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Chapter 11Antimicrobial DrugsMechanisms of Antimicrobial Action•Goalof antimicrobial agent is to•Interfere with metabolism or structure of organism so that it cannot survive or reproduce•Microbicidal•Kills microbes•Can kill normal flora—potential for superinfection•Microbiostatic•Reversibly inhibits growth•Antimicrobial agentsuse different mechanisms of action toeither kill or inhibit microbial growth.•These mechanisms are varied and can target highly specific structures or metabolic functions necessary for the survival of the microorganism•These are divided into five basic categories:1.Cell wall synthesis inhibition2.Protein synthesis inhibition3.Nucleic acid synthesis inhibition4.Cell membrane disruption5.Metabolic antagonism/disruptionInhibition of Cell Wall Synthesis•Causes weakness of peptidoglycan layer•Vulnerable to lysis-Penicillin-CephalosporinsInhibition of Protein Synthesis•Disruption of translation at ribosome
•Ribosomes of eukaryotic cells not affected•Due to this difference, human cells are usually not affected by the inhibitory actionof these agents because they selectively act against bacteriaInhibition of Nucleic Acid Synthesis•Disruption of DNA and RNA synthesis•Complexity of metabolic process leads to disruption at many points-Disruption of the synthesis of nucleotide components-Inhibition of DNA replication-Interference with RNA transcription•Competitive inhibition—isprocess mimicking the normal substrate of an enzyme When these agents are supplied to the cell in high concentrations they will substitute for the true substrate of an important enzyme, thus preventing the enzyme from producing a needed product and causing the metabolism of the cell to slow or stop.•Examples: sulfonamides and trimethoprimDisruption of Plasma Membrane•Affects transport in/out of cell•Weakens cell’s physical integrity•Can affect prokaryotic and eukaryotic cells•Because all microorganisms (except for viruses) share the same basic plasma membrane structure, these agents are useful against both bacteria and fungi.Inhibition of Metabolic Pathways•Antimicrobial agentsdisrupt the metabolic pathways involved in the synthesis of proteins and nucleic acids, but can affect numerous cellular metabolic processes that can lead to cell death.•Disruption of numerous cellular metabolic processes•Disruption of enzyme activity/production
•Disruption of essential metabolic compoundsCharacteristics of Antimicrobial AgentsAlmost all antimicrobial agents share a set of common characteristics that are important to remember when selecting a drug for treatment•Spectrum of action•Selective toxicity•Microbicidal vs. microbiostatic•Delivery to infection site•Solubility and potency•Time it remains active•Degree of resistanceCharacteristics of Antimicrobial Agents (Cont(.