PK

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Author:
ch.tyrrell
ID:
150676
Filename:
PK
Updated:
2012-04-28 11:52:53
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Antibiotics Lecture
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Antibiotics
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  1. What is post-antibiotic effect?
    The continued suppression of bacterial growth after a short exposure to antimicrobial agents.
  2. What is concentration-dependent killing?
    • The amount of microbial killing depends on maximum concentration of drug above the MIC.
    • PK/PD Parameters: Peak/MIC
    • Ex: aminoglycosides, FQ, daptomycin, metronidazole
  3. What is time-dependent killing?
    • Amount of microbial killing depends on the time the drug stays above the MIC.
    • PK/PD Parameters: T > MIC
    • Ex: beta-lactams, macrolides, linezolid, vancomyin, clindamycin
  4. Determine the pattern of activity, the goal of therapy and the PK/PD parameter of beta-lactams and linezolid.
    • Pattern of activity: Time dependend and minimal PAE
    • Goal of therapy: Maximize duration of exposure
    • PK/PD parameter: T > MIC
  5. Determine the pattern of activity, the goal of therapy and the PK/PD parameter of vancomycin.
    • Pattern of activity: Time-dependent and minimal PAE
    • Goal of therapy: Maximize amount of drug
    • PK/PD parameter: 24h-AUC/MIC
  6. Determine the pattern of activity, the goal of therapy and the PK/PD parameter of azithromycin and clindamycin.
    • Pattern of activity: Time-dependent and moderate to prolonged PAE
    • Goal of therapy: Maximize amount of drug
    • PK/PD parameter: 24h-AUC/MIC
  7. Determine the pattern of activity, the goal of therapy and the PK/PD parameter of aminoglycosides, daptomycin and FQs.
    • Pattern of activity: Concentration-dependent and prolonged PAE
    • Goal of therapy: Maximize concentration
    • PK/PD parameter: Peak/MIC
  8. What is fT > MIC?
    The amount of time the free or non-protein bound drug concentration exceeds the MIC
  9. What are the near-maximal bactericidal effects when free drug concentration exceeds MIC for cephalosporins, penicillins and carbapenems?
    • 60-70% of dosing interval for cephalosporins
    • 50% of dosing interval for penicillins
    • 40% of dosing interval for carbapenems
  10. What are the advantages to using extended infusions?
    • 1. superior pharmacodynamic profile (more fT > MIC)
    • 2. allows for time between doses for administration of drugs through the same IV line
    • 3. cost savings
  11. List 5 reasons to use antibiotic drug combinations.
    • 1. broad-spectrum empiric thereapy
    • 2. polymicrobial infections
    • 3. decrease resistance
    • 4. decrease dose-related toxicity
    • 5. increase inhibition or killing
  12. Define synergism.
    significanly enhanced inhibition or killing than either drug individually
  13. List 3 mechanisms of synergistic action and provide an example of each.
    • 1. Blockade of sequential steps in a metabolic sequence ex: Bactrim
    • 2. Inhibition of enymatic inactivation ex: Augmentin
    • 3. Enhancement of antibiotic uptake ex: Gentamicin + a penicillin
  14. Define antagonism.
    decreased inhibition or killing than either drug individually
  15. List 2 mechanisms of antagonistic action and give an example of each.
    • 1. Inhibition of cidal activity by static agents ex: linezolid + vancomycin (TCN + PCN)
    • 2. Induction of enzymatic inactivation ex: imipenem + cefoxitin

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