ceph 1+ ceph 2 Flashcards
What are cephalosporins?
Antibacterial agents which inhibit bacterial cell wall synthesis
Discovered from a fungal colony in Sardinian sewer water in 1948
When was Cephalosporin C identified?
1961
How does the potency of Cephalosporin C compare to benzylpenicillin?
Cephalosporin C is 1/1000 as active as benzylpenicillin
What is a significant resistance feature of Cephalosporin C?
Remarkably penicillinase resistant
What are the disadvantages of Cephalosporin C?
- Polar due to the side chain - difficult to isolate and purify
- Low potency - limited to treatment of urinary tract infections
- Not absorbed orally
What are the advantages of Cephalosporin C?
- Nontoxic
- Lower risk of allergic reactions compared to penicillins
- More stable to acid conditions
- More stable to β-lactamases
- Better ratio of activity against Gram-negative and Gram-positive bacteria
What is a major compound derived from Cephalosporin C?
7-aminocephalosporanic acid (7-ACA)
What is the significance of the acetoxy group in cephalosporins?
Acts as a good leaving group and aids the mechanism
What modifications are required for the preparation of semisynthetic cephalosporins?
- Increased acid stability
- Improved pharmacokinetic properties
- Broadened antimicrobial spectrum
- Increased activity against resistant microorganisms
- Decreased allergenicity
- Increased tolerance after parenteral administration
What is the importance of the β-lactam ring in cephalosporins?
Crucial to the mechanism of action
What is the effect of the carboxylic acid at position 4 in cephalosporins?
Important to binding
How are 7-ACA derivatives typically generated?
By chemical hydrolysis
What is the characteristic of first generation cephalosporins?
More active than penicillin G against some Gram-negative bacteria
What is a common administration route for first generation cephalosporins?
Administered by injection
What is a key attribute of the metabolite of first generation cephalosporins?
Gives a free 3-hydroxymethyl group (deacetylation)
What makes the pyridine ring in first generation cephalosporins significant?
Stable to metabolism and a good leaving group
What is the effect of substituting a methyl group at the 3-position in first generation cephalosporins?
Poor leaving group but aids oral absorption
What is the general summary of first generation cephalosporins?
- Generally lower activity than comparable penicillins
- Better range of activity than comparable penicillins
- Best activity against Gram-positive cocci
- Useful against some Gram-negative infections
- Poorly absorbed across the gut wall (except for 3-methyl substituted cephalosporins)
- Most are administered by injection
- Resistance has appeared among Gram-negative bacteria
What is Cepll’lamycijns?
Isolated from a culture of Streptomyces clavuligerus. First 13-lactam to be isolated from a bacterial source. Modifications carried out on the 7-acylamino side chain.
What is Cefoxitin’s chemical structure?
(6 S, 7 R)-3-(carbamoyloxymethyl)-7-methoxy-8-oxo-7-[(2-thiophen-2-ylacetyl}amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
What are the key characteristics of Cefoxitin?
- Broader spectrum of activity than most first generation cephalosporins
- Greater resistance to β-lactamase enzymes
- The 7-methoxy group may act as a steric shield
- The urethane group is stable to metabolism.
What defines second generation cephalosporins?
Includes compounds like Cefuroxime, which have greater stability against some β-lactamases.
