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

Lec. 7: Inhibitors of Cell Wall Synthesis Flashcards

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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
What is the beta-lactamase and penicillin combination that makes up timentin?
Clavulanic acid and ticarcillin
26
What is the beta-lactamase and penicillin combination that makes up zosyn?
Tazobactam and piperacillin
27
What are also referred to as "suicide inhibitors?"
Beta-lactamase inhibitors
28
Absorption of penicillin is dependent on what two things?
1. Acid stability | 2. Protein binding
29
Will the presences of food increase or decrease absorption of penicillin? Name the one exception.
1. Decrease | 2. Amoxicillin
30
Distribution of penicillin is good to most body site. Where is its distribution minimal?
CSF
31
Penicillin is mainly metabolized by ? enzymes.
Hepatic
32
What is the major site of excretion (90%) of penicillins?
Renal via tubular secretion
33
Which four penicillins are penicillanse resistant?
1. Nafcillin 2. Oxacillin 3. Cloxacillin 4. Dicloxacillin
34
T or F. All penicillins are considered narrow spectrum drugs.
True
35
What classification of penicillins have the higher % that are protein bound?
Penicillinase resistant
36
Which penicillins have the longest half life?
Extended spectrum
37
List four ways that the bacteria can become resistant to penicillins?
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
What are two mechanisms used to effectively treat resistance strains?
1. Use beta-lactamase-resistant penicillins | 2. Use beta-lactamse inhibitor
39
What penicillin would be used to treat methicillin-resistant staphylococcal infections?
Vancomycin
40
What are two acute allergic reactions that can occur in adverse reactions to penicillin?
1. Anaphylaxis | 2. Bronchospasm
41
What are some common adverse reactions that occur with penicillins?
1. Nausea and vomiting 2. Diarrhea 3. Adverse effects on plasma electrolyte concentrations 4. Neurotoxicity at large doses 5. Hypersensitivity reactions (allergic reactions)
42
If penicillin G reacts with bacterial amidase, what will the product be?
6-Aminopenicillanic acid
43
If penicillin G reacts with beta-lactamases, what will be the product?
Penicilloic acid
44
Give three examples that would indicate prophylactic use of penicillin.
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
What is the mechanism of action of cephalosporins?
Inhibition of cell wall synthesis by binding to the bacterial transpeptidase enzyme (similar to penicillin).
46
What are three mechanisms of resistance of cephalosporin? | Hint: similar to penicillin
1. Inability to reach target of transpeptidase enzymes 2. Alteration in binding to transpeptidase enzyme 3. Hydrolysis by beta-lactamases
47
T or F. Even 3rd generation cephalosporins are not reliable for organisms producing AmpC-inducible beta-lactamases.
True
48
What are the three generations of cephalosporins?
1. Cephalexin 2. Cefaclor 3. Cefotaxime
49
First generation cephalosporins have a similar spectrum to ? and are most active for gram-? cocci.
1. Ampicillin | 2. Gram-positive
50
Second generation cephalosporins are most active for gram-? cocci.
Gram-negative
51
List three characteristics of third generation cephalosporins.
1. Act on enteric gram-negative organisms 2. Reserve for very serious infections 3. Cross the BBB
52
List three characteristics of fourth generation cephalosporins.
1. Increase activity for gram-positive organisms 2. Beta-lactamase producing organisms 3. Broad spectrum
53
Give two examples of fourth generation cephalosporins.
1. Cefapime | 2. Ceftaroline
54
How many current cephalosporins have activity for Enterococcus?
Zero
55
Progression from 1st to 3rd generation cephalosporins is marked by what four things?
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
How are most cephalosporins absorbed?
Via IV or IM
57
What generation cephalosporin will penetrate to CSF sufficiently to be useful for treatment of meningitis. Give two examples.
Third generation 1. Cefotaxime 2. Ceftriaxone
58
What is the only cephalosporin that does not require extra dose following hemodialysis?
Ceftriaxone
59
What is the major pathway for excretion of cephalosporins?
Renal Tubular pathway
60
Is someone more likely to be allergic to penicillin or cephalosporin?
Penicillin
61
Penicillins can be anaphylactic. How often are cephalosporins anaphylactic?
Rarely
62
Name five adverse reactions to cephalosporins.
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
What binds to the penicillin binding proteins and inhibits cell wall synthesis?
Carbapenems
64
What has a beta-lactam ring, has high resistance to beta-lactamase enzymes, and is a potent "suicide" inactivator of beta-lactamase?
Carbapenems
65
What has the broadest spectrum of any beta-lactam antibiotics and is given IV?
Carbapenems
66
Carbapenems are administered with ?, which acts as an inhibitor of dehydropeptidase, prevents breakdown and renal toxicity, and is in fixed combination with primaxin.
Cilastatin
67
Carbapenems are active against what bacteria, has a role in empiric therapy, and is resistant to nosocomial gram-negatives.
Pseudomonas aeruginosa
68
What carbapenem does not require co-administration with cilastatin and is less likely to cause seizures?
Meropenem
69
What carbapenem has a longer serum half-life, is used for once a day dosing, and is active for gram-positive organisms and anaerobes?
Ertapenem
70
What is the mechanism of action of vancomycin?
Inhibits cell wall synthesis at a DIFFERENT site from other beta-lactams
71
Vancomycin has a ? spectrum that acts against gram-? bacteria and can require resistance by alteration in what binding site?
1. Narrow 2. Positive 3. Peptapeptide binding site
72
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)
D-Ala-D-Lactate
73
Vancomycin does not typically go to the CNS unless what condition is present?
Meninges are inflamed
74
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?
Up to 200 hours
75
"Red man syndrome," nephrotoxicity, ototoxicity, and phlebitis are all adverse effects of what?
Vancomycin
76
T or F. No prophylactic use of Vancomycin unless MRSA is highly suspected.
True
77
What is used as a first line therapy for antibiotic associated colitis?
Metronidazole
78
If a patient tests positive for methicillin-resistant staphylococcus aureus, then what drug should not be used and what drug should be used?
Should not use vancomycin, but can switch to nafcillin
79
"Red man syndrome" is associated with vancomycin and caused by release of what?
Histamine

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