Cephalosporins

Question 1

What class of antibiotics are cephalosporins?

Answer 1

Beta-lactam antibiotics

Question 2

What is the activity spectrum of cephalosporins?

Answer 2

Broad spectrum with high potency against gram negative organisms.

Question 3

What is the precursor molecule for cephalosporins used in human?

Answer 3

Cephalosporin C

Question 4

What advantage do cephalosporins have over penicillins?

Answer 4

Cephalosporins are beta lactamase resistant.

Question 5

How are the different generations of cephalosporins obtained?

Answer 5

From successive modifications of the cephem ring structure.

Question 6

Cephalosporin C is more active than penicilling G. True or false?

Answer 6

False.

Cephalosporin C is 1/1000 times as active as penicillin G.

Question 7

Cephalosporin C is more stable to acid hydrolysis than penicillin G. True or false?

Answer 7

True

Question 8

Cephalosporin C is more stable to beta-lactamase than oxacillin. True or false?

Answer 8

False.

It is more stable than penicillin G but equivalent to oxacillin.

Question 9

What is 7-aminocephalosporanic acid?

Answer 9

7-ACA is obtained from the cleavage of the aminoadipyl side chain of cephalosporin C. It is most ideally suitable for the synthesis of synthetic analogues.

Question 10

How are synthetic analogues produced from 7-ACA?

Answer 10

By acylation of the C7 amino functional moiety.

Question 11

All cephalosporins consist of a fused bicyclic system. True or false?

Answer 11

True.

Cephalosporins consist of a fused beta-lactam and dihydrothiazine two-ring system and vary in their side chain substituents at C3 and C7.

Question 12

How many generations of cephalosporins are there?

Answer 12

5

Question 13

What is unique about the activity of first generation cephalosporins?

Answer 13

They are active against Staph. and some enteric Gram-negative baccili.
They are hydrolysed by beta-lactamase
They have the lowest activity

Question 14

What is unique about the activity of second-generation cephalosporins?

Answer 14

They are more active against Gram-negative bacteria; some are active against H. influenzae and anaerobes

Question 15

What is unique about the activity of third-generation cephalosporins?

Answer 15

They have the best Gram-negative spectrum;
β-lactamase resistant;
poor activity against staphylococcus

Question 16

What is unique about the activity of fourth-generation cephalosporins?

Answer 16

They have greater activity against gram negative bacteria than the earlier generations due to dipolar ionic zwitterion.

Question 17

What is unique about the activity of fifth-generation cephalosporins?

Answer 17

They are effective against MRSA.

Question 18

Give examples of first generation cephalosporins.

Answer 18

Cephalexin, cephradine, cefazolin, cefadroxil

Question 19

Give examples of second-generation cephalosporins.

Answer 19

Cefuroxime, Cefaclor, Loracarbef, Cefotiam

Question 20

Give examples of third-generation cephalosporins.

Answer 20

Cefixime, cefdinir, ceftibuten, ceftazidime

Question 21

Give examples of fourth-generation cephalosporins.

Answer 21

Cefclidine, Cefepime, Cefpirome

Question 22

Give examples of fifth-generation cephalosporins.

Answer 22

Ceftaroline, ceftobiprole

Question 23

SAR of 1st generation

Answer 23

• Methyl group at C3: acid stable; metabolically stable; orally bioavailable
• α-amino group at C7: optimum activity against Gram-positive bacteria
• Phenyl group at C7: some Gram-negative activity; some β-lactamase stability
• Thiothiadiazole at C3 (cefazolin): greater penicillin protein binding; metabolically stable; longer halflife; not orally active

Question 24

SAR of second generation

Answer 24

• α-iminomethoxy group at C7 (cefuroxime): increased β-lactamase stability due to stereochemical blocking of β-lactam ring
• aminothiazole ring at C7 (cefotiam): increased PBP affinity; increased antimicrobial activity
• Carbacephem ring (Loracarbef): greater chemical stability; potent antibacterial activity
• Cl atom at C3 (Cefaclor): oral bioavailability; shorter half life

Question 25

SAR of third generation

Answer 25

* aminothiazole group at C7: increased β-lactamase resistance * iminomethoxy, iminohydroxy, iminocarboxy groups at C7: increased β-lactamase resistance; increased Gram-negative activity * 7-α-ethylidene group (ceftibuten): increased β-lactamase resistance; broader spectrum * Vinyl group at C3 (Cefdinir and cefixime): oral bioavailability

Question 26

SAR of fourth generation

Answer 26

* Positively charged quaternary nitrogen at C3: easy diffusion through Gram-negative membranes * Iminomethoxy aminothiazole at C7: increased β-lactamase resistance * Aminothiadiazole at C7 (Cefclidine): increased β-lactamase resistance; good PBP binding

Question 27

SAR of fifth generation

Answer 27

* Iminohydroxy aminothiaidazole at C7: resistance to β-lactamase from S. aureus

Question 28

What is the SAR of the cephem ring structure?

Answer 28

* The double bond at C2 is important for activity * The carboxyl group at C2 enables formation of salts and esters which facilitate oral administration * Hydrogen atom at C6 is important for antibacterial activity * Replacement of S with SO2: increases antibacterial activity * Replacement of S with O: increases β-lactamase resistance; may increase activity * Replacement of S with C: increases chemical stability; increases antibacterial activity

Question 29

The only two drugs in the 5th generation are ceftobiprole and ceftaroline. True or false?

Answer 29

True

Question 30

Ceftobiprole has better water solubility than generation 4. True or false?

Answer 30

False. Ceftobiprole has poor water solubility and is administered IV as an ester prodrug called Ceftobiprole medocaril.

Question 31

What compound was ceftaroline developed from?

Answer 31

4th generation cefozopran

Question 32

Ceftaroline is administered in its active form. True or false?

Answer 32

False. Ceftaroline is administered IV as Ceftaroline fosamil, which is dephosphorylated into active Ceftaroline in plasma.

Question 33

What is the designated naming of the fused ring system?

Answer 33

5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid