Term
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Definition
| antimicrobial activity of macrolides |
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Term
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erythromycin A
aglycone = erythronolide A
2 monosaccharides
INACTIVATED BY ACIDS
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prodrugs (esters) |
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Definition
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Term
specific binding to the 50s subunit of ribosome
does not bind to the 80s mammalian subunit = selective toxicity
REVERSIBLE binding to a high-affinity state
macrolides prevent the continuation of protein synthesis
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binding site: at the entrance of the tunnel - they sterically block the progression of the nascent peptide, they also cause premature detachment of incomplete polypeptide chains.
they exclusively bind to the 23s rRNA segment at the peptidyltransferase center |
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Definition
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Term
target site modification: methylation of the 23s rRNA
constitutive resistance - methylating enzyme produced constitutively
inducible resistance - enzyme induction is effected by exposure
active efflux
enzymatic inactivation:
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Definition
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Term
inactivated by acids
absorption: variable absorption, better on an empty stomach; azithromycin, clarithromycin, and dirithromycin are acid stable; erythromycin administered as a prodrug to overcome degradation; prodrug esters are less affected by presence of food; clarithromycin is the best absorbed macrolide
metabolism: only 5-10% is excreted unchanged, metabolism is unclear
distribution: clarithromycin is concentrated in the tissues, erythromycin is very well distributed
elimination: predominantly excreted via hepatic |
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Definition
| pharmacokinetics of macrolides |
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Term
pharmacodynamic: additional binding sites, active against macrolide resistant strains
pharmacokinetic: metabolized to inactive metabolites, well distributed, eliminated in feces and urine |
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Definition
pharmacodynamic and pharmacokinetic properties of talithromycin (ketolide)
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