Antibacterial- part 2 mech Flashcards
What is cephalosporins?
- its a fungus
- activity against penicillin resistant bacteria becase apparent resistanct to b-lactamase
what is the difference between cephalosporins and penicillin?
feature a six membered ring fused to the b-lactam and so has
less ring strain (so more stable to acid hydrolysis than the penicillins)
what are some structure activity for Cephalosporin?
- less active than penicillin
- but broader spectrum of activity
- G+ve better than G-ve (G-ve b-lactamases more specific for cephalosporins)
how can metabolic inactivation of cephalosporins occur?
-removing the leaving group can make it it better absorbed but reduce activity as methyl isnt a good leaving group
why is it good to inhibit alanine
racemase and D-alanyl-D-alanyl
synthetase?
in order to prevent D-alanine being produced and consequently forming D-Ala-D-Ala dipeptide which will be part of the cell wall making it very strong and prevent hydrolysis of the cell wall.
what does D-Cycloserine do?
- its a drug to prevent D-Ala-D-Ala dipeptide being made
- micics D-alanine and inhibits both the enzymes
what is Vancomycin?
bind to the substrate rather than enzyme so it cant fit in the active site.
-Inhibits peptidoglycan crosslinking by binding to the
D-Ala-D-Ala terminus of the crosslinking peptide.
what is a vancomycin resistant
-mutation in the biosynthesis of its cell wall
-where the terminal D-alanine that is removed in the
crosslinking reaction has been replaced by lactic acid (ie ester rather than
an amide linkage.
how/why can you get over antibiotic resistance when treating?
- Different antibiotics target different stages of cell wall biosynthesis
- use combination therapies as they target different places so may help
- The next serious challenges are multi-drug resistant bacteria
why was prontosil active in vivo but not in vitro?
-its a prodrug needs to be metabolised
how do sulfonamides work?
-inhibit folic acid biosythesis
-inhibit dihydropteroate synthase
-can be utalised by the eynzme
-Blocking folic acid biosynthesis blocks nucleic acid synthesis,
hence cell growth and division stops.
why is folic acid important?
-for nucleic acid biosythesis
what does sufonamides compete with for the enzyme active site?
PABA
why is Sulfonamides considered as a Bacteriostatic?
Bacteriostatics don’t kill the bacteria but they give the body a
chance to amount an effective immune response to finish the job
why are sulfanmides selective inhibitors of folic acid biosynthesis in bacteria?
Bacteria lack the transport proteins required for folic acid uptake
what is the benefit of using both Sulfamethoxazole and Trimethoprim?
lower chances of resistance of using both
what does changing the thiazole unit to a pyrimidine do to in a sulfathiazole?
- prevents acetylation n the blood and blocking of the kidney tubules
- overall reduces toxicity
what are aminoglycosides?
-Aminoglycosides are bacteriocidal (most other protein synthesis inhibitors are bacteriostatic) -made from aminosugars
how may kanamycin (Aminoglycosides) be inactivated?
by enzyme modification
what are tetracyclines?
The most widely prescribed broad spectrum antibiotics after pencillins
how does bacteria resistance occur through genetic transfer?
- replication of bacteria leading to mutation
- by sharing bacterial information, transfer of plasmid
how does bacteria resistance occur?
Target enzyme mutation
Enzymatic modification/inactivation of the drug
Modified cell membrane structure preventing intracellular drug delivery
what are some solutions for antibiotic resistance?
- Combination therapy
- Complete prescribed drug regimens
- Understand mechanistic intimacies of drug action and anticipate resistance problems.
- Find novel biological targets
- Target proteins whose function is critical for bacteria virulence and/or survival
