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Name the polyene antifungals?
- Amphotericin B deoxycholate-Fungizone cAmB
- Amphotericin B lipid complex-Abelcet (ABLC)
- Liposomal amphotericin B-Ambisone (L-AMB)
- Amphotericin B colloidal dispersion-Amphocil or Amphotec (ABCD)
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What is the MOA of Azoles?
- 14-α-demethylase inhibitors, deplete ergosterol of fungus (and human cholesterol cell membrane
- many CYP450 interactions
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What is the MOA of Amphotericin B?
directly binds ergosterol ⇒ pore formation and leakage of intracellular contents
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List Amphotericin B PK parameters
- Fungicidal
- Concentration-dependent killing (Cmax/MIC)
- Broad-spectrum agent for yeasts and molds
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List the species that AmpB does not cover.
- Aspergillu terreus
- Trichosporon
- Scedosporium and occasionally
- Candida lusitaniae
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List the AmpB AEs
- Severe infusion related reactions
- ⇓ K+ & ⇓ Mg
- Nephrotoxicity
- Anemia
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What medication is given to prevent severe infusion related reactions (the fever, chills, rigors, & anaphylaxis) associated with AmpB?
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The Johnson RC prospective trial showed an advantage for the treatment of what pathogen and with which AmpB formulation ?
- H. capsulatum
- Liposomal (L-AMB)
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List in order AmpB formulations in order from least to most nephrotoxic:
- colloidal dispersion; amphotec, amphocil ABCD
- lipid complex; ablecet ABLC
- liposomal; ambisome L-AMB
- deoxycholate; fungizone cAmB
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Which AmpB formulation has the least Infusion site reactions?
liposomal AmpB; Ambisome L-AmB
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What is the dose for cAmB?
- 0.5-1 mg/kg
- for invasive disease 1-1.5 mg/kg
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What Amp form. has the highest Cmax?
Liposomal AmpB, Ambisome, L-Amb
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Longest t 1/2 for AmpB formulation
lipid complex, Abelcet, ABLC
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What is cAmb % in urine?
3-20% not for UTI unless be given directly
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What is cAmb % in CSF?
0-4 %
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Give the brand name for the Triazoles:
Fluconazole
Itraconazole
voriconazole
posaconazole
- Fluconazole- Diflucan
- Itraconazole- Sporanox
- voriconazole- Vfend
- posaconazole- Noxafil
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Fluconazole covers?
- majority of:
- Candida
- Crytococcus
- Coccidioides
- Does NOT cover molds
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Dosing for L-AMB and ABLC
3-6 mg/kg
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Itraconazole coverage?
- Candida
- Crytococcus
- Coccidioides
- Aspergillus
- Blastomyces & Histoplasma
- Does NOT cover molds
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Voriconazole coverage?
- Aspergillus
- Scedosporium & Fusarium
- resistant Candida sp
- (caution in S-DD isolates) susceptible dose-dependent
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Posaconazole coverage?
- Aspergillus
- Scedosporium & Fusarium
- resistant Candida sp
- Zygomycetes sp
- only azole that covers mucomycoses
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Which azoles have both IV/PO formulations?
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Posaconazole has to be taken with ?
fatty food♨
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Voriconazole has to be taken ?
withOUT food
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What is the sig for Itraconazole solution and capsules? and oral BA?
- solution: take withOUT food; 70-80% BA
- capsules: take with food♨ or acidic drink ☕; 50% BA
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What is the concentration of fluconazole in:
CSF
Urine
Vitreous?
- CSF > 60%
- Urine 90%
- Vitreous 28-75%
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Fluconazole has the half-life?
longest; 31 hours
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Which azole has a BBW?
Itraconazole; CHF/cardiomyopathy, edema, pulmonary, edema HA
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What are the AEs of Voriconazole?
- transient ocular sx (enhanced brightness, blurry vision, color changes, photophobia-25% of pts w/in 60min)
- hallucinations, elevated alkaline phosphatase
- phototoxic: cheilitis, erythema, and occasional blistering
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Which 2 azoles are well tolerated
- fluconazole
- posaconazole
- usually only a HA
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What are the general AEs associated with all azoles?
- GI (N/V/D, epigastric pain)
- rash
- elevated hepatic enzymes
- QT prolongation
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Triazoles are the mostly inhibit which hepatic enzyme? which azoles in particular?
- all but mainly CYP3A4
- itraconazole and posaconazole
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What is the dose of fluconazole?
200-800 mg daily
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What is the dose, level, & target for itraconazole?
- 200mg TID X 3d, then 200 mg BID
- random 2 wks
- 0.5-1.5 mcg/mL
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What is the dose, level, & target for voriconazole?
- 6mg/kg (max 600mg) IV/PO BID X 2 doses, then 4mg/kg IV or 200mg PO BID
- trough 5-7 days
- 2-5.5 mcg/mL
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What is the dose, level, & target for posaconazole?
- 200 mg QID, 400 mg BID
- random 5-7 days
- 0.5- 1.5 mcg/mL
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Name the echinocandins
- Caspofungin (Cansidas)
- Micafungin (Mycamine)
- Anidulafungin (Eraxis)
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Echinocandins are for Candida sp. and for Aspergillus sp.
fungicadal for candida and fungistatic for aspergillus
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Echinocandin AEs
N/V/D and infusion related reactions similar to red man syndrome
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5-FC bone marrow suppression is seen at what level ?
levels > 100 mcg/mL
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