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Infectious Disease > Antifungals > Flashcards

Antifungals Flashcards

1
Q

Yeasts

A

Candida

Cryptococcus

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2
Q

Dimorphic fungi

A

Coccidioides
Blastomyces
Histoplasma
Paracoccidiodes

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3
Q

Moulds

A

Aspergillus
Zygomycetes
Fusarium
Scedosporium

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4
Q

Polyenes

A

Amphotericin B

Topical nystatin

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5
Q

Main toxicity of amphotericin B

A

Nephrotoxicity

Infusion-related Rxns

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6
Q

Ampho. B MOA

A

Polyenes bind to the ergosterol in the cell membrane of fungi, disrupting its membrane

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7
Q

ABCD

A

Ampho. B colloidal dispersion

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8
Q

ABLC

A

Ampho. B lipid complex

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9
Q

LAmB, Ambisome

A

Liposomal amphotericin B

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10
Q

Spectrum for Polyenes

A

Good for everything except candida lusitaniae

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11
Q

Polyene AEs

A

Nephrotoxicity
Infusion-related reactions (use APAP or benadryl)
Electrolyte disturbances (decreased Mg/Ca, increase/decrease K)

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12
Q

Amphotericin dosing problems

A

-Many formulations can lead to dosing confusion

Ampho. B deoxycholate is 0.5-1.5mg/kg/d and lipid formulations are 3-6mg/kg/d

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13
Q

What is given to treat rigors with amphotericin B

A

Meperidine

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14
Q

Utility of Polyenes

A

DOC for cryptococcal meningitis (and serious forms of other fungal infections, such as dimorphic fungi and some mould infections)

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15
Q

Drug interactions with amphotericin

A

Increased nephrotoxicity with other nephrotoxic agents (aminoglycosides, CsA, etc)

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16
Q

Antimetabolits

A

Flucytosine (5-FC) is the only drug in this class

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17
Q

5-FC spectrum

A

in combination with amphotericin B: cryptococcus neoformans, most species of candida

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18
Q

5-FC MOA

A

Antimetabolite that interferes with DNA synthesis; enters fungal cell -> converts to floururacil -> competes with uracil -> interferes with fungal RNA and protein synthesis

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19
Q

5-FC AEs

A

Relatively selective for fungi
Can cause bone marrow suppression, esp in high doses for long periods of time
Can cause GI disturbances and CNS effects (HA, confusion, atacia, hallucinations)

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20
Q

5-FC important facts

A

Drug concentration monitoring usually done off site.
Check peak about 2 hours after a dose is given
Do not rely on concentrations alone
Dose adjustments need for renal insufficiency

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21
Q

Drug interactions for 5-FC

A

Increased effect with amphotericin B

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22
Q

5-FC utility

A

Tx of cryptococcal disease in combo with Ampho. B

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23
Q

5-FC Don’t Forget

A

Follow CBC closely

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24
Q

Azoles

A 
Itraconazole
Fluconazole
Voriconazole
Posaconazole
Isavuconazole
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25
Q

Azole MOA

A

Inhibit fungal CYP450, decreasing ergosterol production

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26
Q

Itraconazole good spectrum

A 
C. albicans
C. tropicalis
C. parasilosis
C. lusitaniae
Cryptococcus neoformans
Aspergillus
Many dimorphic fungi
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27
Q

Itraconazole Moderate spectrum

A

C. glabrata

C. Krusei

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28
Q

Itraconazole Poor spectrum

A

Mucorales (zygomycetes spp.), other moulds

29
Q

Fluconazole Good spectrum

A 
C. albicans
C. tropicalis
C. parasilosis
Cryptococcus neoformans
Coccidiodes immitis
30
Q

Voriconazole Good spectrum

A 
C. albicans
C. tropicalis
C. parasilosis
C. lusitaniae
C. krusei
Aspergillus spp.**
Many other moulds
31
Q

Fluconazole moderate spectrum

A

C. glabrata

32
Q

Fluconazole poor spectrum

A

Moulds
Dimorphic fungi
C. krusei

33
Q

Voriconazole Moderate spectrum

A

C. glabrata & C. albicans (that are fluconazole resistant)
Fusarium spp.

34
Q

Voriconazole poor spectrum

A

Mucorales (zygomycetes spp.)

35
Q

Posaconazole good spectrum

A 
C. albicans
C. tropicalis
C. parasilosis
C. lusitaniae
C. krusei
Aspergillus**
Mucorales (Zygomycetes spp)***
Many moulds
Dimorphic fungi***
36
Q

Posaconazole moderate spectrum

A

C. glabrata

Fusarium spp.

