b-lactam antibiotics

Question 1

b-lactam MOA

Answer 1

inhibit transpeptidases that glue peptidoglycan strands together (inhibits peptidoglycan cross-linking) = defective bacterial cell wall

Question 2

what endogenous molecule do b lactams replicate

Answer 2

the D-Ala-D-Ala fragment of a peptidoglycan molecule

Question 3

what do b-lactamases do?

Answer 3

catalyze b-lactam hydrolysis (open ring and inactivate)

Question 4

which is more stable?

Answer 4

Penicillin V; electronegative oxygen decreases nucleophilicity and stabilizes molecule against hydrolysis

Question 5

penicillin parenteral solution stability

Answer 5

• use parenteral solutions promptly…. Store in the fridge between pH 6-8
• Heavy metal ions catalyze degradation…. keep away from solutions

Question 6

lipophilicity

Answer 6

• more lipophilic = more protein bound (reduces bioavailability and effective conc of free drug)

Question 7

elimination of penicillins

Answer 7

renal and biliary

Question 8

what drug increases the half life of penicillin when co-administered and why

Answer 8

probenecid (both anionic; compete for tubular secretion in kidneys)

Question 9

what is this

Answer 9

penam

Question 10

what is this

Answer 10

penem

Question 11

what is this

Answer 11

carbapenem

Question 12

what is this

Answer 12

cephem

Question 13

what is this

Answer 13

monobactam

Question 14

name & pearls

Answer 14

Penicillin G
Gram+ cocci, B-lactamase sensitive, parenteral

Question 15

name & pearls

Answer 15

penicillin V
gram + cocci, b-lactamase sensitive, ORAL (more stable in acid)

Question 16

name & pearls

Answer 16

methicillin
B-lactamase resistant due to steric hinderance
unstable in acid; parenteral only
discontinued due to resistance

Question 17

staph aureus methicillin resistance mechanism (MRSA mechanism)

Answer 17

mutation in PBP (transpeptidase) mecA & PBP2A

Question 18

name and pearls

Answer 18

nafcillin
b-lactamase resistant, unstable in acid (parenteral only)
very similar to methicillin

Question 19

what are the b-lactamase resistant oral penicillins?

Answer 19

Oxacillin, Cloxacillin, and dicloxacillin

Question 20

name and pearls

Answer 20

dicloxacillin
orally available, b lactamase resistant

Question 21

name and pearls

Answer 21

ampicillin
targets gram + and - bacteria (the -ellas and e coli)
extra charged amino group allows it to be transported through hydrophilic porins in the gram- cell membrane,
orally available, b lactamase sensitive

Question 22

name and pearls

Answer 22

amoxicillin; ampicillin analog; better oral absorption. can target both gram + and gram - bacteria (broad spectrum), b lactamase sensitive

Question 23

MOA of b-lactamase inhibitors

Answer 23

acylate the serine hydroxyl group in the active site of the B-lactamase

Question 24

What are some examples of combo products with b-lactamase inhibitors?

Answer 24

Augmentin, Unasyn, Zosyn (active ingredients are sulbactam, tazobactam, etc)

Question 25

name and pearls?

Answer 25

pipericillin, activity against gram + and gram -, B-lactamase sensitive, broad spectrum, parenteral only.

Question 26

cephalosporin MOA

Answer 26

reaction with transpeptidases (PBPs) results in inhibition of peptidoglycan cross-linking

Question 27

cephalosporin resistance MOA

Answer 27

hydrolyzed by b-lactamases

Question 28

cephalosporin trends from first generation to 3rd generation

Answer 28

enhanced gram - activity and loss of efficacy for gram + bacteria in each generation

Question 29

first gen cephalosporin activity

Answer 29

gram + cocci (staph aureus and pyogenes), group B strep, and strep pneumoniae

Question 30

name and pearls?

Answer 30

mostly gram + cocci, first gen cephalosporin, parenteral only

Question 31

name and pearls?

Answer 31

group at c3 (methyl) not chemically reactive = oral bioavailability, still first gen (mostly gram + activity)

Question 32

second gen cephalosporin activity

Answer 32

gram + and some gram -

Question 33

name and pearls?

Answer 33

cefuroxime second gen cephalosporin, active both parenterally and orally

Question 34

third gen cephalosporins

Answer 34

less active against staph, more active vs gram negative bacteria

Question 35

name and pearls?

Answer 35

large oxime ether at c7 provides stability against b lactamases, too reactive for oral use, active against gram -

Question 36

name and pearls?

Answer 36

cefixime; no leaving group at c3 = orally active, resistant to b-lactamases, active against gram -

Question 37

4th gen cephalosporins

Answer 37

more active against gram +, active against gram - including pseudomonas

Question 38

name and pearls

Answer 38

cefepime, 4th gen cephalosporin, stable against b-lactamase, parenteral only (good leaving group at C3)

Question 39

what is the fifth gen cephalosporin?

Answer 39

ceftaroline fosamil

Question 40

name and pearl?

Answer 40

ceftaroline; prodrug, broad spectrum against MRSA (even PBP2a)

Question 41

How to tell if a cephalosporin will have gram - activity?

Answer 41

positively charged nitrogens on the side chain can better penetrate the porins in the outer membrane of gram - bacteria.