Lec 3 Beta Lactams/Cephalosporins Cushman Flashcards
in Gram-(+) bacteria, b-lactamases are excreted through the _____ _____ to the external environment. In Gram-(–) bacteria, the b-lactamases are confined to the _______ _______. The b-lactamases in Gram-(+) bacteria therefore have to be produced in _______ quantities
cell wall
periplasmic space
larger
how many membranes are in gram positive bacteria?
1
how many membranes are in gram negative bacteria?
2
in gram negative bacteria, the peptidoglycan contains a ____ residue, but in gram positive that residue is replaced by ______
DAP
L-lysine
DAP of gram neg and L-lysine of gram pos is crosslinked with what amino acid?
D-Ala
the cross-link bridge varies from species to species, but typically consists of about ___ amino acids
5 (ex. staph aureus has bridge of 5 glycine residues)
which AA residue do transpeptidases use to catalyze cross-linking?
serine
beta-lactam antibiotic MOA:
1. they acylate the transpeptidase ____ residue in active site, inactivates enzyme and cell wall is subject osmotic stress
2. highly strained ___-membered ring made
3. the structures of the beta-lactams resemble the _________ fragment that is acted on by transpeptidases
serine
four
D-Ala-D-Ala
resistance to beta-lactam antibiotics: induction or elaboration of bacterial beta-lactamases leads to _______ of the acylated beta-lactamase intermed, so the enzyme can hydrolyze many drug molecules rapidly
hydrolysis
~___-___ % of US population is allergic to beta-lactam antibiotics
~6-8%
the allergenicity of beta-lactam antibiotics results from the drug acting as a _____, acylating host cell proteins which raises antibodies
hapten
two tests for beta-lactam allergy
topical flare and wheal tests
which of the following is TRUE about penicillin degradation?
a. penicillin hydrolysis products have antibiotic activity
b. hydrolysis of beta-lactam is reversible
c. electroneg substituents reduce nucleophilicity, which stabilizes the penicillin against hydrolysis under acidic conditions
d. parenteral pencillins should be stored in fridge between pH 5 and 6
c. electroneg substituents reduce nucleophilicity, which stabilizes the penicillin against hydrolysis under acidic conditions
(a is no activity; b is irreversible; d is between pH 6 and 6.8)
why is penicillin V more stable to hydrolysis in the stomach than penicillin G?
bc electroneg of the ether oxygen dec nucleophilicity of amide carbonyl
T or F: penicillins with more lipophilic side chains are more highly protein bound
T (this reduces bioavailability)
T or F: heavy metal ions catalyze penicillin degradation rxns and should therefore be kept away from penicillin solutions
T
T or F: penicillins are only renally excreted
F (renally or biliary)
for penicillins that are excreted by kidneys, ~10% is by _______ ______ and 90% is by _______ _______
glomerular filtration; tubular secretion
penicillins are anionic, so adminstering with which drug will cause an increase in half-life?
probenecid
T or F: penicillin G should be used with caution in those with asthma
T
are penicillin G and V beta-lactamase sensitive or resistant?
sensitive
penicillin G and V target gram _______ cocci
positive
main diff between penicillins G and V
V is more stable in acid due to ether oxygen (meaning it is more stable in the stomach so blood levels are higher when given orally)
why is methicillin not beta-lactamase sensitive?
steric hindrance of nucleophilic attack
