ANTIMICROBIAL THERAPY

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ANTIMICROBIAL THERAPY

• CHAPTER 13

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Chemotherapeutic Agents

• Antibiotics
• Synthetic Drugs

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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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Resistance to Drugs

• Chromosomal
• Plasmid borne

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Mechanisms of Drug Resistance

• Mutations in Target molecules
• Alterations in membrane permeability
• Enzyme development

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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
• 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