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Pharmacology > Lec. 7: Inhibitors of Cell Wall Synthesis > Flashcards

Lec. 7: Inhibitors of Cell Wall Synthesis Flashcards

1
Q

Name three inhibitors of cell wall synthesis.

A
  1. Penicillins
  2. Cephalosporins
  3. Vancomycin
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2
Q

Which has a thick peptidoglycan layer in their cell wall?

A

Gram positive

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3
Q

What has LPS in their cell wall structure?

A

Gram negative

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4
Q

What do both gram positive and gram negative bacteria cell walls have?

A

Beta-lactamase enzymes and penicillin-binding proteins

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5
Q

Who discovered penicillin?

A

Alexander Flemming

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6
Q

What two scientist proved the value of penicillin as a drug?

A

Chain and Florey

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7
Q

What are the names of the two rings (bicyclic) found in Penicillin?

A
  1. Thiazolidine ring

2. Beta-lactam ring

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8
Q

What ring and bond does Penicillinase act on?

A

Ring: Beta-lactam ring
Bond: C-N

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9
Q

What is the name of the penicillin binding protein that binds the strands together to make the cell wall in bacteria?

A

Transpeptidase - helps form the peptide bridge in peptoglycan cell wall

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10
Q

What are the two main subunits that make up the peptoglycan cell wall?

A

NAM and NAG

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11
Q

What are the four main classifications of penicillins?

A
  1. Natural penicillins
  2. Anti-staphylococcal
  3. Extended spectrum
  4. Anti-pseudomonal
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12
Q

Which classification of penicillins are penicillinase resistant?

A

Anti-staphylococcal

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13
Q

Give two examples of Natural Penicillins.

A
  1. Penicillin G

2. Penicillin V

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14
Q

Give two examples of Anti-staphylococcal penicillins.

A
  1. Nafcillin

2. Oxacillin

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15
Q

Which classification of penicillin is considered a beta-lactamase producing staph?

A

Anti-staphylococcal penicillin

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16
Q

What type of penicillin could be used to treat Streptococcus, Neisseria gonorrhoeae, and Treponema pallidum?

A

Natural Penicillins; more specifically Penicillin V

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17
Q

What classification of penicillin would be used to treat E. coli?

A

Extended spectrum penecillin

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18
Q

Give three examples of anti-pseudomonal penicillins.

A
  1. Ticarcillin
  2. Mezlocillin
  3. Piperacillin
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19
Q

Which classification of penicillin would be used to treat Pseudomonas aeruginosa?

A

Anti-pseudomonal penicillin

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20
Q

Why would a beta-lactamase inhibitor be given in combination with penicillin?

A

Beta-lactamase inhibitors are given in combination with penicillin because without the beta-lactam ring, the penicillin (antibiotic) would NOT have anywhere to bind and perform its action.

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21
Q

Name three beta-lactamase inhibitors.

A
  1. Clavulanic acid
  2. Sulbactam
  3. Tazobactam
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22
Q

Name four beta-lactamase inhibitor/penicillin combinations.

A
  1. Augmentin
  2. Unasyn
  3. Timentin
  4. Zosyn
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23
Q

What is the beta-lactamase and penicillin combination that makes up augmentin?

A

Clavulanic Acid and Amoxicillin

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24
Q

What is the beta-lactamase and penicillin combination that makes up unasyn?

A

Sulbactam and ampicillin

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25
Q

What is the beta-lactamase and penicillin combination that makes up timentin?

A

Clavulanic acid and ticarcillin

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26
Q

What is the beta-lactamase and penicillin combination that makes up zosyn?

A

Tazobactam and piperacillin

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27
Q

What are also referred to as “suicide inhibitors?”

A

Beta-lactamase inhibitors

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28
Q

Absorption of penicillin is dependent on what two things?

A
  1. Acid stability

2. Protein binding

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29
Q

Will the presences of food increase or decrease absorption of penicillin? Name the one exception.

A
  1. Decrease

2. Amoxicillin

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30
Q

Distribution of penicillin is good to most body site. Where is its distribution minimal?

A

CSF

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31
Q

Penicillin is mainly metabolized by ? enzymes.

A

Hepatic

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32
Q

What is the major site of excretion (90%) of penicillins?

A

Renal via tubular secretion

33
Q

Which four penicillins are penicillanse resistant?

A
  1. Nafcillin
  2. Oxacillin
  3. Cloxacillin
  4. Dicloxacillin
34
Q

T or F. All penicillins are considered narrow spectrum drugs.

A

True

35
Q

What classification of penicillins have the higher % that are protein bound?

A

Penicillinase resistant

36
Q

Which penicillins have the longest half life?

A

Extended spectrum

37
Q

List four ways that the bacteria can become resistant to penicillins?

A
  1. Production of beta-lactamases
  2. Inability of penicillins to penetrate site of action
  3. Inability of penicillins to bind to the penicillin binding protein
  4. Lack of activation of autolytic enzymes
38
Q

What are two mechanisms used to effectively treat resistance strains?

A
  1. Use beta-lactamase-resistant penicillins

2. Use beta-lactamse inhibitor

39
Q

What penicillin would be used to treat methicillin-resistant staphylococcal infections?

A

Vancomycin

40
Q

What are two acute allergic reactions that can occur in adverse reactions to penicillin?

A
  1. Anaphylaxis

2. Bronchospasm

41
Q

What are some common adverse reactions that occur with penicillins?

A
  1. Nausea and vomiting
  2. Diarrhea
  3. Adverse effects on plasma electrolyte concentrations
  4. Neurotoxicity at large doses
  5. Hypersensitivity reactions (allergic reactions)
42
Q

If penicillin G reacts with bacterial amidase, what will the product be?

