PK-PD 101
Bioavailability
Distribution
Pharmacodynamic relationships
Distribution 2
100
This pharmacokinetic concept refers to the proportion of administered drug that reaches the systemic circulation.
What is bioavailability?
100
This azole antifungal is 96% bioavailable, allowing for 1 to 1 conversion of doses when switching from IV to oral.
What is voriconazole?
100
Leaky capillaries and increased protein binding during sepsis result in this alteration of volume status.
What is increased volume of distribution (and risk for suboptimal antibiotic concentrations)?
100
An AUC to MIC ratio of 400 has been associated with optimal patient outcomes for this bug-drug combination.
What are MRSA and vancomycin?
100
These are limitations of the available pharmacokinetic literature on bone penetration (multiple answers possible).
What are non-infected population, single point pharmacokinetics to determine bone to serum ratio, don't always account for heterogeneous nature of bone, etc?
200
This pharmacodynamic concept refers to antibiotics that have optimal bacterial kill as the drug concentration increases. It generally correlates with peak to MIC ratio.
What is concentration dependent killing?
200
This antibiotic is ~80% bioavailable. Therefore, doses are increased by 20% when therapy is switched from IV to oral. Just beware chelation interactions!
What is ciprofloxacin?
200
True or false. Charged antibiotics are MORE likely to have good penetration into the cerebrospinal fluid.
What is false?
200
This drug class requires an AUC to MIC ratio of approximately 30 for optimal kill vs. S. pneumoniae and 125 for P. aeruginosa.
What are the fluoroquinolones?
200
This type of antibiotic generally has a bone and CSF penetration ratio of less than 30% (compared to serum).
What are beta-lactams?
300
This pharmacodynamic concept refers to a drug that has greater antibacterial activity with longer durations of exposure (e.g. time over MIC).
What is time-dependent kill?
300
Although this agent is only ~40% bioavailable when administered by mouth, it achieves robust, prolonged intracellular concentrations.Therefore, oral therapy is generally accepted to be just as effective as IV.
What is azithromycin?
300
True or false. Antibiotics with lower molecular weight and lower protein binding are MORE likely to penetrate the cerebrospinal fluid.
What is true?
300
The correlation between vancomycin troughs and AUC is imperfect. Recent data suggests that approximately 60% of patients will achieve a target AUC of 400 when vancomycin troughs are in this range.
What is LESS than 15 mcg/ml? Neely et al. AAC 2014.
300
This class of antibiotics has more studies for the treatment of chronic osteomyelitis studies than all other classes combined. They also have an average bone to serum ratio of ~50%.
What are fluoroquinolones?
400
This drug/class has > 90% bioavailability (multiple answers).
What are metronidazole, clindamycin, linezolid, azoles,...?
400
Thank goodness this antibiotic is 90 to 100% bioavailable! IV therapy is challenging! It has very short stability (infuse within 4 hours), requires high volumes of D5W for administration, and precipitates if not properly diluted.
What is TMP/SMX?
400
True or false. Ceftriaxone and meropenem have low affinity for active efflux transporters (like Oat-3, P-gp) that are present at the blood brain barrier.
What is true?
400
This is the percentage of time over the MIC that is associated with optimal outcomes of carbapenem therapy.
What is at least 40% (some data suggests 50%)?
400
This MSSA active cephalosporin should never be used systemically for meningitis. It has poor CSF concentrations, partly because it's a good substrate for active transporters at the blood brain barrier.
What is cefazolin?
500
The oral bioavailability of this class of antibiotics is reduced by approximately 50 to 75% when administered with divalent cations.
What are fluoroquinolones?
500
This is an antimicrobial that can be automatically switched from IV to oral by HFHS pharmacists when specific criteria are met (multiple answers).
What are azithromycin, clindamycin, ciprofloxacin, doxycycline, fluconazole, linezolid, metronidazole, moxifloxacin, and voriconazole?
500
This is one potential way to improve the distribution of a beta-lactam into the bone (multiple answers possible).
What is increase the dose, administer more frequently or as a continuous infusion?
500
High peak extended interval dosing is suggested as the default method for pharmacy dosing of aminoglycosides to take advantage of this pharmacodynamic characteristic.
What is concentration dependent killing?
500
Zwitterionic carbapenems have a net neutral charge. This characteristic allows more easy diffusion through the outer wall of Gram-negative bacteria, and also results in favorable CSF penetration. Name a zwitterionic carbapenem (multiple answers).
What are imipenem and meropenem?
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