Sulfamethoxazole: SynergismAntimicrobial Drugs•History•Some definitions•Mechanisms of Action or Antibacterials•Protein synthesis inhibitors•Cell wall synthesis inhibitors•Plasma membrane-injuring agents•Nucleic acid inhibitors•Metabolic/enzyme inhibitors•Antifungals•Antivirals•Antiprotozoan drugs•Antihelminthics•Antibiotic Resistance•Leakage thorough binding ergosterol•Amphotericin B•Inibitors of Ergosterol Syntehsis•Miconazole, fluconazole•TriazolesAntifungal DrugsDamage through Ergosterol•Echinocandins•Inhibit synthesis of -glucan•Cancidas is used against Candida and PneumocystisAntifungal DrugsInhibition of Cell Wall Synthesis•Inhibition of Nucleic Acids •Flucytocine: cytosine analog interferes with RNA synthesis•Pentamidine isethionate for Pneumocytis : binds to DNA•Inhibition of Mitosis (microtubule beakers)•Griseofulvin•Used for superficial mycoses•Tolnaftate•Used for athlete's foot; action unknownOther Antifungal DrugsAntimicrobial Drugs•History•Some definitions•Mechanisms of Action or Antibacterials•Protein synthesis inhibitors•Cell wall synthesis inhibitors•Plasma membrane-injuring agents•Nucleic acid inhibitors•Metabolic/enzyme inhibitors•Antifungals•Antivirals•Antiprotozoan drugs•Antihelminthics•Antibiotic ResistanceAntiviral DrugsNucleoside and Nucleotide AnalogsFigure 20.16aAntiviral DrugsNucleoside and Nucleotide AnalogsFigure 20.16b, c•Protease inhibitors•Indinavir•HIV•Inhibits attachment•Zanamivir•Influenza•Inhibits uncoating•Amantadine•Influenza•Interferons prevent spread of viruses to new cells•Viral hepatitisAntiviral DrugsEnzyme InhibitorsAntimicrobial Drugs•History•Some definitions•Mechanisms of Action or Antibacterials•Protein synthesis inhibitors•Cell wall synthesis inhibitors•Plasma membrane-injuring agents•Nucleic acid inhibitors•Metabolic/enzyme inhibitors•Antifungals•Antivirals•Antiprotozoan drugs•Antihelminthics•Antibiotic Resistance•Chloroquine•Inhibits DNA synthesis•Malaria•Diiodohydroxyquin•Unknown•Amoeba•Metronidazole (Flagyl)•Damages DNA after becoming toxic from fermentation enzymes•Entamoeba, Trichomonas, Giardia (no mitochondria!)•(also works on obligately anaerobic bacteria like Clostrdium)Antiprotozoan Drugs•Niclosamide•Prevents ATP generation•Tapeworms•Praziquantel•Alters