A

6-Aminopenicillanic acid

43
Q

If penicillin G reacts with beta-lactamases, what will be the product?

A

Penicilloic acid

44
Q

Give three examples that would indicate prophylactic use of penicillin.

A
  1. Individual exposed to gonorrhea or syphilis
  2. Prevention of recurrence of rheumatic fever
  3. Patients with valvular heart disease that are undergoing surgery OR dental extraction
45
Q

What is the mechanism of action of cephalosporins?

A

Inhibition of cell wall synthesis by binding to the bacterial transpeptidase enzyme (similar to penicillin).

46
Q

What are three mechanisms of resistance of cephalosporin?

Hint: similar to penicillin

A
  1. Inability to reach target of transpeptidase enzymes
  2. Alteration in binding to transpeptidase enzyme
  3. Hydrolysis by beta-lactamases
47
Q

T or F. Even 3rd generation cephalosporins are not reliable for organisms producing AmpC-inducible beta-lactamases.

A

True

48
Q

What are the three generations of cephalosporins?

A
  1. Cephalexin
  2. Cefaclor
  3. Cefotaxime
49
Q

First generation cephalosporins have a similar spectrum to ? and are most active for gram-? cocci.

A
  1. Ampicillin

2. Gram-positive

50
Q

Second generation cephalosporins are most active for gram-? cocci.

A

Gram-negative

51
Q

List three characteristics of third generation cephalosporins.

A
  1. Act on enteric gram-negative organisms
  2. Reserve for very serious infections
  3. Cross the BBB
52
Q

List three characteristics of fourth generation cephalosporins.

A
  1. Increase activity for gram-positive organisms
  2. Beta-lactamase producing organisms
  3. Broad spectrum
53
Q

Give two examples of fourth generation cephalosporins.

A
  1. Cefapime

2. Ceftaroline

54
Q

How many current cephalosporins have activity for Enterococcus?

A

Zero

55
Q

Progression from 1st to 3rd generation cephalosporins is marked by what four things?

A
  1. Broadening in gram-negative bacterial susceptibility
  2. Diminution of activity against gram + bacteria
  3. Increased resistance to beta-lactamase interaction
  4. Increased capability to enter CSF
56
Q

How are most cephalosporins absorbed?

A

Via IV or IM

57
Q

What generation cephalosporin will penetrate to CSF sufficiently to be useful for treatment of meningitis. Give two examples.

A

Third generation

  1. Cefotaxime
  2. Ceftriaxone
58
Q

What is the only cephalosporin that does not require extra dose following hemodialysis?

A

Ceftriaxone

59
Q

What is the major pathway for excretion of cephalosporins?

A

Renal Tubular pathway

60
Q

Is someone more likely to be allergic to penicillin or cephalosporin?

A

Penicillin

61
Q

Penicillins can be anaphylactic. How often are cephalosporins anaphylactic?

A

Rarely

62
Q

Name five adverse reactions to cephalosporins.

A
  1. Sever pain with intramuscular injections
  2. Diarrhea and GI disturbances
  3. Phlebitis from IV administration
  4. Nephrotoxicity at high doses
  5. There are disulfiram-like effects with alcohol (cephalosporin must contain specific side chain; ex. cefotetan)
63
Q

What binds to the penicillin binding proteins and inhibits cell wall synthesis?

A

Carbapenems

64
Q

What has a beta-lactam ring, has high resistance to beta-lactamase enzymes, and is a potent “suicide” inactivator of beta-lactamase?

A

Carbapenems

65
Q

What has the broadest spectrum of any beta-lactam antibiotics and is given IV?

A

Carbapenems

66
Q

Carbapenems are administered with ?, which acts as an inhibitor of dehydropeptidase, prevents breakdown and renal toxicity, and is in fixed combination with primaxin.

A

Cilastatin

67
Q

Carbapenems are active against what bacteria, has a role in empiric therapy, and is resistant to nosocomial gram-negatives.

A

Pseudomonas aeruginosa

68
Q

What carbapenem does not require co-administration with cilastatin and is less likely to cause seizures?

A

Meropenem

69
Q

What carbapenem has a longer serum half-life, is used for once a day dosing, and is active for gram-positive organisms and anaerobes?

A

Ertapenem

70
Q

What is the mechanism of action of vancomycin?

A

Inhibits cell wall synthesis at a DIFFERENT site from other beta-lactams

71
Q

Vancomycin has a ? spectrum that acts against gram-? bacteria and can require resistance by alteration in what binding site?

A
  1. Narrow
  2. Positive
  3. Peptapeptide binding site
72
Q

Vancomycin bacteria have become more resistant by substituting D-Ala-D-Ala for what? This causes the vancomycin to spend more time NOT bound to the bacteria b/c of the mutation (3 H bonds vs 2 H bonds)

A

D-Ala-D-Lactate

73
Q

Vancomycin does not typically go to the CNS unless what condition is present?

A

Meninges are inflamed

74
Q

It is important to look at the patients kidney functions when giving vancomycin because during normal renal function the T1/2 is 4-6 hours, but with renal impairment the T1/2 can be up to what?

A

Up to 200 hours

75
Q

“Red man syndrome,” nephrotoxicity, ototoxicity, and phlebitis are all adverse effects of what?

A

Vancomycin

76
Q

T or F. No prophylactic use of Vancomycin unless MRSA is highly suspected.

A

True

77
Q

What is used as a first line therapy for antibiotic associated colitis?

A

Metronidazole

78
Q

If a patient tests positive for methicillin-resistant staphylococcus aureus, then what drug should not be used and what drug should be used?

A

Should not use vancomycin, but can switch to nafcillin

79
Q

“Red man syndrome” is associated with vancomycin and caused by release of what?

A

Histamine

Pharmacology (9 decks)

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