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PT 1 > L22 Cell Wall Inhibitors I > Flashcards

L22 Cell Wall Inhibitors I Flashcards

1
Q

What are the four major categories of beta-lactams?

A
  1. Penicillins
  2. Cephalosporins
  3. Monobactams
  4. Carbapenems
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2
Q

What is the common chemical structure in all beta-lactams?

A

4-membered ring

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3
Q

What is the mechanism of action of all beta-lactams?

A

Inhibition of cell wall synthesis by binding to and inhibiting penicillin-binding proteins (PBPs) located in the bacterial cell membranes

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4
Q

What are the three major mechanisms of resistance to beta-lactams developed by bacteria?

A
  1. Beta-lactamase enzyme production
  2. PBP alteration
  3. Decreased penetration via alteration of outer membrane porin proteins
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5
Q

Are beta-lactams bactericidal or bacteriostatic? Are they time-dependent or dose-dependent? Are there any exceptions?

A

Bactericidal; time-dependent except against Enterococcus spp.

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6
Q

What is the elimination half-life of beta-lactams and what are the implications of this?

A

<2 hours; frequent dosing (exception to half-life –> procain penicillin G, benzathine penicillin G, some cephalosporins, one carbapenem)

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7
Q

How are beta-lactams eliminated? What are the exceptions?

A

Primarily eliminated unchanged by the kidneys, except nafcillin, oxacillin, ceftriaxone, and cefoperazone

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8
Q

What is cross-allergenicity and is it exhibited by beta-lactams?

A

There is an increased likelihood of allergy to other beta-lactams if there is allergy to one beta-lactam; aztreonam is an exception.

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9
Q

What is the general shared structure of all penicillins?

A

Beta-lactam ring attached to a 5-membered thiazolidine ring

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10
Q

When are PBPs expressed?

A

Only during cell division

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11
Q

What specific step of cell walls synthesis is inhibited by beta-lactams?

A

The final transpeptidation step of peptidoglycan synthesis

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12
Q

Where are PBPs located?

A

Cell membrane

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13
Q

What do beta-lacatamse enzymes do?

A

Hydrolyze the beta-lactam ring, inactivating the antibiotic

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14
Q

What are the gram-positive bacteria that produce beta-lactamase enzymes?

A

Penicillin-resistant S. aureus

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15
Q

What are the gram-negative bacteria that produce beta-lactamase enzymes?

A
  1. H. influenzae
  2. Moraxella catarrhalis
  3. N. gonorrhoeae
  4. E. coli
  5. Klebsiella pneumoniae
  6. Enterobacter spp.
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16
Q

What are the gram-negative anaerobic bacteria that produce beta-lactamase enzymes?

A

Bacteroides fragilis

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17
Q

How does alteration in the structure of PBPs lead to resistance?

A

The alteration leads to decreased binding affinity by the antibiotics

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18
Q

What 2 bacteria alter PBP structure?

A

Methicillin-resistant S. aureus (MRSA) and penicillin-resistant S. pneumoniae (PRSP)

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19
Q

What was the first group of penicillins to be discovered and used clinically?

A

Natural penicillins

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20
Q

From what are natural penicillins derived?

A

Penicillium notatum

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21
Q

What are 4 examples of natural penicillins and how are they administered?

A
  1. Aqueous penicillin G (IV)
  2. Benzathine penicillin G (IM)
  3. Procaine penicillin G (IM)
  4. Penicillin VK (oral)
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22
Q

Which Gram-positive bacteria are susceptible to natural penicillins?

A
  1. Penicillin-susceptible S. aureus
  2. Penicillin-suspectible S. pneumoniae
  3. Group streptococci
  4. Viridans streptococci
  5. Enterococcus spp.
  6. Bacillus spp.
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23
Q

Which Gram-negative bacteria are susceptible to natural penicillins?

A
  1. Neisseria spp.
  2. Pasteurella multocida
  3. Clostridium spp. (anaerobe)
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24
Q

Which other bacteria are susceptible to natural penicillins and what disease do they cause?

