Exam 1-Cushman Lec 1- Cephalosporins Flashcards
What is the moa of cephalosporins?
Same as penicillins
-reaction with transpeptidases results in inhibition of peptidoglycan cross-linking
How does resistance occur against cephalosporins?
Like penicillins, they are hydrolyzed by B-lactams
How do cephalosporins relate to penicillins regarding allergenicity?
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
How are cephalosporins classified?
1st generation
2nd generation
3rd generation
4th generation
5th generation
What is the trend going from the 1st generation to 3rd generation cephalosporins regarding what bugs they are affective against?
Trend is enhanced Gram - efficacy as you get to higher classes and a loss of Gram + efficacy
First generation cephalosporins are primarily active against which bugs?
Gram + cocci
What are the first generation cephalosporins?
Cefazolin
Cephalexin
What part of their structure gives 1st generation cephalosporins oral activity?
Unreactive side chains at C-3
(such as the CH3 in cephalexin)
Second generation cephalosporins have activity against which bugs?
Gram +
*Also has some Gram - effects
What are the second generation cephalosporins?
Cefuroxime
What structural features are present in 2nd generation cephalosporins?
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
How is cefuroxime given?
po
What is the function of the oxime ether (methoximino) moiety?
Conveys resistance to hydrolysis by most B-lactamases
How do the syn and anti methoximino moieties differ?
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
Like other oxime ether antibiotics, the methoximinos should be protected from what?
light
What bugs do third generation cephalosporins have affects against?
Less active against staphylococci
Much more active toward Gram - bacteria
Almost all of the 3rd generation cephalosporins have what two parts to their structure?
Aminothiazole
Oxime ether at 7-position
What drugs are 3rd generation cephalosporins?
Ceftazidime
Cefixime
What is the function of the large oxime ether moiety at C-7 in ceftazidine?
Conveys enhanced stability vs B-lactamases
What is the function of the charged pyridinium ring at C-3 in ceftazidime?
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
Why is cefixime orally active?
The presence of an unreactive substituent at C-3 increases oral bioavailability
What bugs do fourth-generation cephalosporins target?
Retain the antibacterial spectrum of 3rd generation but add Pseudomonas aeruginosa and some enterobacteria
-Also more active against Gram +
What drug is a third generation cephalosporin?
Cefepime
What is the function of the syn methoximino group at C-7 in cefepime?
Stabilizes cefepime against B-lactamase
What drug is a fifth generation cephalosporin?
Ceftaroline
What is the primary use of ceftaroline?
To treat MRSA
