Antimicrobials: Part 3: MOAs of drugs that work within the cell wall + membrane Flashcards
What is the MOA for penicillinase-sensitive penicillins?
Penicillin binds to transpeptidases (due to how penicillin mimics alanine residues).
Once this interaction occurs, the enzyme is inactivated.
This ultimately blocks cross-linking of the peptidoglycan cell wall.
What are the three components of resistance of penicillinase-sensitive penicillins?
There is resistance to these drugs in the form of modified (mutated) transpeptidases, reduced bacterial penetration, and the beta-lactamase enzyme.
How can penicillinase-sensitive penicillins be further characterized?
Natural penicillins: Penicillin G, V
Aminopenicillins: AmIpicillin and amoxicillin
How do the aminopenicillins differ from the natural penicillins?
Ampicillin and amoxicillin can penetrate the porin channels of gram negative bacteria.
However, these two are just as sensitive as G and V to beta-lactamases.
What is the MOA of penicillinase-resistant penicillins?
Penicillin binds to transpeptidases (due to how penicillin mimics alanine residues).
Once this interaction occurs, the enzyme is inactivated.
This ultimately blocks cross-linking of the peptidoglycan cell wall.
**HOWEVER: there is a bulky R group that blocks penicillinase –> ultimately can resist beta-lactamases
What is a very special characteristic of penicillinase-resistant penicillins?
This group is the only type of penicillin that can resist penicillinase (a type of beta-lactamase).
How is MRSA related to the penicillinase-resistant penicillins?
MRSA has an altered penicillin binding site, so these type of drugs aren’t as effective as others :(
What is the MOA of the antipseudomonals?
Penicillin binds to transpeptidases (due to how penicillin mimics alanine residues).
Once this interaction occurs, the enzyme is inactivated.
This ultimately blocks cross-linking of the peptidoglycan cell wall.
Yep, still sensitive to penicillinase, though.
What makes a drug get the ending “-cillin?”
Their structure has both a thiazoladine ring and a beta lactam ring. That is what makes a penicillin, a penicillin!
What happened when the “-cillin” set of drugs became pretty resistant? What did scientists have to do?
The “-cillin” set of drugs became pretty resistant, so scientists had to manipulate it. What ended up happening was that they removed the thiazoladine ring but kept the beta-lactam ring. This gave us three special groups of drugs called “beta-lactams” (cephalosporins, carbapenems, and monobactams).
What are the MOA of cephalosporins, generations I-V?
Same as the penicillins!
They bind transpeptidases, prevent peptidoglycan crosslinking, and ultimately result in autolysis of the cell.
As the generations of cephalosporin were developed, they became more resistant to…
Beta-lactamases
Which generation of cephalosporins can penetrate the blood brain barrier really well?
3rd generation = most achieve good CNF penetration (aka can cross BBB)
Why is the 5th generation cephalosporin so special in terms of treatment?
2nd question: what do they bind via their unique MOA?
5th generation (ceftaroline) is active against MRSA, VRSA, and E. faecalis!!! Woah daddy!
Remember: Binds to a specific penicillin-binding protein called PBP2a**
What is the MOA of carbapenems?
Same as the penicillins!
They bind transpeptidases, prevent peptidoglycan crosslinking, and ultimately result in autolysis of the cell.
***Note: resistant to cleavage by most beta-lactamases. They are big gun antibiotics.
