PK/PD/Abx Mayo Flashcards
what are the highly bioavailable antimicrobials?
FQ, Fluconazole, voriconazole, metronidazole, linezolid, minocycline, doxycycline, bactrim, rifampin
what is volume of distribution?
size of hypothetical compartment necessary to account for total amount of drug in the body as if it was present in the same concentration found in plasma. =amount of drug in body/measured peak plasma concentration
A high volume of distribution means ??
distribute widely into tissues with low plasma concentration. typically lipophiillic like azithromycin
a low volume of distribution means?
hydrophillic drugs with more blood than tissues.
what are drugs typically hepatic metabolized?
macrolines, clindamycin, chloramphenicol, antifungals, rifampin, PI
what are CYP3A inducers? clinical significance?
rifamycins, anticonvulsant agents - higher doses of concomitant medications needed.
what are the CYP3A inhibitors? clinical significance?
Doses of concomitant medications needs to be decreased. Examples like macrolines, azole antifungals, CCB (diltiazem, verpamil)
what does MIC mean?
lowest concentration that inhibits visible growth in vitro
what is post antibiotic effect?
persistent suppression of bacterial regrowth after antibiotic is removed or levels decrease to below the MIC for the organism
what abx illustrates post antibiotic effect?
typically that act by inhibiting protein/nucleic acid synthesis like macrolines, FQ, aminoglycosides. Beta lactams can do it against gram positive but not gram negative (exception is carbapenems against gram negative)
what are the 3 factors that predictive of antimicrobial efficacy?
- peak concentration to MIC ratio
- AUC/MIC
- T>MIC
Parameters and drugs that exhibit concentration dependent killing?
Peak/MIC ratio; AUC/MIC ratio.
Aminglycosides, FQ, Metronidazole, amphotericin, Echinocandins, daptomycin, colistin
parameters/drugs that exhibit killing without substantial PAE
T>MIC; penicillins, cephalosporins, carbapenems, vancomycin, clindamycin, macrolines, flucytosine
parameters/drugs that exhibit time-dependent killing with moderate/prolonged PAE?
parameters: AUC/MIC, T>MIC; azithromycin, tigecycline, vancomycin, linezolid, tetracyclines, clindamycin, azoles, FQ, strepogramins
what are the toxicities of penicillins?
all has hypersenitivity, GI, and phlebitis with IV therapy. High dose penicillin can cause seizures.
Side effect special to ticarcillin?
hypernatremia, hypokalemia, platelet dysfunction
Important thing to note about Zosyn?
neutroepnia with long term therapy, associated with false positive galactomannin antigen assays (aspergillus)
mechanism of action for penicllins?
bind to penicillin binding proteins of cell wall, inhibiting x linking
toxicities associated with carbapenems?
GI side effects, hypersensitivity reactions, drug fever, and overgrowth of resistnat organisms (yeast, stenotrophomas, C.Diff), seizures
toxicities of aminoglycosides?
reversible nephrotoxicity, irreversible auditory toxicity, A and rarely neurmuscular bloackade
what’s good about minocycline?
active against MRSA for mild disease in patients who cannot tolerate vanc, stenotrophomas, and mycobacterium marinum. Good against intracellular stuff
Mechanism of action of triazoles?
inhibit ergosterol synthesis and cell membrane formation
what’s the general spectrum of activity for fluconazole?
active against many candida species, cryptococcus, coccidiodes immitus. Alternative agent against histo/blasto. Less activity against glabrata, inactive against krusei
general spectrum for itraconazole?
active against some fillamentous fungi (aspergillus, sporothrix, pseudallescheria, alternaria) with similar activity against candida. DOC for histo and blasto
general specturm for voriconazole?
active against fillamentous fungi, active against most strains of candida, coccidiosis, cryptococcus, histo and blasto.
general spectrum for posaconazole?
similar to voriconazole (filamentous, candida, crypto, coccidiosis, histo, blasto) but also add activity against zygomycetes
Toxicities for triazoles?
all eelvate LFTs,prolong QT, Vori - rash + visual disturbances), Itraconazole is a negative inotrope (do not use in CHF)
MOA of polyenes?
amophotericin bind to ergosterol in cell membrane and causes cell damange by increasing permeability and allowing efflux.
spectrum of activity for polyenes?
yeasts, dimorphic fungi, filamentous fungi. less activity against aspergillus terreus, variable activity against aspergilus flavus, zygomycetes, and dematiaceous molds.
toxicity of amphotericin?
infusion related (pre-treat), reversible nephrotoxicity, hypokalemia, hypomagnesemia, anemia,CNS. releases n slowly from peripheral tissues
MOA of echinocandins?
inhibit 1,3b-d-glucan synthesis (cell wall inhibitor)
spectrum of activity of echinocandins?
active against candida species including most azole resistant, aspergillus. Not active against cryptococcus, zygomyctes
