Cell wall synthesis inhibitors

Question 1

What is the major group of cell wall synthesis inhibitors?

Answer 1

Beta Lactams

Question 2

What molecular feature distinguishes beta lactams?

Answer 2

Beta lactam ring (site of action and resistance)

Question 3

What was the first beta lactam discovered?

Answer 3

Penicillin

Question 4

What is the mechanism of action of beta lactam drugs?

Answer 4

• Inhibits peptidoglycan
  synthesis
• b-lactam agents bind to the
  transpeptidase and inhibit cell
  wall synthesis
• Disrupts bacterial cell wall
  integrity and causes lysis

Question 5

What is the name of the molecule that Beta Lactams bind to?

Answer 5

Penicillin binding protein (PBP), the transpeptidase

Question 6

What is a mechanism of resistance to penicillin that bacteria can acquire from other bacteria?

Answer 6

Bacteria acquire new PBP from other bacteria that are
resistant to b-lactams

Question 7

What are some drug penetration mechanisms of resistance?

Answer 7

Inability to penetrate to site of action
* Gram (–) outer membrane tough to penetrate
* Gram (-) outer membrane modified with impenetrable porins–no longer permeable
* Can’t handle pus, acidic pH

Question 8

What is the biggest mechanism of resistance to beta-lactam drugs?

Answer 8

b-lactamase enzymes present in bacteria that
target the active site of the drug

Question 9

What group of penicillin derivatives can traverse the outer membrane of gram negatives? What are 2 drawbacks of use of these drugs?

Answer 9

• Aminopenicillins (ampicillin and amoxicillin) have added amino groups to get through the porins of the outer membrane in gram negative bacteria
• These drugs are vulnerable to beta-lactamases so are combined with beta-lactamase inhibitors like clavulenic acid (+ amoxicillin = clavamox)
• Oral administration will kill hindgut fermenters

Question 10

What drug group is less vulnerable to beta lactamase?

Answer 10

Methicillin (antistaphylococcal penicilin) is chemically modified to be less vulnerable to beta-lactamases

Question 11

How does clavulenic acid work?

Answer 11

it is a b-lactamase inhibitor, it binds the
b-lactamase enzyme

Question 12

What is the spectrum of activity of Penicillin?

Answer 12

• Most Gram (+) aerobes
• Most Gram (+) anaerobes
• Little activity against Staph aureus sp.
• Gram (-) are typically resistant

Question 13

What are the most important side effects of Penicillin?

Answer 13

Penicillin hypersensitivity: true for all penicillin
classes!!!
* In order of decreasing frequency: urticaria, fever,
bronchospasm, vasculitis, serum sickness, exfoliative
dermatitis, anaphylaxis
* Can occur without any prior exposure
* Reactions after IM injection of Procaine

Question 14

What are the 4 types of penicillin derivatives and examples?

(5 total)

Answer 14

• Anti-staph penicillins: Methicillin
• Aminopenicillins: Amoxicillin, ampicillin
• Anti-pseudomonas penicillin
• Potentiated penicillin: Clavamox = Amoxicillin + Clavulenic acid

Question 15

What is therapy goal with use of Antistaphylococcal penicillins and what is an example drug?

Answer 15

Methicillin
Goal is treatment of penicillin-resistant bacteria because they are not as vulnerable to b-lactamases

Question 16

What is therapeutic goal of treatment with Aminopenicillins and what are 2 example drugs?

Answer 16

Amoxicillin and Ampicillin
Goal is to treat gram negatives because spectrum of Activity:
* Extended spectrum to include some Gram (-)
-E. coli
-Proteus mirabilis
-Salmonella
* Improved ability to penetrate the outer membrane
of Gram (-) bacteria
* Susceptible to b-lactamases

Question 17

What is the most important adverse effect of Aminopenicillins?

