Vancomycin Flashcards
Be able to compare and contrast the mechanism of action of vancomycin with that of penicillin.
a) Vancomycin is an inhibitor of gram-(+) cell wall biosynthesis. MOA: binding to the peptidyl side chain D-ala-D-ala terminus in the peptidoglycan precursor (before cross-linking). The transpeptidase reaction that is required for cross-linking is inhibited by the high affinity binding of vancomycin to the substrate. This is similar to the beta-lactam antibiotics in terms of the reaction that is inhibited, but the mechanisms of inhibition are different. Vancomycin also inhibits the transglycosylation step in peptidoglycan synthesis. Penicillin targets PBPs, binding to the transpeptidase enzyme and inhibits the formation of cross-links between peptidoglycan strands.
b) Both inhibit cell wall synthesis.
Be able to state the antibiotic spectrum of vancomycin.
a) Primarily bactericidal and is active against gram-(+) bacteria. All gram-(-) bacteria are not susceptible to vancomycin (very large, too big to get through porin).
Be able to describe the mechanism of bacterial resistance to vancomycin.
a) Mechanism of resistance appears to be mutation of the peptidoglycan cell wall precursor from D-Ala-D-Ala to D-Ala-D-lactate. Vancomycin does not inhibit the transpeptidase when the substrate is D-Ala-D-lactate because vancomycin has 1000 times less affinity for the D-Ala-D-lactate precursor.
Be able to specify the route of administration of vancomycin.
IV
Be able to describe the main therapeutic uses of vancomycin.
a) Clostridium difficile pseudomembranous colitis (relapse or unresponsive to metronidazole treatment).
b) Methicillin-resistant staphylococcus aureus (MRSA)
Be able to describe the main toxic effects of vancomycin.
a) Hypersensitive response red skin rash and potential anaphylaxis
b) Nephrotoxicity and ototoxicity associated with high concentrations of the drug.
Be able to characterize the pharmacokinetics of vancomycin.
a) Highly distributed and 90% eliminated by glomerular filtration.
