Antibacterial- part 2 mech

Question 1

What is cephalosporins?

Answer 1

• its a fungus

- activity against penicillin resistant bacteria becase apparent resistanct to b-lactamase

Question 2

what is the difference between cephalosporins and penicillin?

Answer 2

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)

Question 3

what are some structure activity for Cephalosporin?

Answer 3

• less active than penicillin
• but broader spectrum of activity
• G+ve better than G-ve (G-ve b-lactamases more specific for cephalosporins)

Question 4

how can metabolic inactivation of cephalosporins occur?

Answer 4

-removing the leaving group can make it it better absorbed but reduce activity as methyl isnt a good leaving group

Question 5

why is it good to inhibit alanine
racemase and D-alanyl-D-alanyl
synthetase?

Answer 5

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.

Question 6

what does D-Cycloserine do?

Answer 6

• its a drug to prevent D-Ala-D-Ala dipeptide being made

- micics D-alanine and inhibits both the enzymes

Question 7

what is Vancomycin?

Answer 7

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.

Question 8

what is a vancomycin resistant

Answer 8

-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crosslinking reaction has been replaced by lactic acid (ie ester rather than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.

Question 9

how/why can you get over antibiotic resistance when treating?

Answer 9

• 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

Question 10

why was prontosil active in vivo but not in vitro?

Answer 10

-its a prodrug needs to be metabolised

Question 11

how do sulfonamides work?

Answer 11

-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.

Question 12

why is folic acid important?

Answer 12

-for nucleic acid biosythesis

Question 13

what does sufonamides compete with for the enzyme active site?

Answer 13

PABA

Question 14

why is Sulfonamides considered as a Bacteriostatic?

Answer 14

Bacteriostatics don’t kill the bacteria but they give the body a
chance to amount an effective immune response to finish the job

Question 15

why are sulfanmides selective inhibitors of folic acid biosynthesis in bacteria?

Answer 15

Bacteria lack the transport proteins required for folic acid uptake

Question 16

what is the benefit of using both Sulfamethoxazole and Trimethoprim?

Answer 16

lower chances of resistance of using both

Question 17

what does changing the thiazole unit to a pyrimidine do to in a sulfathiazole?

Answer 17

• prevents acetylation n the blood and blocking of the kidney tubules
• overall reduces toxicity

Question 18

what are aminoglycosides?

Answer 18

-Aminoglycosides are
bacteriocidal (most other
protein synthesis inhibitors
are bacteriostatic)
-made from aminosugars

Question 19

how may kanamycin (Aminoglycosides) be inactivated?

Answer 19

by enzyme modification

Question 20

what are tetracyclines?

Answer 20

The most widely prescribed broad spectrum antibiotics after pencillins

Question 21

how does bacteria resistance occur through genetic transfer?

Answer 21

• replication of bacteria leading to mutation

- by sharing bacterial information, transfer of plasmid

Question 22

how does bacteria resistance occur?

Answer 22

Target enzyme mutation
Enzymatic modification/inactivation of the drug
Modified cell membrane structure preventing intracellular drug delivery

Question 23

what are some solutions for antibiotic resistance?

Answer 23

1. Combination therapy
2. Complete prescribed drug regimens
3. Understand mechanistic intimacies of drug action and anticipate resistance problems.
4. Find novel biological targets
5. Target proteins whose function is critical for bacteria virulence and/or survival