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Antimicrobial DrugsPowerPoint PresentationHistory of AntibioticsSlide 4Slide 5Drug DiscoverySlide 7General Properties of antimicrobialsSlide 9The Action of Antimicrobial DrugsModes of actionSlide 12Slide 13Competitive InhibitorsSlide 15Side EffectsResistance of microbesAntibiotic ResistanceSlide 198 Attributes of an ideal antimicrobial agentSlide 21Inhibitors of cell wall SynthesisInhibitors of Protein SynthesisPlasma membraneInhibitors of Nucleic Acid SynthesisCompetitive inhibitors of the Synthesis of Essential MetabolitesAntifungalAntiviral drugsAntiprotozoan DrugsAntihelminthic DrugsSlide 31Nucleoside and Nucleotide AnalogsTests to Guide ChemotherapyBroth Dilution TestResistance to AntibioticsFrom LabEffects of Combinations of DrugsSlide 38Disk-Diffusion TestFuture of Chemotherapeutic AgentsSlide 41Slide 42Antimicrobial Drugs•Chemotherapy: Use of chemicals that do not harm the host yet kills others.•Chemotherapeutic agent: substance that is used in medicine.•Antimicrobial agents: Chemicals used to treat diseases caused by microbes.•Antibiotics: Produced by microbes to inhibit others•Synthetic drugs: Antimicrobials made in the lab•Semi Synthetic: synthetic or natural that is modified in the lab.History of Antibiotics•Paul Ehrlich- Sulfa that stains bacteria may be able to inhibit it as well. Predicted the rise of antimicrobials•1928 Fleming makes his observation•1940’s production of penicillin•In order to keep up with microbial resistance we must continually discover new antibiotics, but this is getting harder to do•1928 – Fleming discovered penicillin, produced by Penicill i um.•1940 – Howard Florey and Ernst Chain performed first clinical trials of penicillin.Figure 20.1Drug DiscoveryFigure 20.1General Properties of antimicrobials•Selective toxicity: Kills microbes not host•Has a spectrum of activity–Broad–Narrow–Which is better? –Why?Table 20.2The Action of Antimicrobial DrugsFigure 20.2Modes of action•Inhibition of cell wall synthesis–Pen•Disruption of cell membrane function–Polymyxins•Inhibition of protein synthesis–Chloramphenicol–Erythromycin–Tetracycline–StreptomycinThe Action of Antimicrobial DrugsFigure 20.4•Inhibition of nucleic acid synthesis–Rifamycin•Inhibitors of enzymatic function of primary metabolism–Competitive inhibition–Noncompetitive inhibition–Sulfonamides (sulfa drugs)Inhibit folic acid synthesisBroad spectrumCompetitive InhibitorsFigure 5.7bFigure 20.13Side Effects•Toxicity in host•Allergy in host•Disruption of normal microbiota•Birth defects in pregnancyResistance of microbes•When microbes no longer respond to an antibiotic•Resistance is acquired by–Non genetic means, basically evasion, grow in an area not exposed to antibiotic•Tuberculosis–Genetic resistance•A change in the chromosome or gain of a plasmid.•A variety of mutations can lead to antibiotic resistance.•Mechanisms of antibiotic resistance1. 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.Antibiotic Resistance•We humans will always have to find or create new antibiotics as microbes become resistant8 Attributes of an ideal antimicrobial agent1. Solubility in body fluids2. Selectively toxic3. Toxicity not easily altered4. Not allergenic5. Stability in body6. Resistance not easily acquired7. Long shelf life8. Reasonable cost•Drugs with all 8 characteristics are very very rare.Inhibitors of cell wall Synthesis•Ampicillin•Cephalosporin•Bacitracin•VancomycinInhibitors of Protein Synthesis•Streptomycin•Tetracycline•Clormphenicol•ErythromycinPlasma membrane•Polymyxin BInhibitors of Nucleic Acid Synthesis•Rifampin•ciprofloxacinCompetitive inhibitors of the Synthesis of Essential Metabolites•Trimethoprim-sulfamethoxozoleAntifungal•Amphotericin B•Griseofulvin•FlucytosineAntiviral drugs•Acyclovir•Ganciclovir•Indinavir•Alpha interferonAntiprotozoan Drugs•Chloroquine•Diiodohydroxyquin•MetronidazoleAntihelminthic Drugs•Niclosamide•What are these drugs, modes of action and side effects?Nucleoside and Nucleotide AnalogsFigure 20.16b ,cTests to Guide Chemotherapy•MIC: Minimal inhibitory concentration•MBC: Minimal bactericidal concentration•AntibiogramBroth Dilution TestFigure 20.19Resistance to AntibioticsFigure 20.20From Lab•How do antimicrobials work•How are they tested?Effects of Combinations of DrugsFigure 20.22Effects 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 aloneDisk-Diffusion TestFigure 20.17•Antimicrobial peptides–Broad-spectrum antibiotics •Nisin (lactic acid bacteria)•Magainin (frogs)•Cecropin (moths)Future of Chemotherapeutic AgentsFuture of Chemotherapeutic Agents•Antisense agents–Complementary DNA that binds to a pathogen's virulence gene(s) and prevents transcription–Fomivirsen to treat CMV retinitisFuture of Chemotherapeutic Agents•siRNA–Complementary RNA that binds mRNA to inhibit translationFigure


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