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40 Cards in this Set
- Front
- Back
What are the two bases for selective toxicity
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Structural differences in the target and permeability differences
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What are the three main steps of protein synthesis in bacteria
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Amino acid activation, Formation of 30S and 70S initiation complexes, and polypeptide chain synthesis
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What does amino acid activation involve
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Formation of charged tRNA
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What are the translational events of protein synthesis
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Recognition, peptidyl transfer, translocation, release
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What drugs inhibit amino acid activation
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There are none
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What drugs inhibit formation of initiation complexes
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Linezolid (Zyvox) is the only drug that inhibits formation of the 70S complex. In a class of antibiotics called oxazolidinones. It prevents the formation of the N-formylmethionyl-tRNA-mRNA-70S ribosomal ternary complex by binding to the 23S peptidyltransferase center of the 50S ribosomal subunit. It is bacteriostatic
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What drugs inhibit recognition
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Streptomycin and related aminoglycosides (kanmycin, tobramycin, gentamycin, neomycin, amikacin, paramomycin)
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What type of drugs are the aminoglycosides
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Broad spectrum, bactericidal antibiotics for both gram positive and negative. They target specific proteins in the 30S ribosomal subunit
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What is the mechanism of action of streptomycin
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At low concentrations, or in the case of ribosomes engaged in polypeptide elongation, streptomycin primarily causes misreading. Due to distortions of codons in the recognition region of the A-site
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What are streptomycin-dependent mutants
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Bacteria that require streptomycin binding to restore a mutationally altered recognition region to the proper conformation
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How does streptomycin kill bacteria
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Killing action is due to cyclic polysomal blockade. The drug does not prevent formation of a 70S initiation complex; however, once the complex is formed it is unstable and rapidly dissociates
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What is required for streptomycin to inhibit protein synthesis
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Some faulty protein synthesis due to misreading, facilitating drug entry into the cell
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What does streptomycin bind to
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The S12 protein of the 30S ribosomal subunit (Wikipedia says its the 23S rRNA bacterial ribosome)
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Why don't aminoglycosides harm the host
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Absence of their specific protein targets in host cell 40S ribosomal subunits. Also, they are not actively transported into euckaryotic cells
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How do the aminoglycosides differ from one another aside from their respective structures
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All have the same general mechanism of action, but they do not have common binding sites on the 30S ribosomal subunit. They also differ with respect to their spectra, their ability to enter bacterial cells, and their susceptibility to inactivation
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How can resistance to aminoglycosides develop
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Mutation of the target protein in the 30S ribosomal subunit; decreased uptake of the antibiotic; enzymatic modification of the antibiotic
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What do newer aminoglycosides bind to
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Both the 30S and the 50S ribosomal subunit
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What are the negative aspects of aminoglycoside therapy
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Resistance emerges with high frequency; Ototoxicity and nephrotoxicity; Action antagonized by anaerobiasis, acid pH, and polyvalent ions; ineffective against intracellularly localized bacteria
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What are the positive aspects of aminoglycoside therapy
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Rapid bactericidal effect in sensitive cells; Broad spectrum; slow development of resistance in newer drugs
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What are the characteristics of spectinomycin
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Not a true aminoglycoside. Bacteriostatic. Causes formation of unstable 70S, but does not cause misreading and does not inhibit polysomal ribosomes. Used against Beta-lactamase producing gonococci or to treat gonorrhea in patients allergic to penicillin
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What are the characteristics of the tetracyclines
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Broad spectrum, bacteriostatic. Effective against Chlamydia, Mycoplasma, Rickettsia, and other gram positive and negative bacteria. They bind to the 30S ribosomal subunit and inhibit binding of aminoacyl-tRNA to the A-site. Selective toxicity due to energy-dependent uptake of the drugs by bacteria. Useful against intracellular bacteria
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What are the inhibitors of peptidyl transfer
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Chloramphenicol, Lincomycin, and Clindamycin
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What type of drug is chloramphenicol
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Broad spectrum, bacteriostatic.
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What is the mechanism of action of chloramphenicol
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Binds reversibly to the 50S subunit and alters the tRNA at the P site
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What is the selective toxicity of chloramphenicol due to
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Inability to enter mitochondria.
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How is resistance to chloramphenicol achieved
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Plasmid encoded acetyltransferases catalyze the acetylation of the 3-hydroxy group, making it incapable of binding 50S. There can also be mutations in outer membrane porins
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What type of drugs are lincomycin and clindamycin
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Bacteriostatic, narrow spectrum
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What are lincomycin and clindamycin used for
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Effective in the treatment of infections caused by gram positive bacteria. Clindamycin is effective against staphylococci and anaerobic gram negative bacteria
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How is resistance to clindamycin achieved
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Methylation of 23S ribosomal RNA. This also results in resistance to erythromycin
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What antibiotics inhibit translocation
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Erythromycin, Azithromycin, clarithromycin, Telithromycin
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What are three macrolide antibiotics
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Erythromycin, azithromycin, clarithromycin
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What are the characteristics of macrolide drugs
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Macrocyclic lactone chemical structure. Bacteriostatic and bind with ribosomes from bacteria to prevent the production of proteins
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What is the mechanism of action of the macrolides
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Binding to 50S, which prevents peptidyl tRNA from returning to the P site from the A site. This prevents ejection of free deacylated tRNA from the P site
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How is resistance to the macrolides achieved
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Methylation of the 23S RNA of the 50S ribosome. Can also be due to hydrolysis of the lactone ring or active efflux of the drug
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What are the ketolide antibiotics (Telithromycin)
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New family of drugs. Bind with the exit tunnel of the large ribosomal subunit, thus blocking the exit of nascent polypeptides
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Why are the aminoglycosides ineffectual in the treatment of infections involving abscess formation
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They are not actively transported into eucaryotic host cells, so they can never reach the bacteria
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What would happen to the viability of a chloramphenicol-sensitive organism if it were washed free of the drug
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Growth would resume, since Chloramphenical reversibly binds 50S, upsetting peptidyl transfer
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Which of the antibiotics that inhibit protein synthesis have the 50S ribosomal subunit as their target
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Chloramphenicol; Erythromycin and the macrolides; possibly Telithromycin and the ketolides
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Which antibiotic inhibits formation of the initiation complex
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Linexolid (Zyvox), an oxaxolidinone
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Why are antibiotics that inhibit either peptidyl transfer or translocation also inhibitors of the puromycin reaction
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Puromycin inhibits translation by causing premature termination. It does this by binding to the A site in place of tyrosyl-tRNA during transpeptidation. The listed antibiotics also cause premature termination
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