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Chapter 13 Antimicrobial Drugs
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Chemotherapy: The use of drugs to treat a disease. Antimicrobial drugs: Interfere with the growth of microbes within a host. Antibiotic: A substance produced by a microbe that, in small amounts, inhibits another microbe. Selective toxicity: A drug that kills harmful microbes without damaging the host.
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1928: Fleming discovered penicillin, produced by Penicillium. 1940: Howard Florey and Ernst Chain performed first clinical trials of penicillin. Figure 20.1
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Table 20.1
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Table 20.2
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The Action of Antimicrobial Drugs Broad-spectrum Superinfection Bactericidal Bacteriostatic
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The Action of Antimicrobial Drugs Figure 20.2
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The Action of Antimicrobial Drugs Figure 20.4
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Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Penicillin –Natural penicillins –Semisynthetic penicillins
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Penicillins Figure 20.6
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Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Penicillin –Penicilinase-resistant penicillins –Extended-spectrum penicillins –Penicillins + -lactamase inhibitors –Carbapenems –Monobactam
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Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Figure 20.8
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Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Cephalosporins –2nd, 3rd, and 4th generations more effective against gram- negatives Figure 20.9
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Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Polypeptide antibiotics –Bacitracin Topical application Against gram-positives –Vancomycin Glycopeptide Important "last line" against antibiotic resistant S. aureus
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Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis Antimycobacterial antibiotics –Isoniazid (INH) Inhibits mycolic acid synthesis –Ethambutol Inhibits incorporation of mycolic acid
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Antibacterial Antibiotics Inhibitors of Protein Synthesis Chloramphenicol –Broad spectrum Binds 50S subunit, inhibits peptide bond formation Aminoglycosides –Streptomycin, neomycin, gentamycin Broad spectrum –Changes shape of 30S subunit
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Antibacterial Antibiotics Inhibitors of Protein Synthesis Tetracyclines –Broad spectrum Interferes with tRNA attachment Streptogramins –Gram-positives Binds 50S subunit, inhibits translation Figure 20.11
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Antibacterial Antibiotics Inhibitors of Protein Synthesis Macrolides –Gram-positives Binds 50S, prevents translocation Oxazolidinones –Linezolid Gram-positives –Binds 50S subunit, prevents formation of 70S ribosome Figure 20.12
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Antibacterial Antibiotics Injury to the Plasma Membrane Polymyxin B –Topical –Combined with bacitracin and neomycin in over-the-counter preparation.
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Antibacterial Antibiotics Inhibitors of Nucleic Acid Synthesis Rifamycin –Inhibits RNA synthesis –Antituberculosis Quinolones and fluoroquinolones –Ciprofloxacin –Inhibits DNA gyrase –Urinary tract infections
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Antibacterial Antibiotics Competitive Inhibitors –Sulfonamides (sulfa drugs) Inhibit folic acid synthesis Broad spectrum Figure 5.7
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Figure 20.13
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Antifungal Drugs: Inhibition of Ergosterol Synthesis Polyenes –Amphotericin B Azoles –Miconazole –Triazoles Allylamines Figure 20.15
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Antifungal Drugs: Inhibition of Cell Wall Synthesis Echinocandins –Inhibit synthesis of -glucan. –Cancidas is used against Candida and Pneumocystis.
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Antifungal Drugs: Inhibition of Nucleic Acids Flucytocine –Cytosine analog interferes with RNA synthesis. Pentamidine isethionate –Anti-Pneumocystis; may bind DNA.
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Antifungal Drugs: Inhibition of Microtubules (Mitosis) Griseofulvin –Used for superficial mycoses. Tolnaftate –Used for athlete's foot; action unknown.
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Antiviral Drugs: Nucleoside and Nucleotide Analogs Figure 20.16a
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Antiviral Drugs: Nucleoside and Nucleotide Analogs Figure 20.16b–c
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Antiviral Drugs: Enzyme Inhibitors Protease inhibitors –Indinavir HIV Inhibit attachment –Zanamivir Influenza Inhibit uncoating –Amantadine Influenza Interferons prevent spread of viruses to new cells Viral hepatitis Figure 13.2b
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Antiprotozoan Drugs Chloroquine –Inhibits DNA synthesis Malaria Diiodohydroxyquin –Unknown Amoeba Metronidazole –Damages DNA Entamoeba, Trichomonas Figure 12.17b
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Antihelminthic Drugs Niclosamide –Prevents ATP generation Tapeworms Praziquantel –Alters membrane permeability Flatworms Figure 12.27
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Antihelminthic Drugs Mebendazole –Inhibits nutrient absorption Intestinal roundworms Ivermectin –Paralyzes worm Intestinal roundworms Figure 12.29a
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Disk-Diffusion Test Figure 20.17
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E Test Figure 20.18
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MIC: Minimal inhibitory concentration. MBC: Minimal bactericidal concentration.
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Broth Dilution Test Figure 20.19
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Figure 20.20
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Antibiotic Resistance A variety of mutations can lead to antibiotic resistance. Mechanisms of antibiotic resistance 1.Enzymatic destruction of drug. 2.Prevention of penetration of drug. 3.Alteration of drug's target site. 4.Rapid ejection of the drug. Resistance genes are often on plasmids or transposons that can be transferred between bacteria.
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Antibiotic Resistance Misuse of antibiotics selects for resistance mutants. Misuse includes: –Using outdated or weakened antibiotics. –Using antibiotics for the common cold and other inappropriate conditions. –Use of antibiotics in animal feed. –Failure to complete the prescribed regimen. –Using someone else's leftover prescription.
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Effects 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 alone.
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Effects of Combinations of Drugs Figure 20.22
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The Future of Chemotherapeutic Agents Antimicrobial peptides –Broad spectrum antibiotics from plants and animals Squalamine (sharks) Protegrin (pigs) Magainin (frogs) Antisense agents –Complementary DNA or peptide nucleic acids that binds to a pathogen's virulence gene(s) and prevents transcription.
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