A
  1. Treponema pallidum - syphilis
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25
Q

What are 4 examples of penicillinase-resistant penicillins and how are they administered?

A
  1. Nafcillin (parenteral)
  2. Oxacillin (parenteral)
  3. Methicillin (parenteral, lab only)
  4. Dicloxacillin (oral)
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26
Q

Which Gram-positive bacteria are susceptible to penicillinase-resistant penicillins?

A
  1. Methicillin-susceptible S. aureus (MSSA)
  2. Group streptococci
  3. Viridans streptococci
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27
Q

Why were aminopenicillins developed?

A

To improve activity against gram-negative aerobes

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28
Q

What are 2 examples of aminopenicillins and how are they administered?

A
  1. Ampicillin (parenteral, oral)

2. Amoxicillin (oral)

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29
Q

Which Gram-positive bacteria are susceptible to aminopenicillins?

A
  1. Penicillin-susceptible S. aureus
  2. Penicillin-susceptible S. pneumoniae
  3. Group streptococci
  4. Viridans streptococci
  5. Enterococcus spp.
  6. Listeria monocytogenes
30
Q

Which Gram-negative bacteria are susceptible to aminopenicillins?

A
  1. Proteus mirabilis
  2. Some E. coli
  3. Salmonella
  4. Shigella
  5. Beta-lactam negative H. influenzae
31
Q

Why were carboxypenicillins developed?

A

To further improve activity against gram-negative aerobes

32
Q

What is one example of a carboxypenicillin and how is it administered?

A
  1. Ticarcillin (parenteral, not available anymore)
33
Q

Which Gram-negative bacteria are susceptible to carboxypenicillins?

A
  1. Proteus mirabilis
  2. Salmonella
  3. Shigella
  4. Some E. coli
  5. Beta-lactam positive H. influenzae
  6. Enterobacter spp.
  7. Pseudomonas aeruginosa
34
Q

Why were ureidopenicillins developed?

A

To even further enhance activity against gram-negative bacteria

35
Q

What is one example of a ureidopenicillin and how is it administered?

A
  1. Piperacillin (parenteral)
36
Q

Which Gram-positive bacteria are susceptible to ureidopenicillins?

A
  1. Viridans strep
  2. Group strep
  3. Some enterococcus
  4. Anaerobes (fairly good activity)
37
Q

Which Gram-negative bacteria are susceptible to ureidopenicillins?

A
  1. Proteus mirabilis
  2. Salmonella
  3. Shigella
  4. E. coli
  5. Beta-lactam positive H. influenzae
  6. Enterobacter spp.
  7. Pseudomonas aeruginosa
  8. Serratia marcescens
  9. Some Klebsiella spp.
38
Q

How do beta-lactamase inhibitors work?

A

Potent inhibitors of bacterial beta-lactamases; given with penicillins and other beta-lactams to protect them from being hydrolyzed; they bind irreversibly to the catalytic site of beta-lactamase

39
Q

True or false - beta-lactamase inhibitors also have antibacterial activity.

A

False - they have weak to no antibacterial activity.

40
Q

What are 4 examples of beta-lactamase inhibitors?

A
  1. Clavulanate
  2. Sulbactam
  3. Tazobactam
  4. Avibactam
41
Q

What is sulbactam given with?

A

Ampicillin (Unasyn)

42
Q

What is clavulanate given with?

A

Ticarcillin (Timentin, not available); amoxicillin (Augmentin)

43
Q

What is tazobactam given with?

A

Piperacillin (Zosyn)

44
Q

Which Gram-positive bacteria are susceptible to beta-lactamase inhibitor combos?

A
  1. S. aureus (not MRSA)

2. Bacteroides spp. (anaerobes)

45
Q

Which Gram-negative bacteria are susceptible to beta-lactamase inhibitor combos?

A
  1. H. influenzae
  2. E. coli
  3. Proteus spp.
  4. Klebsiella spp.
  5. N. gonorrhoeae
  6. Moraxella catarrhalis
46
Q

What pharmacologic factor correlates with pencillin efficacy?

A

Time above MIC

47
Q

Do penicillins have a post-antibiotic effect (PAE)?

