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Inhibitors of Cell Wall Synthesis Flashcards

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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
Extended Spectrum PCN Adverse Rxn
Ampicillin rash - Not hypersensitivity rxn
26
Antipseudomonal PCN Spectrum
Same as extended spectrum PLUS some additional enteric gram negative bacilli (Proteus, Enterobacter, providencia, and Serratia)
27
Antipseudomonal PCN Use
Pseudomonas aeruginosa (DOC) Acinetobacter *MUST USE WITH AMINOGLYCOSIDES*
28
Antipseudomonal PCN Resistance
Penicillinase (use penicillinase inhibitor)
29
Antipseudomonal PCN Metabolism
Renal excretion
30
Beta-lactamase inhibitors
Clavulanic acid Sulbactam Tazobactam
31
Drugs used with beta-lactamase
Amoxicillin Ampicillin Piperacillin Ticarcillin
32
Resistance to PCNs
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)
33
PCN Toxicity
ALLERGY Electrolyte imbalances GI disturbances Superinfections
34
PCN Pharmacokinetics
Good tissue penetration Poor CNS penetration (unless inflammation) Mostly renal elimination Filtration and tubular excretion - Probenecid can inhibit renal elimination!
35
Cephalosporin MOA
Blocking of terminal cross-linking of peptidoglycans
36
Advantage of Cephalosporins
7-methyl group increases resistance to penicillinase
37
First Generation Cephalosporin Drugs
Cefazolin (IV/IM) | Cephalexin (Oral)
38
First Generation Cephalosporin Spectrum
"Narrow Spectrum" Good G+; Moderate G- (E. coli, Klebsiella, Proteus) Most G+ cocci are susceptible, MSSA! - Alternative for PCN allergic individuals
39
First Generation Cephalosporin Use
Cefazolin is DOC for surgical prophylaxis | MSSA! - Alternative for PCN allergic individuals
40
First Generation Cephalosporin Metabolism
Renal excretion
41
Second Generation Cephalosporin Drugs
Cefaclor (Oral) Cefuroxime (IV/IM) Cefprozil (Oral) "A U Pretty"
42
Second Generation Cephalosporin Spectrum
"Intermediate Spectrum" Lower activity against G+ with increased against G- NO Antipsuedomonal activity
43
Second Generation Cephalosporin Metabolism
Renal excretion
44
Third Generation Cephalosporin Drugs
``` Ceftriaxone (IV/IM) Cefotaxime Sodium (IV/IM) Ceftazidime (IV/IM) Cefixime (Oral) "Try Taxing Tazmanian Idiots" ```
45
Third Generation Cephalosporin Spectrum
"Broad Spectrum" Less active against G+ cocci Much more active against Enterobacteriaceae (penicillinasae producing strains) P. AERUGINOSA activity (Ceftazidime combined w/ aminoglycosides)
46
Third Generation Cephalosporin Metabolism
Excreted by the kidney
47
DOC for N. gonorrhoeae
Ceftriaxone
48
Cephalosporins with CNS penetration
Ceftriaxone and Ceftazidime
49
Cephalosporin that treats P. aeruginosa
Ceftazidime - MUST combine with aminoglycoside
50
Ceftriaxone contraindication
Neonates - causes bilirubin displacement
51
Fourth Generation Cephalosporin Drugs
Cefepime (IV)
52
Fourth Generation Cephalosporin Spectrum
Comparable to 3rd generation... But better! Better G+ coverage Antispeudomonal More resistant to beta-lactamases
53
Fourth Generation Cephalosporin Use
Empirical therapy - When you have no clue what bacteria is causing the infection, and it is life threatening!
