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Drug Mechanisms > Inhibitors of Cell Wall Synthesis > Flashcards

Inhibitors of Cell Wall Synthesis Flashcards

1
Q

Name the inhibitors of cell wall synthesis

A

1) B-Lactams
2) Fosfomycin
3) Cycloserine
4) Bacitracin
5) Vancomycin
6) Dalbavancin
7) Telavancin
8) Oritavancin

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2
Q

What is the antibiotic vancomycin classified as?

A

A glycopeptide

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3
Q

Which antibiotics are classified as lipoglycopeptides?

A

Dalbavancin, Telavancin, and Oritavancin

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4
Q

Are all inhibitors of cell wall synthesis bacteriostatic or bactericidal at the clinical dose?

A

Bactericidal

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5
Q

What is the one stipulation when considering whether or not the inhibitors of cell wall synthesis will be useful to treat an infection?

A

The bacteria have to be replicating

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6
Q

What antibiotics have a beta-lactam ring in their structure?

A

Penicillins, cephalosporins, monobactams, and carbapenems

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7
Q

Which antibiotic inhibits the conversion of NAG to NAM?

A

Fosfomycin

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8
Q

Which enzyme is fosfomycin a structural analog of?

A

Phosphoenolpyruvate

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9
Q

What enzyme does fosfomycin inhibit?

A

enolpyruvate transferase

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10
Q

What class of beta-lactamases has better antimicrobial action?

A

Class 2

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11
Q

Which beta-lactamase inhibitors are class 1?

A

1) Clavulanic acid
2) Avibactam
3) Tazobactam
4) Sulbactam

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12
Q

What beta-lactamases are class 1 inhibitors best at inhibiting?

A

Serine B-lactamases

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13
Q

What can happen to carbapenems when attacked by carbapenemases and metallo-B-lactamases?

A

They can be hydrolyzed which irreversibly inactivates them

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14
Q

Which class 1 inhibitor of beta-lactamases is effective against most extended spectrum B-lactamases and carbapenemases?

A

Avibactam

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15
Q

What is the relationship between B-lactams and class 1 B-lactamase inhibitors?

A

Synergistic

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16
Q

What is the relationship between a B-lactam and a carbapenem?

A

Antagonistic

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17
Q

Why is there an antagonistic relationship between a B-lactam and a class 2 B-lactamase inhibitor?

A

Because carbapenems cause an increase in the release of B-lactamases which destroy the B-lactam antibiotic

18
Q

What are the main mechanisms of resistance to B-lactams in gram-negative bacteria?

A

Active efflux and impaired drug entry

19
Q

What can a bacterial cell modify in order to prevent B-lactams from being productive?

A

Penicillin-binding proteins

20
Q

What are the features of a gram-positive bacteria?

A

They have a thick peptidoglycan cell wall, but they aren’t highly sophisticated

21
Q

What are the features of a gram-negative bacteria?

A

They have a very thin peptidoglycan layer, but they are highly adaptive

22
Q

What do beta-lactams bind to in order to inhibit cell wall synthesis?

A

They bind covalently to penicillin-binding proteins

23
Q

What step do beta-lactams inhibit?

A

Step 5

24
Q

How many domains does the penicillin-binding protein have?

A

2

25
Q

What are the two domains of the penicillin-binding protein?

A

The transpeptidase domain and the glycosyltransferase domain

26
Q

Which domain do beta-lactams inhibit?

A

Only the transpeptidase domain

27
Q

What does the transpeptidase domain do?

A

It cross-links the polypeptide chains to form the rigid peptidoglycan layer

28
Q

What step does cycloserine inhibit?

A

2

29
Q

What steps do vancomycin, dalbavancin, telavancin, and oritavancin inhibit?

A

4 and 5

30
Q

What step does fosfomycin inhibit?

A

1

31
Q

What step does bacitracin inhibit?

A

3

32
Q

How do VERSA strands protect themselves against vancomycin?

A

They add a D-lactate to the end of the D-Ala so that vancomycin can’t bind

33
Q

What can vancomycin bind to in order to kill bacterial cells?

A

They can bind to the terminus of D-Ala-D-Ala and to the pentaglycine bridge

34
Q

What is the result of vancomycin being able to bind to two different binding sites in the bacterial cell?

A

It can inhibit the transpeptidation step and the transglycosylation step

35
Q

How do VISA strands protect themselves against vancomycin?

A

They thicken the cell wall by adding more D-Ala-D-Ala residues that are false targets for vancomycin

36
Q

What do dalbavancin, telavancin, and oritavancin share with vancomycin?

A

a primary mechanism of action

37
Q

What do dalbavancin, telavancin, and oritavancin have that classify them as lipoglycopeptides?

A

A long, lipophilic side chain

38
Q

What does the lipophilic side chain help telavancin do?

A

Depolarize the cell membrane and compromise its function

39
Q

What does the lipophilic side chain help oritavancin do?

A

It dimerizes to strongly anchor itself to the cell membrane improving the ability to bind to targets

40
Q

Studies show that oritavancin can inhibit what?

A

RNA synthesis

41
Q

Why can oritavancin be used in bacterial infections that are resistant to vancomycin?

A

Because it has a higher affinity for D-Ala-D-Lactate

Drug Mechanisms (9 decks)

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