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Inhibitors of Cell Wall Synthesis Flashcards

1
Q

Synonym for Inhibitors of Cell Wall synthesis drugs?

A

Beta-Lactam antibiotics

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2
Q

What is specific structure of penicillin?

A

Beta Lactam ring = 4 membered ring

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3
Q

What is important about beta lactam ring in penicillin?

A

It is strained, therefore reactive

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4
Q

What is cephalosporin?

A

A fungally derived drug with a beta lactam ring (penicillin is bacterial derived)

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5
Q

What is the characteristic of the beta lactam ring if it is broken?

A

It will not work

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6
Q

What type of bacteria are cell-wall synthesis inhibitors most effective against?

A

Most gram positive, some gram negative

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7
Q

What bacteria are Inhibitors of Cell-Wall synthesis drugs effective against (3 specific)?

A

Spirochete, treponema palidum (syphilis) and actinomycoses

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8
Q

What organisms are Inhibitors of Cell Wall synthesis drugs not effective against (5)?

A

Protozoa, fungi, viruses, tubercule bacillus and rickettsia

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9
Q

When are inhibitors of Cell Wall synthesis most effective?

A

During early infection when bacteria are actively dividing and building cell wall

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10
Q

What does a bacterial cell wall do (very general)?

A

Encases bacterial cell membrane; after water flows in, the cell wall becomes rigid

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11
Q

What is the general fluid [ ] of cell interior of gram positive bacteria?

A

Hypertonic

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12
Q

What does penicillin inhibit in bacteria?

A

Inhibits cross linking of cell wall units

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13
Q

What happens when the cell wall has holes punched in it by beta lactam drugs?

A

Membrane ruptures due to inflow of water to hypertonic cell causing rupture

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14
Q

What is required on the bacteria to aide the beta lactam drugs?

A

Bacterial surface enzymes (autolysins) that cleave previously synthesized cell wall; these are usually reserved for reproduction

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15
Q

In the absence of bacterial autolysins what is the character of Beta Lactam drugs: bacteriocidal or bacteriostatic.

A

Bacteriostatic

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16
Q

What are the three stages of bacterial cell wall synthesis?

A
  1. Production of cell wall building blocks
  2. Precursor carried from inside cell membrane to
    outside
  3. Cross linking of cell wall
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17
Q

Which Beta lactam drug inhibits the production of Cell Wall Building blocks (Stage I)? Treats what infection?

A

Cycloserine; tuberculosis

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18
Q

What 2 beta lactam drugs inhibit the precursors being carried from inside the cell membrane to the outside (Stage II)?

A

Vancomycin and bacitracin

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19
Q

What 2 beta lactam drugs stop the cross-linking of the cell wall (Stage III)?

A

Penicillin and cephalosporin

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20
Q

How does penicillin inhibit the cross linking of the cell wall?

A

It is similar to the D-alanyl-D-alanyl terminus of polypeptide side chain of peptidoglycan and occupies D- ala-D-ala substrate site of transpeptide

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21
Q

Beta lactam antibiotics interfere with what steps of cell wall synthesis?

A

Final steps

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22
Q

What do autolysins normally do (2)?

A

Normally nick cell walls for attachment of new peptidoglycan units or separation of daughter cells

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23
Q

Four ways bacteria can become resistant to Penicillin

A
  1. Lack of accessibility to target
  2. Production of penicillinases or beta lactamases
  3. Altered penicillin binding protein
  4. Drug efflux pumps
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24
Q

What is an example of lack of accessibility to target for penicillin resistance?

