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Inhibitors of Cell Wall Synthesis Flashcards

1
Q

Peptidoglycan is composed of:

A

A backbone of two alternating sugars, NAG and NAM,
A chain of four amino acids that are linked to NAM
A peptide bridge that cross links the tetrapeptide chains

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2
Q

Peptidoglycan Synthesis and Abx that prevent the steps

A
  1. Transglycosylation: Joining NAM-NAG (PCNs)
  2. Transpeptidation: Cross links pentapeptides (PCNs)
  3. NAG reduction to NAM (fosfomycin)
  4. Transport across the inner membrane (Bacitracin)
  5. Amino acid mimicry: Pentapeptide chain (Vancomycin)
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3
Q

Target of Beta-lactams

A

PBPs: involved in Transpeptidation/Transglycosylation

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4
Q

Should not be used with ICWS

A

Inhibitor of protein synthesis, b/c this stops cell growth which is necessary for ICWS to work

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5
Q

Beta-lactam Drugs

A

PCNs
Cephalosporins
Monobactams
Carbapenems

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6
Q

ICWS that are NOT beta-lactams

A

Vancomycin
Fosfomycin
Bacitracin

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7
Q

Natural PCNs

A 
Pen G (IV/IM)
Pen V (oral)
Benzathine Pen (IM)
Procaine Pen G (IM)
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8
Q

Penicillinase Resistant PCNs

A

Nafcillin (IM/IV)
Dicloxacillin (Oral)
Oxacillin (Oral)
*Methacillin (TESTING ONLY!)

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9
Q

Extended Spectrum PCNs

A

Ampicillin (Oral)

Amoxicillin (Oral)

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10
Q

Antipseudomonal PCNs

A

Piperacillin

Ticarcillin

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11
Q

Penicillinase MOA

A

Hydrolyzes beta-lactam ring of PCNs, so it can’t bind PBPs

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12
Q

Natural PCN spectrum

A

Mostly G+, some G-

Pen G is the Gold standard for G+ infections

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13
Q

Natural PCN Resistance

A

Penicillinase producing bacteria (S. aureus)

No antipseudomonal activity

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14
Q

Natural PCN Metabolism

A

Active transport in kidney - can be slowed with probenecid

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15
Q

PCNase resistant PCN Spectrum

A

Less G+ than natural, but more G-

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16
Q

PCNase resistant PCN Use

A

MSSA (DOC) - resistance to penicillinase

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17
Q

PCNase resistant PCN Metabolism

A

Hepatic metabolism

Renal excretion

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18
Q

MSSA mechanism of resistance

A

Penicillinase production

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19
Q

MRSA mechanism of resistance

A

Changes PBP which decreases infinity of beta-lactam abx to PBPs.
NO beta-lactam can be used to treat MRSA except CEFTAROLINE (not the DOC)!

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20
Q

MRSA DOC

A

Vancomycin

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21
Q

Extended Spectrum PCN Spectrum

A

Less G+, but extended G- coverage (E. coli, Salmonella, Shigella, H. influenzae, Proteus)
NO Antipseudomonal activity

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22
Q

Extended Spectrum PCN Resistance

A

Resistance develops frequently!

Susceptible to penicillinase

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23
Q

Extended Spectrum PCN Metabolism

A

Urinary excretion

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24
Q

Extended Spectrum PCN Use

A

Lysteria (DOC)

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25
Q

Extended Spectrum PCN Adverse Rxn

A

Ampicillin rash - Not hypersensitivity rxn

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26
Q

Antipseudomonal PCN Spectrum

A

Same as extended spectrum PLUS some additional enteric gram negative bacilli (Proteus, Enterobacter, providencia, and Serratia)

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27
Q

Antipseudomonal PCN Use

A

Pseudomonas aeruginosa (DOC)
Acinetobacter
MUST USE WITH AMINOGLYCOSIDES

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28
Q

Antipseudomonal PCN Resistance

A

Penicillinase (use penicillinase inhibitor)