37
Q

Isavuconazole good spectrum

A

Candida spp.
Aspergillus spp. ***
Mucorales (Zygomycetes spp.)
Other moulds, dimorphic fungi

38
Q

Isavuconazole moderate spectrum

A

C. glabrata

39
Q

Isavuconazole poor spectrum

40
Q

Itraconazole AEs

A

Hepatotoxicity
QTc prolongation
Contraindicated with HF

41
Q

Itraconazole DDIs

A

Strong CYP3A4 inhibitor

42
Q

Itraconazole important facts

A

Lower F than the solution and are less preferred for systemic fungal infections
Capsules always be taken with food
Solution taken on empty stomach
Absorption inhibited by PPIs

43
Q

Itraconazole utility

A

DOC for some dimorphic infxns, such as histoplasmosis

44
Q

Fluconazole AEs

A

Can cause hepatotoxicity or rash

QTc prolongation

45
Q

Fluconazole DDIs

A

Lower propensity for drug interactions
Strong inhibitor of CYP 2C9 and 2C19
Moderate inhibitor of CYP 3A4

46
Q

Fluconazole Important facts

A

Adjust dose based on renal function
Poorly active against C. krusei and C. glabrata, it is best to check for susceptibilities and give 800mg/d
High F

47
Q

Fluconazole utility

A

DOC for many susceptible fungal infections

48
Q

Voriconazole AEs

A

Hepatotoxicity, rash, QT prolongation
Visual effects; tend to go away with continued use
Visual and auditory hallucinations
Sun sensitivity
Drug interactions (moderate inhibitor CYP2C9 and CYP 3A4)

49
Q

Voriconazole important facts

A

Contraindicated in CrCl < 50 in IV; can use oral

Eliminated hepatically and not useful for treatment of candiduria

50
Q

Utility of Voriconazole

A

DOC for invasive aspergillosis

51
Q

Posaconazole AEs

A

Hepatotoxicity, rash
GI disturbances
QT prolongation

52
Q

Posaconazole DDIs

A

Strong inhibitor of CYP3A4

53
Q

Posaconazole important facts

A

Delayed release tablets and oral suspension dosing is not interchangedable
Oral: take with food to increase absorption

54
Q

Posaconazole utility

A

PO tabs, suspension and IV: prophylaxis of candida and aspergillus in high risk patients
PO suspension: oropharyngeal candidiasis refractory or ristant to fluconazole/itraconazole

55
Q

Isavuconazole AEs

A

Hepatotoxicity

56
Q

Isavuconazole DDIs

A

Substrate of CYP3A4, inhibitor of CYP 4A4, P-gp, and organic cation transporter 2 (OCT 2)

57
Q

Isavuconazole important facts

A

Supplied as a prodrug
Available as IV injection and PO capsules
Can be taken w/ or w/out food
Very broad spectrum
Very long t1/2; extensive loading dose regimen

58
Q

Isavuconazole utility

A

treatment of invasive mold infections

59
Q

Isavuconazole loading dose regimen

A

q8h x 48h then q24h

60
Q

Echinocandins MOA

A

inhibit the synthesis of beta-1,3-glucan, a component of the fungal cell wall

61
Q

Echinocandins

A

Capsofungin
Micafungin
Anidulafungin

62
Q

Echinocandin good spectrum

A 
C. albicans
C. tropicalis
C. lusitaniae
C. galbrata***
C. krusei***
Aspergillus spp.***
C. parasilosis
63
Q

Echinocandin moderate spectrum

A

Mucorales, in combo with ampho b

64
Q

Echinocandin poor spectrum

A

Most non-aspergillus moulds

Cryptococcus neoformans

65
Q

Echinocandin AEs

A

Mild histamine-mediated infusion-related reactions (not common; just slow down infusion rate)
Hepatotoxicity (rare)

66
Q

Echinocandin important facts

A

No oral formulation yet
Differences among the echinocandins are minor and mostly PK
Capsofungin and micafungin are eliminated by non-CYP450 metabolism
Anidulafungin degrades in the plasma and avoids hepatic metabolism

67
Q

Echinocandin DDIs

A

Minor

Be cautious when using caspofungin with CsA or rifampin and micafungin with sirolimus

68
Q

Echinocandin utility

A

Becoming the DOC for invasive candidiasis
Useful for treatment of invasive aspergillosis but do not have the level of evidence that voriconazole and amphotericin do

Infectious Disease (19 decks)

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