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30 Cards in this Set

  • Front
  • Back

Two general classes of Abios

Cell Wall agents




Ribosomal Agents

Two types of Cell Wall agents

β-Lactams




Polypeptides

Types of β-lactams

Penam/em
Clavam/em
Carbapenam/em
Cepham/em

Penam/em


Clavam/em


Carbapenam/em


Cepham/em

Gram (+) characteristics

1.Outer surface teichoic acids


2. High % peptidoglycan


3. Very rigid


4. Limited amt AA and sugars


5. HIGH internal osmolarity

Gram (-) characteristics

1. Surface is LPS


2. Low % peptidoglycan


3. Surface porin channels


4. Cell wall less rigid


5. Low internal osmolarity

What does Cell Wall Trans Peptidase/Penicillin Biding Protein normally do?

PBP normally binds the D-Ala/D-Ala tail of NAM cross link the NAM's of the NAM/NAG


peptidoglycan cell wall.

What is the MOA of β-Lactams?

β-Lactams mimics the D-Ala/D-Ala that the CWT/PBP normally binds. Therefore, it


competes for this reaction and when it is bound, the lactam springs open irreversibly. This prevents cross-linking of the cell wall, weakening it.

Cell Wall Agents are optimally for what Gram stain?

Gram(+) because of peptidoglycan on the outside and a high internal osmolarity

What drug class uses steric hindrance to confer β-Lactamase stability?



Methicillin (oxacillin)

What is the downside of steric hindrance to provide β-lactamase stability?

It blocks the MOA site.

Another hurdle to β-lactam's is they are


chemically unstable. What environment inactivates them?

Acid/water (our stomach environment).




This prevents oral dosing.

How to make β-lactam more acid stable?

Improve acid stability by putting EWG's on the R-grp of the amide to pull electrons from attacking.




This increases acid stability --> PO dose possible

How to extend the spectrum of activity of


β-lactam drugs?




examples?

Alpha-ionizable groups on the R-group provide a charge that changes the permeability of the LPS to allow entry into the peptidoglycan layer.




Ex. Ampicillin, Carbenicillin, Mezlocillin

Penicillin Class

Cell Wall Agent (CWA)


Penam


Narrow spectrum - G(+) cocci


β-lactamase sensitive


Pen-G (Effective, cheap, resistance common)


Pen-V (More stable to acidic environment)



Ampicillin Class

CWA


Penam


Broad Spectrum (α-ionizable grp = -NH3+)


β-lactamase sensitive


Prodrug


Ex. Amoxicillin, Ampicillin

Carbenicillin Class

CWA


Penam


Broad Spectrum (α-ionizable grp = -COO-)


(including Pseudomonas)


β-lactamase sensitive


Ex. Ticarcillin





Mezlocillin Class

CWA


Penam


Broad Spectrum (α-ionizable grp = -NH3+)


Urea in MOA


β-lactamase sensitive


Ex. Piperacillin

Methicillin Class

CWA


Penam


Narrow spectrum = G(+)


First class to get β-lactamase stability (sterics)


Ex. Oxacillin



Carbapenems

CWA


C replaces S on second ring


Broad spectrum (Reactive C, NOT an α-ionizble)


Stable to β-lactamase (Trans sterochem of H's at α position)


Ex. Meropenem (-CH3 eliminates need for


Cilastatin, DHP-1)


Administered IV

Monobactam

CWA


Narrow Spectrum = G(-) (SO3-)


*Missing 2nd ring


β-lactamase stable (steric bulk and methyl grp prevents binding)


Ex. Aztreonam

β-Lactamase inhibitors

Irreversible inhibitor of β-Lactamase


No antibacterial activity


Must be combined with various penicillins


Ex. Clavulanic acid (augmentin)


β-lactamase preferably attacks bc looks like D-Ala/Ala but so wide open

What class has a 6-membered ring?

Cephalosporins




CWA's



Ways CWA's are stable to β-lactamase?

1. Steric bulk (methicillin)


2. Trans orientation of H's (carbapenems)


3. -OCH3 (cephalosporins)

1st Generation Cephalosporins

Do NOT enter CNS


Narrow Spectrum = G(+) cocci


Ex. Cephalexin (PO)

2nd Generation Cephalosporins

Do NOT enter CNS


Broader Spectrum = Better G(-) activity


Slightly better PO


NOT active against pseudomonas


Ex. Loracarbef

3rd Generation Cephalosporins

Good for CNS infection


Broad Spectrum = G(-)


Used for Neisseria gonorrhorae and others


ACTIVE against Pseudomonas


Ex. Ceftriaxone (IM), Cefdinir (PO)

4th Generation Cephalosporins

Broadest Spectrum = G(-)


Quaternary N-ring aids penetration to G(-)


Ex. Cefepime

All β-lactams are...




Bacteriostatic or Bactericidal

Bactericidal

1st-4th Generation Cephalosporins




Overall trend?

Overall trend is broader coverage from 1st-4th generation

Why do β-Lactams work?

Mimic D-Ala/Ala, strained ring, hetero atom bond with electrophilic carbonyl that can be attacked by a nucleophile and once opened, it is irreversible.