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29
Q

Antipseudomonal PCN Metabolism

A

Renal excretion

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30
Q

Beta-lactamase inhibitors

A

Clavulanic acid
Sulbactam
Tazobactam

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31
Q

Drugs used with beta-lactamase

A

Amoxicillin
Ampicillin
Piperacillin
Ticarcillin

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32
Q

Resistance to PCNs

A

Inactivation of PCN by penicillinase (ie. MSSA)
Decreased permeability (ie. G-)
Alterations in PBPs (ie. MRSA)
Non-growing bacteria or autolytic enzymes not being activated (ie. Listeria, Staphlyocci)
Lack of cell wall (ie. Mycoplasma, Chlamydia)

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33
Q

PCN Toxicity

A

ALLERGY
Electrolyte imbalances
GI disturbances
Superinfections

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34
Q

PCN Pharmacokinetics

A

Good tissue penetration
Poor CNS penetration (unless inflammation)
Mostly renal elimination
Filtration and tubular excretion - Probenecid can inhibit renal elimination!

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35
Q

Cephalosporin MOA

A

Blocking of terminal cross-linking of peptidoglycans

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36
Q

Advantage of Cephalosporins

A

7-methyl group increases resistance to penicillinase

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37
Q

First Generation Cephalosporin Drugs

A

Cefazolin (IV/IM)

Cephalexin (Oral)

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38
Q

First Generation Cephalosporin Spectrum

A

“Narrow Spectrum”
Good G+; Moderate G- (E. coli, Klebsiella, Proteus)
Most G+ cocci are susceptible, MSSA! - Alternative for PCN allergic individuals

39
Q

First Generation Cephalosporin Use

A

Cefazolin is DOC for surgical prophylaxis

MSSA! - Alternative for PCN allergic individuals

40
Q

First Generation Cephalosporin Metabolism

A

Renal excretion

41
Q

Second Generation Cephalosporin Drugs

A

Cefaclor (Oral)
Cefuroxime (IV/IM)
Cefprozil (Oral)
“A U Pretty”

42
Q

Second Generation Cephalosporin Spectrum

A

“Intermediate Spectrum”
Lower activity against G+ with increased against G-
NO Antipsuedomonal activity

43
Q

Second Generation Cephalosporin Metabolism

A

Renal excretion

44
Q

Third Generation Cephalosporin Drugs

A 
Ceftriaxone (IV/IM)
Cefotaxime Sodium (IV/IM)
Ceftazidime (IV/IM)
Cefixime (Oral)
"Try Taxing Tazmanian Idiots"
45
Q

Third Generation Cephalosporin Spectrum

A

“Broad Spectrum”
Less active against G+ cocci
Much more active against Enterobacteriaceae (penicillinasae producing strains)
P. AERUGINOSA activity (Ceftazidime combined w/ aminoglycosides)

46
Q

Third Generation Cephalosporin Metabolism

A

Excreted by the kidney

47
Q

DOC for N. gonorrhoeae

A

Ceftriaxone

48
Q

Cephalosporins with CNS penetration

A

Ceftriaxone and Ceftazidime

49
Q

Cephalosporin that treats P. aeruginosa

A

Ceftazidime - MUST combine with aminoglycoside

50
Q

Ceftriaxone contraindication

A

Neonates - causes bilirubin displacement

51
Q

Fourth Generation Cephalosporin Drugs

A

Cefepime (IV)

52
Q

Fourth Generation Cephalosporin Spectrum

A

Comparable to 3rd generation… But better!
Better G+ coverage
Antispeudomonal
More resistant to beta-lactamases

53
Q

Fourth Generation Cephalosporin Use

A

Empirical therapy - When you have no clue what bacteria is causing the infection, and it is life threatening!

54
Q

Fourth Generation Cephalosporin Metabolism

A

Renal excretion

55
Q

Fifth Generation Cephalosporin Drugs

A

Ceftaroline fosamil (IV)

56
Q

Fifth Generation Cephalosporin Spectrum

A

G+ and G- activity

NO antipseudomonal activity

57
Q

Fifth Generation Cephalosporin Use

A

MRSA/VRSA (when vancomycin doesn’t work)
Only beta-lactam active against MRSA! - Can bind PBP2A
Approved for CAP

