Week 3 Prunuske - Principles of Chemotherapy

Question 1

What do all beta-lactam antibiotics bind to?

Answer 1

Penicillin Binding Proteins (transpeptidases)

Question 2

What kind of reactions do transpeptidases catalyze?

Answer 2

Terminal reactions in bacterial wall synthesis.

(connects the peptidoglycan chains together via peptide bonds)

Question 3

What happens when transpeptidase is inhibited?

Answer 3

cell wall precursors builds up >> activates autolytic enzymes

Question 4

What is the primary mechanism of action of Beta-lactam antibiotics?

Answer 4

• Inhibit cross-linking of the peptidoglycan by transpeptidase
• Weakens cell wall, cell bursts in hypotonic solution
• Bactericidal

Question 5

What are the main two forms of Penicillin?

Answer 5

• Penicillin V (oral)
• Penicillin G (IV form)

(active against Gram +)

Question 6

What is the effect of administering Probenecid simultaneously with Penicillin?

Answer 6

decreases renal excretion >> increases time penicillin is in the blood

(impairs renal secretion of weak acids)

Question 7

Penicillinase cleaves the beta-lactam ring and causes microbial resistance of what drugs?

Answer 7

Penicillins

Question 8

What two drugs are Penicillinase-Resistant Penicillins?

Answer 8

Nafcillin & Dicloxacillin

(very narrow-spectrum, mainly used to treat MSSA)

Question 9

Penicillinase inhibitors (a.k.a. beta-lactamase inhibitors) bind to what and allow penicillin to be an effective?

Answer 9

Bind irreversibly to penicillinase.

(ex. Clavulanate, Sulbactam, and Tazobactam)

Question 10

What class of penicillins are more water soluble and can pass through porin channels?

Answer 10

Aminopenicillins

(wider spectrum, penicillinase-susceptible)

Question 11

What are the two types of Aminopenicillins? Note: both start with “Am”

Answer 11

Ampicillin & Amoxicillin

Question 12

What GI condition is Ampicillin associated with?

Answer 12

pseudomembranous colitis

Question 13

Antipseudomonal penicillins are pretty broad and include what two drugs?

Answer 13

Ticarcillin & Piperacillin

(susceptible to penicillinases)

Question 14

What drug is resistant to penicillinase and is mainly used in the treatment of MSSA?

Answer 14

Nafcillin

Question 15

Which drug is administered if a patient is allergic to penicillin?

Answer 15

Aztreonam

(monocyclic beta-lactams, targets gm-)

Question 16

What is the mechanism of action of Cephalosporins?

Answer 16

inhibit cell wall synthesis by binding to penicillin binding proteins (transpeptidase)

weaken cell wall > autolyse > Bactericidal

Question 17

How are cephalosporins excreted from the body?

Answer 17

The kidney.

Question 18

What is unique about the 3rd generation of cephalosporins compared to the 1st & 2nd generations?

Answer 18

3rd generation can cross the blood brain barrier!

1st & 2nd generations cannot cross the blood brain barrier.

Question 19

What type of prophylaxis are the 1st and 2nd generation cephalosporins used for?

Answer 19

Surgical prophylaxis

Question 20

What cephalosporin drug is used to treat meningitis?

Answer 20

Ceftriaxone

Question 21

What spectrums do cephalosporins have?

Answer 21

1st generation: Gram + cocci

2nd generation: gram - > gram +

3rd generation: gram - (resistant to other Beta-lactams)

4th generation: gram +, gram - including Pseudomonas

5th generation: New (MRSA), resistance to penicillinase

Question 22

What generation of cephalosporins are strongly associated with Clostridium difficile?

Answer 22

3rd generation: Ceftriazone, cefotaxime, ceftazidime, cefdinir

Question 23

What is the mechanism of action of Carbapenems?

Answer 23

contain beta-lactam ring and bind to penicillin binding proteins

Question 24

The spectrum of carbapenems is broad, but what condition is still resistant?

Answer 24

MRSA

Question 25

Carbapenems (Imipenem/cilastatin, meropenem) are administered parenterally, meaning?

Answer 25

IV, IM, SubQ

Question 26

Why is the carbapenem Imipenem administered with cilastatin?

Answer 26

To decrease cleavage of the beta-lactam ring and to prevent the formation of potentially toxic nephrotoxic metabolite.

Question 27

What side effects are associated with carbapenems?

Answer 27

GI distress & cross allergic \*check dose with renal dysfunction to prevent seizures

Question 28

What are some symptoms associated with a penicillin allergy?

Answer 28

nausea, diarrhea, urticaria, angioedema, and anaphylaxis Hypersensitivity (mild rash to anaphylaxis) Seizure if CNS penetration

Question 29

What target of cell wall synthesis does Vancomycin act on?

Answer 29

Transglycosylase - prevents peptidoglycan synthesis (bactericidal)

Question 30

What is the spectrum of Vancomycin?

Answer 30

Very narrow, only gram + MRSA & C.diff oral vancomycin is poorly absorbed

Question 31

What are the four mechanisms of resistance that can result in cross-resistance amongst Beta-lactams?

Answer 31

1. Expression of beta-lactamases (penicillinases, cephalosporinases, amidases) 2. change in the structure of Penicillin Binding Proteins 3. Decrease in uptake of the drug (intrinsically resistant) 4. Upregulation of efflux pumps

Question 32

What are possible side effects of Vancomycin?

Answer 32

Red man syndrome (hypersensitivity due to secretion of histamines) Nephrotoxicity

Question 33

What reaction does Bacitracin prevent in the elongation of the peptidoglycan cell wall?

Answer 33

dephosphorylation of the bactoprenol carrier.

Question 34

What is the side of effect of Bacitracin when give IM?

Answer 34

nephrotoxicity

Question 35

Polymyxin B binds to phosphatidylethanolamine in the membrane leading to what as a result?

Answer 35

Creating holes in the membrane that leads to the release of cellular contents.

Question 36

What is the spectrum of Polymyxin B?

Answer 36

Gram - bacilli effective against multidrug resistant microbes such as Pseudomonas and KBC (Used in combination with other antibiotics to help facilitate entry.)

Question 37

What is the only listed side effect of Polymyxin B?

Answer 37

Nephrotoxicity

Question 38

Aggregation and depolarization of a cell occurs when Daptomycin binds to what part of the cell?

Answer 38

Cell membrane

Question 39

What difficult condition is Daptomycin used to treat?

Answer 39

MRSA + VRSA

Question 40

What types of microorganisms does Daptomycin treat?

Answer 40

Gram + | (MRSA, vanco-resistant)

Question 41

What was the only side effect of Daptomycin listed?

Answer 41

reversible organizing pneumonia binds pulmonary surfactant accumulating in pulmonary spaces