A

Gram negative bacteria having outer membrane inhibiting access to cell wall

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25
What is absolute requirement for inhibition of transpeptidase?
Intact beta-lactam ring
26
What is the difference between beta-lactamase and penicillinase?
Penicillinase only breaks down penicillin beta lactam ring
27
How can gram negative bacteria, who have low production of penicillinases still eliminate antibiotic without being swamped?
Gram negative limits access of beta lactam antibiotics via the peptidoglycan cell wall
28
If an antibiotic binds to Penicillin Binding Protein 2 or Penicillin Binding Protein 3 what will its effects be on the bacteria?
Prevents cell division (septum formation) and loss of rod like structure (filament formation)
29
What do PBP 2 and 3 do specifically?
3: Septum formation (cleave in rod) 2: Needed for rod shape
30
What does binding to PBP 1 affect?
Inhibits synthesis of cell wall so organism undergoes osmotic lysis
31
If Ab binds PBP 2 and 3, is the effect bacteriostatic or -cidal? PBP 1?
Static; PBP 1 is bacteriocidal
32
In what stage of cell wall synthesis is PBP 1 involved?
Cross linking step on Stage III of cell wall synthesis
33
What can PBP 1 do to itself to resist penicillin?
Change its affinity for penicillin
34
What will happen if bacteria increases levels of Penicillin binding protein?
It will soak up the penicillin to decrease the effect of penicillin on PBP 1
35
What else can bacteria do to alter their penicillin binding protein to resist penicillin?
Synthesize new PBP’s with altered penicillin affinity
36
What does a drug efflux pump do?
Pumps out the drug once it gets into the cell
37
What is characteristic of broad spectrum penicillin versus narrow spectrum penicillin?
Broad spectrum can be effective against some gram negatives by getting through the Outer envelope of gram negative bacteria to attack transpeptidases in cell wall
38
Are penicillins widely distributed or narrowly distributed throughout the body?
Widely distributed
39
Where do penicillins not distribute well and therefore cannot be used for treatment in these areas of the body?
Joints, ocular tissue, cerebrospinal fluid
40
What can cause penicillin to reach higher levels in the central nervous system?
Inflammation
41
What administrative route is most common parenteral route that gives predictable blood level for penicillin?
Intramuscular
42
What penicillin administrative route to use for treatment of severe infection requiring fast action and high blood levels?
Intravenous
43
How much penicillin is absorbed by oral administration?
20-25%
44
How is penicillin eliminated?
Renal
45
What fraction of penicillin is excreted as a still active drug? Half life?
2/3; ~1hr
46
Why is probenecid used?
Decreases renal excretion of drugs to increase antibiotic plasma concentration during serious infection
47
Use of penicillin is limited primarily by ___?
Resistance
48
Five toxicities ass'd w/ penicillin?
Resistance, hypersensitivity, anaphylactic shock, CNS effects or superinfection
49
Staph infections acquired in hospital are usually susceptible or resistant to penicillin?
Resistant
50
What respiratory problem increases one’s risk of penicillin hypersensitivity?
Asthma
51
Would a penicillin hypersensitivity result in anaphylaxis?
No, just a rash
52
What would be six signs of penicillin anaphylaxis?
Bronchoconstriction, abdominal pain, nausea, vomiting, weakness, fall in BP
53
What are immediate indicators of anaphylaxis?
Dizziness, weakness, sweating and palpitations
54
After a sensitization dose to penicillin, what are likely symptoms?
Rash, fever, swollen joints several days after taking penicillin
55
When would a person be at risk for penicillin to affect CNS?
Pt has impaired renal function or infused w/ unusually high dose
56
What is the major risk w/ long-term penicillin therapy?
Superinfection
57
4 General classes of penicillins?
Pencillin G (benzylpenicillin), Gastric-acid-resistant penicillin, penicillinase-resistant pencillin, or broad-spectrum penicillin
58
Standard reference penicillin?
Pencillin G (benzylpenicillin)
59
Is Penicillin G adminstered orally?
No, inactive at low pH
