Lec 3 Beta Lactams/Cephalosporins Cushman

Question 1

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

Answer 1

cell wall
periplasmic space
larger

Question 2

how many membranes are in gram positive bacteria?

Answer 2

1

Question 3

how many membranes are in gram negative bacteria?

Answer 3

2

Question 4

in gram negative bacteria, the peptidoglycan contains a ____ residue, but in gram positive that residue is replaced by ______

Answer 4

DAP
L-lysine

Question 5

DAP of gram neg and L-lysine of gram pos is crosslinked with what amino acid?

Answer 5

D-Ala

Question 6

the cross-link bridge varies from species to species, but typically consists of about ___ amino acids

Answer 6

5 (ex. staph aureus has bridge of 5 glycine residues)

Question 7

which AA residue do transpeptidases use to catalyze cross-linking?

Answer 7

serine

Question 8

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

Answer 8

serine
four
D-Ala-D-Ala

Question 9

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

Answer 9

hydrolysis

Question 10

~___-___ % of US population is allergic to beta-lactam antibiotics

Answer 10

~6-8%

Question 11

the allergenicity of beta-lactam antibiotics results from the drug acting as a _____, acylating host cell proteins which raises antibodies

Answer 11

hapten

Question 12

two tests for beta-lactam allergy

Answer 12

topical flare and wheal tests

Question 13

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

Answer 13

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)

Question 14

why is penicillin V more stable to hydrolysis in the stomach than penicillin G?

Answer 14

bc electroneg of the ether oxygen dec nucleophilicity of amide carbonyl

Question 15

T or F: penicillins with more lipophilic side chains are more highly protein bound

Answer 15

T (this reduces bioavailability)

Question 16

T or F: heavy metal ions catalyze penicillin degradation rxns and should therefore be kept away from penicillin solutions

Answer 16

T

Question 17

T or F: penicillins are only renally excreted

Answer 17

F (renally or biliary)

Question 18

for penicillins that are excreted by kidneys, ~10% is by _______ ______ and 90% is by _______ _______

Answer 18

glomerular filtration; tubular secretion

Question 19

penicillins are anionic, so adminstering with which drug will cause an increase in half-life?

Answer 19

probenecid

Question 20

T or F: penicillin G should be used with caution in those with asthma

Answer 20

T

Question 21

are penicillin G and V beta-lactamase sensitive or resistant?

Answer 21

sensitive

Question 22

penicillin G and V target gram _______ cocci

Answer 22

positive

Question 23

main diff between penicillins G and V

Answer 23

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)

Question 24

why is methicillin not beta-lactamase sensitive?

Answer 24

steric hindrance of nucleophilic attack

Question 25

MRSA: -due to mutation in __________ (PBP) -the gene encoding for this protein is _____ -the PBP that it codes for is called _____

Answer 25

transpeptidase mecA PBP2A

Question 26

is nafcillin sensitive to beta lactamase?

Answer 26

no

Question 27

which of the following beta-lactamase resistant oral penicillins is still available for oral use? a. oxacillin b. cloxacillin c. dicloxacillin

Answer 27

c. dicloxacillin

Question 28

T or F: oxacillin for injection is no longer available

Answer 28

F

Question 29

two beta-lactamase sensitive broad-spectrum oral penicillins

Answer 29

ampicillin amoxicillin

Question 30

which has better oral absorption, amoxicillin or ampicillin?

Answer 30

amoxicillin

Question 31

antimicrobial spectrum for ampicillin

Answer 31

many gram neg organisms, including salmonella, shegella, proteus mirabilis, E. coli, many strains of haemophilis influenzae and neisseria gonorroeae

Question 32

beta lactamase inhibitors MOA

Answer 32

They acylate the serine hydroxyl group in the active site of the b-lactamase

Question 33

amoxicillin + potassium clavulanate a. augmentin b. unasyn c. zosyn d. avycaz

Answer 33

a. augmentin

Question 34

ampicillin + sulbactam a. augmentin b. unasyn c. zosyn d. avycaz

Answer 34

b. unasyn

Question 35

piperacillin + tazobactam a. augmentin b. unasyn c. zosyn d. avycaz

Answer 35

c. zosyn

Question 36

ceftazidime + avibactam a. augmentin b. unasyn c. zosyn d. avycaz

Answer 36

d. avycaz

Question 37

piperacillin is known as an acylureidopenicillin because it incorporates a _____ moiety

Answer 37

urea

Question 38

why does piperacillin have enhanced potency compared to ampicillin?

