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30 Cards in this Set
- Front
- Back
Two general classes of Abios |
Cell Wall agents Ribosomal Agents |
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Two types of Cell Wall agents |
β-Lactams Polypeptides |
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Types of β-lactams |
Penam/em Clavam/em Carbapenam/em Cepham/em |
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Gram (+) characteristics |
1.Outer surface teichoic acids 2. High % peptidoglycan 3. Very rigid 4. Limited amt AA and sugars 5. HIGH internal osmolarity |
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Gram (-) characteristics |
1. Surface is LPS 2. Low % peptidoglycan 3. Surface porin channels 4. Cell wall less rigid 5. Low internal osmolarity |
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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. |
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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. |
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Cell Wall Agents are optimally for what Gram stain? |
Gram(+) because of peptidoglycan on the outside and a high internal osmolarity |
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What drug class uses steric hindrance to confer β-Lactamase stability? |
Methicillin (oxacillin) |
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What is the downside of steric hindrance to provide β-lactamase stability? |
It blocks the MOA site. |
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Another hurdle to β-lactam's is they are chemically unstable. What environment inactivates them? |
Acid/water (our stomach environment). This prevents oral dosing. |
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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 |
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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 |
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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) |
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Ampicillin Class |
CWA Penam Broad Spectrum (α-ionizable grp = -NH3+) β-lactamase sensitive Prodrug Ex. Amoxicillin, Ampicillin |
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Carbenicillin Class |
CWA Penam Broad Spectrum (α-ionizable grp = -COO-) (including Pseudomonas) β-lactamase sensitive Ex. Ticarcillin |
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Mezlocillin Class |
CWA Penam Broad Spectrum (α-ionizable grp = -NH3+) Urea in MOA β-lactamase sensitive Ex. Piperacillin |
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Methicillin Class |
CWA Penam Narrow spectrum = G(+) First class to get β-lactamase stability (sterics) Ex. Oxacillin |
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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 |
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Monobactam |
CWA Narrow Spectrum = G(-) (SO3-) *Missing 2nd ring β-lactamase stable (steric bulk and methyl grp prevents binding) Ex. Aztreonam |
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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 |
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What class has a 6-membered ring? |
Cephalosporins CWA's |
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Ways CWA's are stable to β-lactamase? |
1. Steric bulk (methicillin) 2. Trans orientation of H's (carbapenems) 3. -OCH3 (cephalosporins) |
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1st Generation Cephalosporins |
Do NOT enter CNS Narrow Spectrum = G(+) cocci Ex. Cephalexin (PO) |
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2nd Generation Cephalosporins |
Do NOT enter CNS Broader Spectrum = Better G(-) activity Slightly better PO NOT active against pseudomonas Ex. Loracarbef |
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3rd Generation Cephalosporins |
Good for CNS infection Broad Spectrum = G(-) Used for Neisseria gonorrhorae and others ACTIVE against Pseudomonas Ex. Ceftriaxone (IM), Cefdinir (PO) |
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4th Generation Cephalosporins |
Broadest Spectrum = G(-) Quaternary N-ring aids penetration to G(-) Ex. Cefepime |
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All β-lactams are... Bacteriostatic or Bactericidal |
Bactericidal |
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1st-4th Generation Cephalosporins Overall trend? |
Overall trend is broader coverage from 1st-4th generation |
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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. |