Answer 17

Oral administration will KILL HINDGUT FERMENTERS (horses, guinea pigs, rabbits, hamsters, gerbils)

Question 18

What is therapeutic goal of treatment with Antipseudomonal penicillins?

Answer 18

Spectrum of Activity extended to include Gram (-)
* Pseudomonas aeruginosa
* Enterobacter
* Proteus

Question 19

How are antipseudomonal penicillins given?

Answer 19

Not good orally, typically given parenterally

Question 20

What is therapeutic goal of potentiated penicillins and an example drug?

Answer 20

Potentiated penicillin: Clavamox = Amoxicillin + Clavulenic acid
Penicillins mixed with b-lactamase inhibitors
Spectrum of activity
* Staphylococci sp.
* Bacterioides
* E. coli

Question 21

What is the mechanism of action of cephalosporins?

Answer 21

Inhibits peptidoglycan
synthesis, same as penicillins

Question 22

What type of penicillin would you use to treat enterobacter, proteus, and pseudomonas? How would you give them?

Answer 22

Antipseudomonal Penicillins
Not good orally, typically given parenterally

Question 23

What is the difference between first, second, third, and fourth generation cephalosporins?

Answer 23

First generation: mostly Gram (+), modest Gram (-)
Second generation: added Gram (-)
Third generation: less Gram (+), more Gram (-)
Fourth generation: extended spectrum from 3rd
generation

Question 24

What type of drug and generation is Ceftiofur?

Answer 24

3rd generation cephalosporin

Question 25

What are most important side effects of cephalosporins in general? Of Ceftiofur?

Answer 25

In general, very safe drugs, hypersensitivity, most common, similar to penicillins Antimicrobial induced colitis from Ceftiofur * Younger horses, high stress (racehorses), given IV fast instead of IM

Question 26

Which cephalosporin can you use IM?

Answer 26

Ceftiofur

Question 27

Which generation of cephalosporins is most resistant to beta-lactamases?

Answer 27

Fourth generation

Question 28

What generation of cepahlosporin would you use to treat an infection with a gram positive organism?

Answer 28

First generation

Question 29

Do cephalosporins need to be metabolized to be active?

Answer 29

Little metabolism... EXCEPTION! 3rd generation Ceftiofur requires metabolization to active metabolite for antimicrobial activity (desfuroylceftiofur)

Question 30

What is mechanism of action of carbapenems?

Answer 30

Disrupts bacterial cell wall synthesis by binding penicillin binding proteins; resistant to most b lactamases

Question 31

What are the three subclasses of beta-lactam drugs?

Answer 31

Penicillins and derivatives Cephalosporins Carbapenems

Question 32

What is the therapeutic use of carbapenems?

Answer 32

Most powerful bactericidal activity of the b-lactams Big gun, use as last resort

Question 33

What are the most important side effects of carbapenems?

Answer 33

Extensive metabolism by renal tubules to potentially toxic compound

Question 34

What are the non-beta lactam cell wall synthesis inhibitor drugs?

Answer 34

Bacitracin Vancomycin Teixobactin

Question 35

When would you use bacitracin? Why?

Answer 35

Only used topically: ophthalmic and dermatologic ointments VERY NEPHROTOXIC if given parenterally

Question 36

What is the most important thing to know about vancomycin?

Answer 36

NO VETERINARY FORMULATIONS APPROVED—BIG GUN!

Question 37

What is the method of action of Teixobactin? Spectrum of activity?

Answer 37

Works on 3 different sites to disrupt cell wall synthesis – Binds Lipid II—precursor for peptidoglycan component of cell wall (same site of action for Vancomycin) – Binds Lipid III—precursor for wall teichoic acid (WTA), building block of cell wall – Blocks precursor recycling—leads to depletion of cell wall components Spectrum of activity – Gram(+)—attacks sugar molecules in cell wall – Gram(-)—resistant due to outer membrane

Question 38

Which generation of cephalosporins is most resistant to beta-lactamases?

Answer 38

Fourth generation