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Difference immunocompromised pt and imunosuppressed?
IC: Having an impaired immune system, IS: Your immune system is suppressed by drug or radiation
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Whats the standard of tx for a hematologic cancer?
HSCT
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Where do they harvest stem cells?
Marrow, peripheral blood, cord blood p60
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2 types of marrow transplant?
Autologous and allogenic, auto = automatic, stem cells are exact match, usually from pt. Allo as close as possible to find. P.63
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Most common type of HSCT?
Auto p.63
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Nephrotoxicity?
Poisonous effect or destruction of kidney cells, serum creatinin. P.
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Importance of nephrotoxicity to patient?
Can reduce bodys ability to clear blood of toxins, make have to DC AmB-d or Abelcet,limiting or complicating other med regimens, dialysis if severe
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Drugs can be metabolized by?
Kidney or liver
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Inducer?
Reduces blood levels of other drug
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Inhibitor?
Increases blood level of other drug
- Importance of inducers/inhibitors?
- Because immunosuppressant drugs have narrow therapeutic threshold.
- Risk fxs for invasive fungal inf?
- ABs, steroids, ICU stay, neutropenia, diseases (leukemia, lymphpoma, AIDS), central or peripheral intravenous catheters, immunosuppressants, surgery, extensive burns, chemotherapy, p101
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Most common strand of yeast in humans?
Candida Albicans p103
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Is cryptococcus a yeast or mold?
Yeast
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Zygomycetes and aspergillus, yeast or mold?
Mold p104
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Most common entry point for aspergillus?
Lungs
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What is empiric therapy?
Broad spectrum therapy without knowing species
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Ind for myca?
Must have identified candida inf. pts w/ candidemia, acute disseminated candidiasis, candida peritonitis and abscesses; esophageal candidiasis; prophylaxis for candida inf in pts undergoing HSCT P 133
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How many echinos?
3, myca, cancidas, eraxis
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What is the philosophy of antifungal stewardship?
Right drug, right pt, right dose, right time. P.8
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Where do the echinos target activity?
Fungal cell wall.
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Why important that echinos target that area?
Humans dont have cell walls, lower aes.
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Are echinos fungicidal or static?
Cidal, except Cancidas w/ aspergillus is static
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State what makes each drug different
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Caspo messaging?
H2H data, no loading, no refrig, Pyxis reduce hang time, minibagplus.
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Eraxis messaging?
No loading dose, refrig, Pyxis, no head to head, no ped ind, drug interaction studies p13.
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Indications, Caspo vs Myca?
Caspo has empiric, myca is treatment.
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Aspergillus indication with Caspo?
Ambisome, static activity with echinocandins. Cancidas refractory only. P14.
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Why no loading dose w/ Myca?
Reaches therapeutic levels w/i 2hrs and maintains for 24 hour dosing cycle
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Why is the d2d w/ cyclosporine an important issue?
Immunosuppressed, changes drug levels. Ask about who makes those changes when pt leaves hosp setting.Who makes sure dose is readjusted when pt clear? Can lead to rejection. P15.
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Eraxis
no data doesnt mean no d2d interactions?
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Is there renal adj with Eraxis?
No
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Loading dose w/ Eraxis?
Yes
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Infusion time for Eraxis?
- 3hrs loading, 90 minutes daily dose p17
- Tie value into panel questions
what does it mean to hcp, pt, hosp?
- More time on pump, cant run another drug at the same time, requires dedicated line, timing of medication important, may delay other drugs dosed. P19
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Why is Pyxis important? p20
Hang time, Refrig space, Pt movement/discharge
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Azoles cidal or static candida?
Static
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3 azoles?
Fluconazole, Voriconazole, Posiconazole
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Largest challenge with Posi?
Oral suspension w/ high fat meal
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Where do azoles target?
Cytoplasm
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Most common azole?
Fluconazole
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Why azoles?
Safe, cheap, effective
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Md using fluconazole. What would you say?
Shifting etiology, Lack of coverage for non-albicans p24 and 25
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Vori: Formulations?
Oral and IV, susp
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Is it an advantage that Vori has a broader spectrum of activity than Myca?
- Could be, but risk of those species is low, could lead to cross resistance. IDSA says dont use azole if prior azole exposure. IDSA says must switch classes, not just meds. IDSA doesnt define recent P27
- Could tie in readmittance and Medicare not paying.
- If on fluconazole for prophylaxis, must change
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Max does of Myca?
896mg, did not see increase in toxicity
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Posi advantage?
Zygomycetes p30
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Where do the polynes target activities on the fungal cell?
Membranes, more toxic to human cells because can target human cells
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Ampho B advantages?
No resistance, Cidal/effective, Cheap
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Ampho B Disadvantages?
Nephrotoxicity, Toxic to human cells, cell membrane p36
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2 major saftety challenges with deoxy?
- Nephrotoxcitity
- Inf related rxs
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Abelcet same amount of data as Ambisome?
Not even close
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What does data between Abelcet and AmBisome show?
Less nephrotoxicity, Less irr, Lead to less dcs
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Perceived advantage of Abelcet over deoxy
Less nephrotox
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Is there h2h data deoxy v Ambisome?
Safety and efficacy data showed less nephrotoxicity, comparable efficacy
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What drug is killing fungus in AmBisome?
Amphotericin B p40/41
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