ceph 1 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
Why was early interest in cephalosporin low?
Its antibacterial activity was inferior to that of penicillin
What promotes the semi-synthetics of cephalosporin of medicinal value?
Ease of removal of the a-aminoadipoyl side chain to produce 7-aminocephalosporanic acid (7-ACA)
How active is Cephalosporin C compared to benzylpenicillin?
1/1000 as active
What is a notable resistance characteristic 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 beta-lactamases
- Better activity ratio vs Gram-negative and Gram-positive bacteria
What is the significance of the bicyclic ring system in cephalosporins?
Increases ring strain
What is the core structure of Cephalosporin C?
7-Aminocephalosporanic acid (7-ACA)
What is the nomenclature for the fused ring system of cephalosporins?
S-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
What type of modifications improve the properties 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 a key feature of the 7-acylamino side chain in cephalosporins?
Allows for variation in structure-activity relationships (SARs)
What is the mechanism of action of cephalosporins?
Inhibition of bacterial cell wall synthesis
What are first generation cephalosporins known for?
- More active than penicillin G vs some Gram-negative bacteria
- Less likely to cause allergic reactions
- Useful vs penicillinase producing strains of S. aureus
- Not active vs Pseudomonas aeruginosa
- Poorly absorbed from GIT
- Administered by injection
What modification strategy is used for the first generation cephalosporins?
Replace the acetoxy group with a metabolically stable leaving group
What is a common characteristic of first generation cephalosporins regarding absorption?
Poorly absorbed through the gut wall
What is a notable feature of the pyridine ring in first generation cephalosporins?
Stable to metabolism and a good leaving group
What is the activity of first generation cephalosporins against Gram-positive cocci?
Generally lower activity than comparable penicillins but better range of activity
What is the effect of the 3-methyl group in first generation cephalosporins?
Poor leaving group but aids oral absorption
What has been observed regarding resistance in bacteria to first generation cephalosporins?
Resistance has appeared among Gram-negative bacteria due to more effective beta-lactamases