54
Fourth Generation Cephalosporin Metabolism
Renal excretion
55
Fifth Generation Cephalosporin Drugs
Ceftaroline fosamil (IV)
56
Fifth Generation Cephalosporin Spectrum
G+ and G- activity | NO antipseudomonal activity
57
Fifth Generation Cephalosporin Use
MRSA/VRSA (when vancomycin doesn't work) Only beta-lactam active against MRSA! - Can bind PBP2A Approved for CAP
58
Antipseudomonal Beta-lactams
Antipseudomonal PCNs 3rd generation cephalosporins 4th generation cephalosporins
59
M. catarrhalis DOC
2nd or 3rd generation cephalosporin
60
N. gonorrhoeae DOC
Ceftriaxone or Cefixime
61
E. coli, Klebsiella, Proteus DOC
1st or 2nd generation cephalosporin
62
Salmonella DOC
3rd generation cephalosporin
63
PCN-resistant S. pneumo DOC
Ceftriaxone
64
Borrelia burgdorferi late disease DOC
Ceftriaxone
65
Cephalosporin Toxicity
``` Fairly safe... Superinfection DISULFIRAM-LIKE RXN Allergy (10% cross sensitivity w/ PCN) GI upset Dose DEPENDENT renal tubular necrosis (Synergistic nephrotoxicity with Aminoglycosides) ```
66
Monobactam Drugs
Aztreonam (parenteral)
67
Aztreonam Spectrum
ONLY Aerobic G- rods! ie. Pseudomonas, Serratia, Klebsiella, Proteus NO ACTIVITY against G+ or anaerobes
68
Aztreonam Adverse Rxns
Few side effects... | Phlebitis, rash, abnormal liver function
69
Aztreonam Use
Good for PCN allergic (no cross sensitivity w/ other beta-lactams)
70
Carbapenem Drugs
Imipenem (IV); Cilastin Meropenem (IV) Ertapenem (IV/IM) "I, ME"
71
What is cilastin?
A dihydropeptidase inhibitor
72
Why is imipenem given with cilastin?
Imipenem is rapidly inactivated by renal tubule dihydropeptidases. Cilastin blocks these. ***Meropenem is NOT inactivated by dihydropeptidases!
73
Imipenem and Meropenem Spectrum
BROAD spectrum including anaerobes, G+ and G- Great for empirical therapy! Stable against beta-lactamases
74
Imipenem and Meropenem Use
Mixed infections | Empirical therapy
75
Imipenem Contraindications
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
Imipenem is DOC for...?
Beta-lactamse producing Enterobacter infections
77
Ertapenem Spectrum
Wide variety of G+, G-, and anaerobic microorganisms, particularly Enterobacteriaceae Highly stable against beta-lactamases Less active against Pseudomonas, should NOT be used!
78
Ertapenem Metabolism
Renal elimination
79
Vancomycin MOA
Prevents transpeptidation of the peptidoglycan chain by binding to the terminal D-ala-D-ala. Bactericidal
80
Vancomycin Resistance
Mutation of the terminal D-ala site
81
Vancomycin Use
``` 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
Vancomycin Spectrum
Only G+
83
Vancomycin Adverse Reactions
Ototoxicity Nephrotoxicity "Red man" Syndrome Thrombophlebitis on IV injection
84
Fosfomycin MOA
Inhibits cell wall synthesis at one of the first steps of peptidoglycan synthesis: Prevents NAG to NAM reduction in cytoplasm
85
Fosfomycin Spectrum
G+ and G- (broad?)
86
Fosfomycin Administration
Oral
87
Fosfomycin Use
Uncomplicated UTI (not the DOC)
88
Fosfomycin is synergistic with what?
Beta-lactam, aminoglycoside, or fluoroquinolone!
89
Fosfomycin Metabolism
Excreted by the kidney
90
Bacitracin MOA
Interferes with final dephosphorylation step in the phospholipid carrier cycle: Can't transfer NAG-NAM across the inner membrane
91
Bacitracin Administration
Typically topical (used in neosporin), rarely parenteral (risk of nephrotoxicity)
92
Bacitracin Spectrum
G+
93
Bacitracin Use
Most commonly used topically to prevent superficial skin and eye infections following minor injuries

Pharmacology Exam 2 (4 decks)

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