Answer 38

added side chain fragment resembles a longer section of the peptidoglycan chain than ampicillin does

Question 39

cephalosporins have a ___ membered ring instead of a ___ membered ring in penicillins

Answer 39

6; 5

Question 40

In contrast to parenteral cephalosporins, the orally active cephalosporins have substituents at ___ that are not chemically reactive. a. C-2 b. C-3 c. C-4 d. C-8

Answer 40

b. C-3

Question 41

cephalexin is an orally active _____ gen cephalosporin a. first b. second c. third d. fourth e. fifth

Answer 41

a. first

Question 42

first gen cephalosporins are primarily active against what bacteria? (4 ones listed)

Answer 42

-gram positive cocci (staph aureus and pyogenes) -group B streptococci (streptococcus agalactiae) -streptococcus pneumoniae

Question 43

cefuroxime is a _____ gen cephalosporin a. first b. second c. third d. fourth e. fifth

Answer 43

b. second

Question 44

The _______ side chain of cefuroxime is less reactive toward enzymatic hydrolysis. This makes it less susceptible to nucleophilic attack. The carbamate is also not a good leaving group, which enhances oral bioavailability in this case

Answer 44

carbamate

Question 45

second gen cephalosporins such as cefuroxime should be protected from light due to what moiety?

Answer 45

oxime ether (syn isomer methoximino can be photochemically isomerized)

Question 46

Third gen cephalosporins are less active against ________ than the first gen agents, but they are much more active vs. Gram _______ bacteria than either the first or second gen agents

Answer 46

staphylcocci; negative

Question 47

T or F: third gen cephalosporins are frequently useful against nosocomial (hospital-acquired) multidrug-resistant strains

Answer 47

T

Question 48

ceftazidime is a _____ gen cephalosporin a. first b. second c. third d. fourth e. fifth

Answer 48

c. third

Question 49

ceftazidime leaving group

Answer 49

charged pyridinium ring at C-3

Question 50

ceftazidime: 1. large _____ _____ moiety at C-7 2. charged _______ _______ ring at C-3 is very good leaving group, makes it parenterally active 3. the side chain ______ confers activity vs gram neg

Answer 50

oxime ether pyridinium ring carboxyl

Question 51

why is cefixime orally active and ceftazidime is not?

Answer 51

cefixime does not have a LG at C-3, the presence of an unreactive substituent at C-3 inc oral bioavailability

Question 52

Fourth gen cephalosporins: They retain the antibacterial spectrum of the third gen cephalosporins and also add ________ ________ and some enterobacteria that are resistant to third gen cephalosporins

Answer 52

pseudomonas aeruginosa

Question 53

cefepime is a ____ gen cephalosporin a. first b. second c. third d. fourth e. fifth

Answer 53

d. fourth

Question 54

cefepime: 1) The syn ________ group at C-7 stabilizes cefepime against b-lactamase. 2) The __________ moiety is a good leaving group and therefore increases the reactivity of the b-lactam and makes it parenterally active (too reactive for oral use).

Answer 54

methoximino N-methylpyrrolidine

Question 55

is cefepime orally or parenterally active?

Answer 55

parenterally

Question 56

ceftaroline is a ____ gen cephalosporin a. first b. second c. third d. fourth e. fifth

Answer 56

e. fifth

Question 57

T or F: ceftaroline fosamil is a prodrug

Answer 57

T

Question 58

T or F: unlike most beta-lactams, ceftaroline is able to inhibit the MRSA PBP2a

Answer 58

T

Question 59

Cephalosporins that have a positively charged _____ on the side chain are more likely to be active against Gram ____ bacteria because they are better able to penetrate the porins in the outer mem

Answer 59

nitrogen; negative

Question 60

T or F: ceftaroline is hydrolyzed by beta lactamases

Answer 60

F (resistant)