A

Yes, for Gram positive, No for Gram negative

48
Q

Penicilins have synergy with ___ against which bacteria?

A

Aminoglycosides; Enterococcus spp., Staphylococcus spp., viridans strep, Gram-negative bacteria

49
Q

Many penicillins are degraded by ___ and thus are administered ___.

A

Gastric acid; by IV

50
Q

What is the best absorbed oral penicillin?

A

Penicillin VK (still not as good as IV)

51
Q

Ampicillin/sulbactam achieves higher levels than what other combination?

A

Amoxicillin/clavulanate

52
Q

Which oral aminoglycoside is better absorbed?

A

Amoxicillin

53
Q

How are pencillins distributed?

A

Widely into tissues and fluids except eye, prostate, and uninflammed CSF

54
Q

Describe the protein binding of pencillins.

55
Q

How are the PRPs eliminated?

A

Via the liver

56
Q

How can elimination of penicillin be slowed?

A

Administration of probenecid

57
Q

Why do we have to consider sodium when administering parenteral penicillins?

A

Sodium is contained in some preparations and must be used with caution in patients with CHF or renal insufficiency

58
Q

Natural penicillins are the drugs of choice for which bacteria/infections?

A
  1. Pencillin-susceptible S. pneumoniae
  2. Infections due to other streptococci
  3. N. meningitidis
  4. Syphilis
  5. C. perfringens or tetani
  6. Actinomyces
  7. Bacillus anthracis
  8. Endocarditis prophylaxis
  9. Prevention of RF
59
Q

Penicillinase-resistant penicillins are the drugs of choice for which bacteria/infections?

A
  1. Infections due to MSSA (SSSI, septic arthritis, osteomyelitis, bacteremia, endocarditis)
60
Q

Aminopenicillins are the drugs of choice for which bacteria/infections?

A
  1. Respiratory tract infections, pharyngitis, sinusitis, otitis media, bronchitis, UTIs
  2. Enterococcal infections and infections due to Listeria monocytogenes
  3. Endocarditis prophylaxis in selected patients with valvular disease
61
Q

Carboxypenicillins and ureidopenicillins are the drugs of choice for which bacteria/infections?

A
  1. Serious infections due to Gram-negative aerobic bacteria such as pneumonia, bacteremia, complicated UTIs, SSSIs, peritonitis
  2. Hospital-acquired infections
  3. Infection due to Pseudomonas aeruginoas
62
Q

Augmentin is the drug of choice for which bacteria/infections?

A
  1. Sinusitis
  2. Otitis media
  3. Upper and lower respiratory tract infections
  4. Human or animal bite wounds
63
Q

Unasyn, Zosyn, and Timentin are the drugs of choice for which bacteria/infections?

A
  1. Polymicrobial infections (polymicrobial pneumonia - aspiration)
  2. Intra-abdominal infections
  3. Gynecologic infections
  4. Diabetic foot infections
  5. Febrile neutropenia, hospital-acquired infections (Zosyn)
64
Q

Hypersensitivity penicillin reactions are seen in ___% of people.

65
Q

There is a higher incidence of hypersensitivity to penicillins with ___ administration.

A

Parenteral

66
Q

What are some neurologic adverse effects of penicillin?

A

Irritability, jerking, confusion, seizures (especially in patients receiving high IV doses with renal insufficiency)

67
Q

What are some hematologic adverse effects of penicillin?

A

Leukopenia, neutropenia, thrombocytopenia (usually during prolonged therapy, reversible upon discontinuation)

68
Q

What are some GI adverse effects of penicillin?

A

Increased LFTs, nausea, vomiting, diarrhea, pseudomembranous colitis

69
Q

Penicillin can cause interstitial nephritis - what is this?

A

Immune-mediated damage to renal tubules characterized by an abrupt increase in serum creatinine, eosinophilia, eosinophiluria; can lead to renal failure

70
Q

Interstitial nephritis is especially seen with ___.

71
Q

What are three other adverse effects to penicillins?

A
  1. Phlebitis
  2. Hypokalemia
  3. Na+ overload

PT 1 (34 decks)

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