Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download S. aureus
Document related concepts
no text concepts found
Transcript
• Antimicrobial Drugs 2008 Antimicrobial Drugs • 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 2008 • 1928 – Fleming discovered penicillin, produced by Penicillium. • 1940 – Howard Florey and Ernst Chain performed first clinical trials of penicillin. 2008 Figure 20.1 2008 Table 20.1 2008 Table 20.2 The Action of Antimicrobial Drugs • Broad-spectrum • Superinfection • Bactericidal • Bacteriostatic 2008 The Action of Antimicrobial Drugs 2008 Figure 20.2 The Action of Antimicrobial Drugs 2008 Figure 20.4 Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Penicillin • Natural penicillins • Semisynthetic penicillins 2008 Penicillins 2008 Figure 20.6 Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Penicillin • Penicilinase-resistant penicillins • Extended-spectrum penicillins • Penicillins + -lactamase inhibitors • Carbapenems • Monobactam 2008 Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis 2008 Figure 20.8 Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Cephalosporins • 2nd, 3rd, and 4th generations more effective against gram-negatives 2008 Figure 20.9 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 2008 Antibacterial Antibiotics Inhibitors of Cell Wall Synthesis • Antimycobacterium antibiotics • Isoniazid (INH) • Inhibits mycolic acid synthesis • Ethambutol • Inhibits incorporation of mycolic acid 2008 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 2008 Antibacterial Antibiotics Inhibitors of Protein Synthesis • Tetracyclines • Broad spectrum • Interferes with tRNA attachment • Macrolides • Gram-positives • Binds 50S, prevents translocation • Erythromycin • Gram-positives • Binds 50S, prevents translocation 2008 Antibacterial Antibiotics Inhibitors of Protein Synthesis • Streptogramins • Gram-positives • Binds 50S subunit, inhibits translation • Synercid • Gram-positives • Binds 50S subunit, inhibits translation • Oxazolidinones • Linezolid • Gram-positives • Binds 50S subunit, prevents formation of 70S ribosome 2008 Antibacterial Antibiotics Injury to the Plasma Membrane • Polymyxin B • Topical • Combined with bacitracin and neomycin in overthe-counter preparation 2008 Antibacterial Antibiotics Inhibitors of Nucleic Acid Synthesis • Rifamycin • Inhibits RNA synthesis • Antituberculosis • Quinolones and fluoroquinolones • Ciprofloxacin • Inhibits DNA gyrase • Urinary tract infections 2008 Antibacterial Antibiotics Competitive Inhibitors • Sulfonamides (Sulfa drugs) • Inhibit folic acid synthesis • Broad spectrum 2008 Figure 5.7 2008 Figure 20.13 Antifungal Drugs Inhibition of Ergosterol Synthesis • Polyenes • Amphotericin B • Azoles • Miconazole • Triazoles • Allylamines 2008 Figure 20.15 Antifungal Drugs Inhibition of Cell Wall Synthesis • Echinocandins • Inhibit synthesis of -glucan • Cancidas is used against Candida and Pneumocystis 2008 Antifungal Drugs Inhibition of Nucleic Acids • Flucytocine • Cytosine analog interferes with RNA synthesis • Pentamidine isethionate • Anti-Pneumocystis; may bind DNA 2008 Antifungal Drugs Inhibition of Microtubules (Mitosis) • Griseofulvin • Used for superficial mycoses • Tolnaftate • Used for athlete's foot; action unknown 2008 Antiviral Drugs Nucleoside and Nucleotide Analogs 2008 Figure 20.16a Antiviral Drugs Nucleoside and Nucleotide Analogs 2008 Figure 20.16b, c 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 2008 Antiprotozoan Drugs • Chloroquine • Inhibits DNA synthesis • Malaria • Diiodohydroxyquin • Unknown • Amoeba • Metronidazole • Damages DNA • Entamoeba, Trichomonas 2008 Antihelminthic Drugs • Niclosamide • Prevents ATP generation • Tapeworms • Praziquantel • Alters membrane permeability • Flatworms • Pyantel pamoate • Neuromuscular block • Intestinal roundworms 2008 Antihelminthic Drugs • Mebendazole • Inhibits nutrient absorption • Intestinal roundworms • Ivermectin • Paralyzes worm • Intestinal roundworms 2008 Disk-Diffusion Test 2008 Figure 20.17 E Test 2008 Figure 20.18 • MIC Minimal inhibitory concentration • MBC Minimal bactericidal concentration 2008 Broth Dilution Test 2008 Figure 20.19 2008 Figure 20.20 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. 2008 Antibiotic Resistance • Misuse of antibiotics selects for resistance mutants. Misuse includes: • Using outdated, 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 2008 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. 2008 Effects of Combinations of Drugs 2008 Figure 20.22 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 2008
Related documents