58
Q

Antipseudomonal Beta-lactams

A

Antipseudomonal PCNs
3rd generation cephalosporins
4th generation cephalosporins

59
Q

M. catarrhalis DOC

A

2nd or 3rd generation cephalosporin

60
Q

N. gonorrhoeae DOC

A

Ceftriaxone or Cefixime

61
Q

E. coli, Klebsiella, Proteus DOC

A

1st or 2nd generation cephalosporin

62
Q

Salmonella DOC

A

3rd generation cephalosporin

63
Q

PCN-resistant S. pneumo DOC

A

Ceftriaxone

64
Q

Borrelia burgdorferi late disease DOC

A

Ceftriaxone

65
Q

Cephalosporin Toxicity

A 
Fairly safe...
Superinfection
DISULFIRAM-LIKE RXN
Allergy (10% cross sensitivity w/ PCN)
GI upset
Dose DEPENDENT renal tubular necrosis (Synergistic nephrotoxicity with Aminoglycosides)
66
Q

Monobactam Drugs

A

Aztreonam (parenteral)

67
Q

Aztreonam Spectrum

A

ONLY Aerobic G- rods!
ie. Pseudomonas, Serratia, Klebsiella, Proteus
NO ACTIVITY against G+ or anaerobes

68
Q

Aztreonam Adverse Rxns

A

Few side effects…

Phlebitis, rash, abnormal liver function

69
Q

Aztreonam Use

A

Good for PCN allergic (no cross sensitivity w/ other beta-lactams)

70
Q

Carbapenem Drugs

A

Imipenem (IV); Cilastin
Meropenem (IV)
Ertapenem (IV/IM)
“I, ME”

71
Q

What is cilastin?

A

A dihydropeptidase inhibitor

72
Q

Why is imipenem given with cilastin?

A

Imipenem is rapidly inactivated by renal tubule dihydropeptidases. Cilastin blocks these.
***Meropenem is NOT inactivated by dihydropeptidases!

73
Q

Imipenem and Meropenem Spectrum

A

BROAD spectrum including anaerobes, G+ and G-
Great for empirical therapy!
Stable against beta-lactamases

74
Q

Imipenem and Meropenem Use

A

Mixed infections

Empirical therapy

75
Q

Imipenem Contraindications

A

It can cause seizures in HIGH levels, so should be avoided in…
Renal failure
Brain lesions
Head trauma
Hx of CNS disorders
***Meropenem is less likely to cause seizures!

76
Q

Imipenem is DOC for…?

A

Beta-lactamse producing Enterobacter infections

77
Q

Ertapenem Spectrum

A

Wide variety of G+, G-, and anaerobic microorganisms, particularly Enterobacteriaceae
Highly stable against beta-lactamases
Less active against Pseudomonas, should NOT be used!

78
Q

Ertapenem Metabolism

A

Renal elimination

79
Q

Vancomycin MOA

A

Prevents transpeptidation of the peptidoglycan chain by binding to the terminal D-ala-D-ala.
Bactericidal

80
Q

Vancomycin Resistance

A

Mutation of the terminal D-ala site

81
Q

Vancomycin Use

A 
MRSA (DOC) - IV
C. Diff (DOC) - orally
Staphylococcus superinfection - orally
G+ infections in PCN-allergic patients
Should be used as a LAST RESORT to prevent resistance!
82
Q

Vancomycin Spectrum

83
Q

Vancomycin Adverse Reactions

A

Ototoxicity
Nephrotoxicity
“Red man” Syndrome
Thrombophlebitis on IV injection

84
Q

Fosfomycin MOA

A

Inhibits cell wall synthesis at one of the first steps of peptidoglycan synthesis:
Prevents NAG to NAM reduction in cytoplasm

85
Q

Fosfomycin Spectrum

A

G+ and G- (broad?)

86
Q

Fosfomycin Administration

87
Q

Fosfomycin Use

A

Uncomplicated UTI (not the DOC)

88
Q

Fosfomycin is synergistic with what?

A

Beta-lactam, aminoglycoside, or fluoroquinolone!

89
Q

Fosfomycin Metabolism

A

Excreted by the kidney

90
Q

Bacitracin MOA

A

Interferes with final dephosphorylation step in the phospholipid carrier cycle:
Can’t transfer NAG-NAM across the inner membrane

91
Q

Bacitracin Administration

A

Typically topical (used in neosporin), rarely parenteral (risk of nephrotoxicity)

92
Q

Bacitracin Spectrum

93
Q

Bacitracin Use

A

Most commonly used topically to prevent superficial skin and eye infections following minor injuries

Pharmacology Exam 2 (4 decks)

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