Term
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Definition
| • Chemicals that affect physiology in any manner |
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Term
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Definition
| drugs that act against diseases |
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Term
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Definition
| drugs that treat infections |
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Term
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Definition
| antimicrobial agents produced by microorganisms that kill or inhibit the growth of other microbes |
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Term
| The History of Antimicrobial Agents |
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Definition
• Paul Ehrlich
– “Magic Bullets”
– Arsenic compound
that was used to
treat syphilis
• Alexander Fleming
– Penicillin released from Penicillium fungus inhibited the growth of Staphylococci growing on a plate |
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Term
| The History of Antimicrobial Agents |
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Definition
• Gerhard Domagk
– Sulfanilamide
– First antimicrobial agent used to treat wide array of infections
• Semisynthetics and synthetics |
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Term
| Mechanisms of Antimicrobial Action |
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Definition
• Key is selective toxicity
• Antibacterial drugs constitute largest number and diversity of antimicrobial agents
• Fewer drugs to treat eukaryotic infections
• Even fewer antiviral drugs |
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Term
| Inhibition of cell wall synthesis- |
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Definition
| – Penicillins, cephalosporins, vancomycin, penems |
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Term
| Inhibit Protein synthesis- |
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Definition
– 50s inhibitors: Eyrthromycin, clindamycin, chloramphenicol
– 30s inhibitors: Tetracyclines, aminoglycosides |
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Term
| Inhibit Nucleic acid Metabolism- |
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Definition
| – Quinolones, rifampin, sulfa drugs |
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Term
| Alter Cell Membrane Permeability- |
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Definition
| – Nystatin, Amphotericin B, Polymyxins, |
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Term
Mechanisms of Antimicrobial Action
Inhibition of Cell Wall Synthesis |
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Definition
• Most common agents act by preventing cross-linkage of NAM subunits
• Most prominent in this group – beta-lactams; functional groups are beta-lactam rings
• Beta-lactams bind to enzymes that cross-link NAM subunits
• Bacteria have weakened cell walls and eventually lyse |
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Term
Inhibition of Cell Wall Synthesis
Inhibition of Cell Wall Synthesis
Inhibition of Cell Wall Synthesis |
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Definition
• Semisynthetic derivatives of beta-lactams (ampicillin, methicillin, etc.)
– More stable in acidic environments
– More readily absorbed
– Less susceptible to deactivation
– More active against more types of bacteria
• Simplest beta-lactams (monobactams) – effective only against aerobic Gram-negatives |
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Term
| Inhibition of Cell Wall Synthesis |
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Definition
• Vancomycin and cycloserine interfere with particular alanine-alanine bridges that link NAM subunits in many Gram-positives
• Bacitracin blocks secretion of NAG and NAM from cytoplasm
• Isoniazid and ethambutol disrupt formation of arabinogalactan-mycolic acid in mycobacterial species |
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Term
| Inhibition of Cell Wall Synthesis |
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Definition
• Prevent bacteria from increasing amount of peptidoglycan
• Have no effect on existing peptidoglycan layer
• Effective only for growing cells
• No effect on plant or animal cells; no peptidoglycan |
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Term
| Inhibition of Protein Synthesis |
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Definition
• Prokaryotic ribosomes are 70S (30S and 50S)
• Eukaryotic ribosomes are 80S (40S and 60S)
• Drugs can selectively target translation
• Mitochondria of animals and humans contain 70S ribosomes; can be harmful |
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Term
Inhibition of Protein Synthesis
Disruption of Cytoplasmic Membranes |
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Definition
• Some drugs become incorporated into cytoplasmic membrane and damage its integrity
• Amphotericin B (polyene) attaches to ergosterol found in fungal membranes
– Humans somewhat susceptible because cholesterol similar to ergosterol
– Bacteria lack sterols; not susceptible
• Polymyxin disrupts cytoplasmic membranes of Gram-negatives; toxic to human kidneys |
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Term
Disruption of Cytoplasmic Membranes
Inhibition of Metabolic Pathways |
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Definition
• When differences exist between metabolic processes of pathogen and host, antimetabolic agents can be effective
• Heavy metals inactivate enzymes
• Agents that rid body of parasitic worms by paralyzing them
• Drugs block activation of viruses
• Metabolic antagonists |
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Term
Inhibition of Metabolic Pathways
Inhibition of Metabolic Pathways |
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Definition
• Trimethoprim binds to enzyme involved in conversion of dihydrofolic acid to THF
• Humans obtain folic acid from diet; metabolism unaffected
