antimicrobial therapy
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ANTIMICROBIAL THERAPYCHAPTER 13
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Chemotherapeutic Agents
Antibiotics: bacteriocidal vs bacteriostatic
Synthetic Drugs vs natural product
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History
Ancient remedies
Ehrlich
Domagk
Fleming
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Properties of Antimicrobial Agents
Selective Toxicity
Spectrum of Activity– Narrow
– Broad
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Spectrum of Activity
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Drug Mechanisms of Action
Inhibition of Cell Wall Synthesis
Disruption of Cell Membrane Function
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Drug Mechanisms of Action
Inhibition of Protein Synthesis
Inhibition of Nucleic Acid Synthesis
Antimetabolites
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Summary of Targets
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Side Effects
Toxicity
Allergy
Disruption of Microflora
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Classes of antibiotics Aminoglycosides Tetracyclines Sulfonamides Quinolones Polypeptides B-lactams Macrolides Glycopeptides Cephalosporins
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aminoglycosides
kanamycin, neomycin, amikacin
Binds 30 S ribosome
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tetracyclines
Tetracycline, Doxycycline
Binds 30 S ribosome
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sulfanamides
Sulfacetamide
Trimethoprim
Sulfamethizole
Folate synthesis inhibition. They are competitive inhibitors of the enzyme
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B-lactams
AmoxicillinCarbenicillinPenicillinAmpicillin
disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.
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quinolones
inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme
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polypeptides
bacitracin
Polymyxin B
Inhibits isoprenyl pyrophosphate
Interacts with the bacterial cytoplasmic membrane, changing its permeability.
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macrolides
Azithromycin
Clarithromycin
Spectinomycin
Erythromycin
Binds to 50s ribosome
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Glycopeptides
Vancomycin- last resort drug
inhibiting peptidoglycan synthesis
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cephalosporins
CefaclorCefalexinCeftobiproleCefotaxime
Same mode of action as other beta-lactam antibiotics: disrupt the synthesis of the peptidoglycan layer of bacterial cell walls.
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Resistance to Drugs
Chromosomal - Klebsiella B lactamases
Plasmid borne - ribosomal protein mutations
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Mechanisms of Drug Resistance
Mutations in Target molecules
Alterations in membrane permeability
Enzyme development
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Fig. 27-27
PhosphorylationAdenylation
Streptomycin
Chloramphenicol
-Lactamase
Penicillin
Acetylation
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Table 27-7
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Mechanisms of Drug Resistance
Enzyme Activity Changes
Alterations in Anabolic Pathways
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Generations of Drugs
First/Second/Third Line Drugs
Cross Resistance
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Limiting Drug Resistance
Effective Drug Concentrations
Simultaneous Drug Administration• Synergism - clavulanic acid• Antagonism -
Restricting Drug Prescriptions
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Determining Microbial Sensitivities
Disk Diffusion Method
Dilution Method
Serum Killing Power
Automated Methods
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Ideal Antimicrobial Attributes
Solubility
Selective toxicity
Stable toxicity level
Allergenicity
Tissue stability
Resistance Acquisition
Shelf Life
Cost
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Antibacterials — Cell Wall Target Penicillins
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Antibacterials — Cell Wall Target
Cephalosporins
Carbapenems
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Antibacterials — Cell Membrane Target
Polymyxins
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Antibacterials — Protein Synthesis Inhibition
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Insert Fig. 13.13
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Antibacterials — Nucleic Acid Synthesis Inhibition
Rifampin
Quinolones
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Antibacterials — Antimetabolites
Sulfonamides
Isoniazid
Ethambutol
Nitrofurans
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Antifungals
Imidazoles
Polyenes
Griseofulvin
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Antifungals
Flucytosine
Tolnaftate
Terbinafine
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Antivirals
Nucleotide analogs
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Antivirals
Amantidine/Rimantidine
Interferons/Immunoenhancers
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Antiprotozoan Drugs
Quinine/derivatives
Metronidazole
Pyrimethamine
Suramin
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Antihelminthic Drugs
Niclosamide
Mebendazole
Ivermectin
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Special Drug Resistance Problems
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