B-Lactams Flashcards
What do antibiotics need to be active?
*B lactam ring
*free carboxylic acid in specific stereochemistry (lined bond)
*strained bicyclic ring
*acylamino side chain in specific stereochemistry
What causes variation of penicillin general structure?
Varying R group on acylamino side chain
Effects
*acitvity
*acid stability
*spectrum of activity
*ability to withstand attack from B-lactamase
How do penicillins work?
*binds to transpeptidase enzyme- inhibits cross linking of peptidoglycan layers in bacterial cell wall.
*cell loses structural integrity
*cell can’t resist internal turgor pressure- wall can penetrate and kill cell
What improves the ability of a penicillin to bind to transpeptidase enzyme?
Smaller R group on acylamino chain
What makes a penicillin more acid stable?
R must be electron withdrawing I.e O, N, Cl, F (electronegative)
Acid stable
What makes a penicillin broad spectrum?
An OH or NH directly attached to carbon alpha to carbonyl group (basically start of R group)
Makes it hydrophilic- to pass through channels in outer membrane of G negative bacteria
How does a penicillin resist deactivation by b-lactamases?
Bulky R group- penicillin too bulky to fit into B-lactamase active site
OR
ortho disubstituted phenyl ring with small substituents is perfect size
NOTE- too bulky reduces action against transpeptidase- reduces activity
What else can be administered to help with B lactam resistance?
B-lactamase inhibitors- aren’t antimicrobial themselves but help prevent b lactamase degradation on b lactams
Eg Co- Amoxiclav
What are methods of b-lactam resistance?
*mutations to transpeptidase enzyme so b-lactams can no longer bind
*penicillins pumped out of cell by efflux pump before can exert effects
*degradaded by B-lactamases
*channel proteins in G negative cell wall mutated so penicillin can’t cross over cell membrane
