Exam 1-Cushman Lec 1- Cephalosporins

Question 1

What is the moa of cephalosporins?

Answer 1

Same as penicillins
-reaction with transpeptidases results in inhibition of peptidoglycan cross-linking

Question 2

How does resistance occur against cephalosporins?

Answer 2

Like penicillins, they are hydrolyzed by B-lactams

Question 3

How do cephalosporins relate to penicillins regarding allergenicity?

Answer 3

Allergic reactions are less common and less severe with cephalosporins

-but small risk of cross-reactivity between the two classes so use with caution in patients who are allergic to penicillins

Question 4

How are cephalosporins classified?

Answer 4

1st generation
2nd generation
3rd generation
4th generation
5th generation

Question 5

What is the trend going from the 1st generation to 3rd generation cephalosporins regarding what bugs they are affective against?

Answer 5

Trend is enhanced Gram - efficacy as you get to higher classes and a loss of Gram + efficacy

Question 6

First generation cephalosporins are primarily active against which bugs?

Answer 6

Gram + cocci

Question 7

What are the first generation cephalosporins?

Answer 7

Cefazolin
Cephalexin

Question 8

What part of their structure gives 1st generation cephalosporins oral activity?

Answer 8

Unreactive side chains at C-3

(such as the CH3 in cephalexin)

Question 9

Second generation cephalosporins have activity against which bugs?

Answer 9

Gram +
*Also has some Gram - effects

Question 10

What are the second generation cephalosporins?

Answer 10

Cefuroxime

Question 11

What structural features are present in 2nd generation cephalosporins?

Answer 11

Have a carbamate side chain that is less reactive toward enzyme hydrolysis
-due to electron-donating NH2 on the carbamate
-this neutralizes the partial positive charge on the carbonyl and makes it less susceptible to nucleophilic attack
*carbamate is not a good leaving group, enhances oral bioavailability

Question 12

How is cefuroxime given?

Answer 12

po

Question 13

What is the function of the oxime ether (methoximino) moiety?

Answer 13

Conveys resistance to hydrolysis by most B-lactamases

Question 14

How do the syn and anti methoximino moieties differ?

Answer 14

syn is more resistant to enzymatic hydrolysisthan the anti isomer and can be photochemically isomerized to the anti isomer to form a 1:1 mixture of the two

Question 15

Like other oxime ether antibiotics, the methoximinos should be protected from what?

Answer 15

light

Question 16

What bugs do third generation cephalosporins have affects against?

Answer 16

Less active against staphylococci

Much more active toward Gram - bacteria

Question 17

Almost all of the 3rd generation cephalosporins have what two parts to their structure?

Answer 17

Aminothiazole

Oxime ether at 7-position

Question 18

What drugs are 3rd generation cephalosporins?

Answer 18

Ceftazidime
Cefixime

Question 19

What is the function of the large oxime ether moiety at C-7 in ceftazidine?

Answer 19

Conveys enhanced stability vs B-lactamases

Question 20

What is the function of the charged pyridinium ring at C-3 in ceftazidime?

Answer 20

A good leaving group that strongly activates the B-lactam ring

Charged pyridinium ring imparts enhanced aqueous solubility and makes it parenterally active (too reactive for oral use)

*This is why ceftazidime is used parenterally

Question 21

Why is cefixime orally active?

Answer 21

The presence of an unreactive substituent at C-3 increases oral bioavailability

Question 22

What bugs do fourth-generation cephalosporins target?

Answer 22

Retain the antibacterial spectrum of 3rd generation but add Pseudomonas aeruginosa and some enterobacteria

-Also more active against Gram +

Question 23

What drug is a third generation cephalosporin?

Answer 23

Cefepime

Question 24

What is the function of the syn methoximino group at C-7 in cefepime?

Answer 24

Stabilizes cefepime against B-lactamase

Question 25

What drug is a fifth generation cephalosporin?

Answer 25

Ceftaroline

Question 26

What is the primary use of ceftaroline?

Answer 26

To treat MRSA