• Antiviral agents can target unique aspects of viral metabolism
– Amantadine, rimantadine, and weak organic bases neutralize acidity of phagolysosome and prevent viral uncoating |
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Term
| Inhibition of Nucleic Acid Synthesis |
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Definition
• Several drugs function by blocking DNA replication or mRNA transcription
• Only slight differences between prokaryotic and eukaryotic DNA; drugs often affect both types of cells
• Some (actinomycin) are not normally used to treat infections; used in research and perhaps to slow cancer cell replication |
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Term
| Inhibition of Nucleic Acid Synthesis |
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Definition
• Compounds can interfere with function of nucleic acids (nucleotide analogs)
• Distort shapes of nucleic acid molecules and prevent further replication, transcription, or translation
• Most often used against viruses; viral DNA polymerases more likely to incorporate and viral nucleic acid synthesis more rapid than that in host cells
• Also effective against rapidly dividing cancer cells |
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Term
| Inhibition of Nucleic Acid Synthesis |
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Definition
• Quinolones and fluoroquinolones act against prokaryotic DNA gyrase; little effect on eukaryotes or viruses
• Other drugs bind to and inhibit action of RNA polymerase during transcription; rifampin |
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Term
| Prevention of Virus Attachment |
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Definition
• Attachment can be blocked by peptide and sugar analogs of attachment or receptor proteins (attachment antagonists)
• Still in developmental stage |
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Term
| Ideal Antimicrobial Agent |
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Definition
• Readily available
• Inexpensive
• Chemically stable
• Easily administered
• Nontoxic and nonallergenic
• Selectively toxic against wide range of pathogens |
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Term
| Evaluation of Antimicrobial |
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Definition
• Spectrum of action
• Efficacy
– Dosages required to be effective
– Routes of administration
– Overall safety
• Side effects |
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Term
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Definition
• Broad-spectrum antimicrobials may allow for secondary or superinfections to develop
• Killing of normal flora reduces microbial antagonism |
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Term
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Definition
• Ascertained by
– Diffusion susceptibility tests
– Minimum inhibitory concentration test
– Minimum bactericidal concentration test |
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Term
Antimicrobials
Routes of Administration |
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Definition
• Topical application of drug if infection is external
• Oral – simplest; lower drug concentrations; no reliance on health care provider; patients do not always follow prescribing information
• Intramuscular – requires needle for administration; concentration never as high as IV administration
• Intravenous – requires needle or catheter; drug concentration diminishes as liver and kidneys remove drug from circulation
• Must know how antimicrobial agent will be distributed to infected tissues |
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Term
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Definition
• Three main categories of side effects:
– Toxicity
– Allergies
– Disruption of normal microbiota |
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Term
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Definition
• Exact cause of many adverse reactions poorly understood
• Drugs may be toxic to kidneys, liver, or nerves
• Considerations needed when prescribing drugs to pregnant women |
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Term
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Definition
• Although allergic reactions are rare, they may be life threatening
• Anaphylactic shock |
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Term
| Disruption of Normal Microbiota |
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Definition
• May result in secondary infections
• Overgrowth of normal flora – superinfections
• Of greatest concern for hospitalized patients |
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Term
| The Development of Resistant Organisms in Populations |
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Definition
• Some are naturally, partially or completely resistant
• Resistance by bacteria acquired in 2 ways
– New mutations of chromosomal genes
– Acquisition of R-plasmids via transformation, transduction, and conjugation |
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Term
| Multiple Resistance and Cross Resistance |
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Definition
• Pathogen can acquire resistance to more than one drug at a time
• Common when R-plasmids exchanged
• Develop in hospitals and nursing homes; constant use of drugs eliminates sensitive cells
• Superbugs
• Cross resistance |
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Term
Drug Inactivation by Modification:
Retarding Resistance |
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Definition
• High concentrations of drug maintained in patient for long enough time to kill all sensitive cells and inhibit others long enough for immune system to destroy
• Use antimicrobial agents in combination; synergism vs. antagonism
• Limit use of antimicrobials to necessary cases
• Development of new variations of existing drugs (novel side chains added to original molecule)
– Second-generation drugs
– Third-generation drugs |
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