60
Can penicillin G get by penicillinases in bacteria, e.g. against Staph aureus?
No, pencillinase sensitive
61
Is penicillin G broad or narrow spectrum?
Narrow, gram + only (similar to Pen V)
62
Penicillin G are used in the treatment of what three bacterial infections?
Syphillis, rheumatic fever and gonorrhea
63
Name for Gastric Acid Resistant Penicillin?
Penicillin V (acid stable)
64
SIgnificance of Penicillin V?
Can be given orally and produces higher blood levels than Penicillin G (2-5x)
65
4 Penicillinase-Resistant Penicillins?
Methicillin, cloxacillin, nafcillin, dicloxacillin
66
Advantage and disadvantage of Penicillinase Resistant Penicillins?
Less susceptible to penicillinases; narrow spectrum
67
Methicillin (penicillinase resistant penicillin) is oral or IV admin?
IV. Not absorbed orally
68
Is Methicillin as effective as Penicillin G against organisms not producing penicillinase?
No, only 50% as effective as Pen G
69
3 Broad Spectrum Penicillins?
Ampicillin, amoxicillin, and carbenicillin
70
What are Broad-Spectrum Penicillins more active against, Gram - or Gram +?
Gram -, reduced against gram +
71
Are Broad Spectrum Penicillins susceptible to penicillinases?
Yes
72
What is the penicillin-related drug that is front line for tuberculosis treatment?
Cycloserine
73
Which stage of cell wall synthesis does the anti- tuberculosis drug Cycloserine target?
First stage
74
What penicillinase-resistant penicillin can be given orally?
Dicloxacillin
75
This penicillin-related drug is last line of defense treating MRSA and also used in Endocarditis.
Vancomycin
76
Only place Vancomycin administered?
Hospital
77
Which stage of Cell Wall synthesis does Vancomycin inhibit?
Intermediate
78
This intermediate stage cell wall synthesis inhibitor is toxic systemically, but used topically? What type of bac does it kill: gram + or -?
Bacitracin; gram +
79
Bacitracin normally paired with what other 2 drugs as a topical ointment (triple-biotic, Neosporin)?
Polymyxin and neomycin
80
3 agents that can be given in combination with Penicillin or Cephalosporin to increase their activity by breaking down bacterial resistant Beta-lactamase or Penicillinase?
Clavulanate, sulfabactam and taxobactam
81
Cephalosporins are cell wall inhibitors that are bacterial or fungal derived?
Fungal
82
Cephalosporins are resistant to...
Pencillinase
83
How are Cephalosporins and penicillins similar?
Both have beta-lactam rings
84
What bacteria types are Cephalosporins effective against?
Gram + and -
85
Most cephalosporins are administered IV or IM. Which 2 cephalosporins are administered orally?
Cephalexin and cefaclor
86
What is the distribution for Cephalosporins?
Well-distributed except CNS
87
Are most cephalosporins readily metabolized or minimally metabolized?
Minimally metabolized
88
How are cephalosporins excreted?
Kidney
89
2 things that can block cephalosporin excretion in the kidney?
Probenecid (med specifically given to decrease excretion to increase drug potency) and renal failure
90
What causes the hypersensitivity in penicillin and cephalosporins?
Beta-lactam ring
91
Adverse reaction of cephalosporins systemically
Nephrotoxicity
92
3 infections Cephalosporins used for?
Meningitis, streptococcal, staphylococcal
93
Why use Cephalosporin?
Gram - infection that is penicillin resistant
94
When is Cephalosporin used prophylactically?
During and after surgery for endocarditis
95
3 classifications of Cephalosporins
1st, 2nd and third generations
96
2 characteristics of 1st Generation Cephalosporins?
Good against G+, modest against G-
97
First Generation Cephalosporin that can be administered orally?
Cephalexin
98
2 characteristics of 2nd Generation Cephalosporins?
Good against G-. not very active against G+
99
2 characteristics of 3rd Generation Cephalosporins?
Active against G-, especially those producing penicillinase
100
3 ways bacteria can be Cephalosporin resistant?
Drug can't reach target, produce enzyme to disrupt active ring or alter ab binding protein
101
Pseudomonas and proteus Gram negative bacteria can produce this for Cephalosporin resistance.
Cephalosporinase

Pharm Exam 4 (4 decks)

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