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Phar 761 > Antifunals > Flashcards

Antifunals Flashcards

1
Q

Amphotericin B Mechanism

A

Binds ergosterol - disrupts wall function and creates small pores.

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2
Q

Echinocandin Mechanism

A

Inhibits B-(1,3)-glucan synthase

  • Responsible for cross-linking
  • Required for cell wall synthesis
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3
Q

Azole Mechanism

A

Inhibits Cytochrome P450 lanosterol 14-a demethylase

- Required for ergosterol biosynthesis

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4
Q

Amphotericin B Toxicities

A

“Shake and bake”
Nephrotoxicity
- Renal artery vasoconstriction
- Binds to renal tissues

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5
Q

Advantages of LFAB ( FWAB or Bacontericin B)

A

Delays delivery to kidney due to lipophilicity.

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6
Q

Agents - Cidal or static?

A

Ampho - cidal
Azole - static
Echino - cidal against Candida

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7
Q

Major drug interaction with Azoles

A

They inhibit CYP enzymes - 3A4!

Also, PGP

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8
Q

Low end of Fluconazole dose

A

6-12 mg/kg/day in the ICU

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9
Q

Fluconazole Strengths

A

C. albicans

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10
Q

Fluconazole weaknesses

A

Does not cover molds

Often under dosed

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11
Q

Voriconazole strengths

A

Broad spectrum

  • Candida
  • Aspergillus *
  • NOT Mucorales or Zygomycetes

IV and PO
Generic

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12
Q

Gold standard for Aspergillus

A

Voriconazole

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13
Q

Voriconazole weaknesses

A 
Metabolite and cancer risk
Dosing strategy concerns
Toxicities
- LFT increases
- Hallucinations
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14
Q

Posaconazole strengths

A

Broadest spectrum

  • Candida
  • Aspergillus
  • Zygomycetes

IV and delayed release tablet have reliable PK
- QD as oral

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15
Q

Posaconazole weaknesses

A

Very expensive

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16
Q

Isavuconazole (Cresemba) strengths

A

Decent spectrum

  • Aspergillus
  • Mucorales (limited data)
  • NO CANDIDA

IV and oral

  • QD as oral
  • IV : no cyclodextrin (accum. in renal failure)
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17
Q

Isavuconazole weaknesses

A

No prophylaxis data

Very long t1/2 - IV needs loading dose

18
Q

“Advanced” Azole Indications

A

Voriconazole - TREATMENT of IA and IC
Posaconazole - PROPHYLAXIS in high risk patients
Isavuconazole - TREATMENT of IA & Mucormycosis

19
Q

Echinocandins include

A

“Whatever-a-fungin”

20
Q

Echinocandin strengths

A 
Potent against Candida (cidal)
Really well tolerated
Great PK
Few interactions
No cross-resistance with Azoles
21
Q

Echinocandin weaknesses

A 
Limited spectrum: Candida >>> Aspergillus (combo)
- That's about it.
- Not C. neoformans
No oral form
High cost
22
Q

Flucytosine (5-FC)

A

Think Cryptococcal meningitis

23
Q

Terbinafine

A

Toe nails

24
Q

Greatest risk for Invasive Candidiasis

A

GI-Perforation
Also being in the ICU > 3 days
- Really when you have something put inside you.

25
Q

Increasingly prevalent Candida species resistant to fluconazole:

A

C. glabrata

26
Q

Candida species completely resistant to fluconazole:

A

C. krusei

27
Q

What to use for C. krusei

A

Echinocandins: Whatever-a-fungin

Maybe Vori or Posa

28
Q

Only candida species with resistance to Echinocandins

A

C. parapsilosis

29
Q

What to use for C. glabrata

A

Echinocandinds: Whatever-a-fungin IF resistant to Fluconazole.
- If resistant to one azole, resistant to all azoles.

30
Q

Two Candida species that don’t show resistance yet:

A

C. albicans and C. tropicalis

31
Q

Poor prognosis in Candidemia

A

Older age
APACHE > 2
Immunosuppressive therapy
C. tropicalis infection (seems weird)

32
Q

Predictors of good outcome from study:

A

Removal of central venous catheter

Treatment with echinocandin

33
Q

Initial treatment recommendation for Candidemia in non-neutropenic adults:

A

Echinocandin 1st line
or
Fluconazole 800mg followed by 400mg

34
Q

What’s the deal with Candida auris?

A

It causes severe illness.
It can be resistant to all three antifungal options.
It is increasing in prevalence.
It is difficult to identify.
It is showing up in hospitals and nursing homes.

35
Q

When would you worry about IFI (Aspergillosis)

A

Severyly immunocomprimised; bone marrow/blood cancer.

36
Q

Common species involved in IFI

A

A. fumigatus

A. flavus

37
Q

Where do you see IFI show up?

A

Lung and sinuses mostly

CNS most common secondary site

38
Q

Treatment for IFI

A

Voriconazole

  • isavu and posa probably work too
  • addition of Echinocandin may be seen in future
  • Isavu less SE’s

Alternative: Lipid-AmpB

39
Q

What do you do if someone gets a mold infection while on an Azole

A

Ampho

40
Q

Prophylaxis for IA

A

Posa > Vori > micafungin

41
Q

Therapeutic drug monitoring for Voriconazole:

A

Stay above: 2

Stay below: 5-6

Phar 761 (5 decks)

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