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Infectious Disease > Antifungals > Flashcards

Antifungals Flashcards

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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
Azole MOA
Inhibit fungal CYP450, decreasing ergosterol production
26
Itraconazole good spectrum
``` C. albicans C. tropicalis C. parasilosis C. lusitaniae Cryptococcus neoformans Aspergillus Many dimorphic fungi ```
27
Itraconazole Moderate spectrum
C. glabrata | C. Krusei
28
Itraconazole Poor spectrum
Mucorales (zygomycetes spp.), other moulds
29
Fluconazole Good spectrum
``` C. albicans C. tropicalis C. parasilosis Cryptococcus neoformans Coccidiodes immitis ```
30
Voriconazole Good spectrum
``` C. albicans C. tropicalis C. parasilosis C. lusitaniae C. krusei Aspergillus spp.** Many other moulds ```
31
Fluconazole moderate spectrum
C. glabrata
32
Fluconazole poor spectrum
Moulds Dimorphic fungi C. krusei
33
Voriconazole Moderate spectrum
C. glabrata & C. albicans (that are fluconazole resistant) Fusarium spp.
34
Voriconazole poor spectrum
Mucorales (zygomycetes spp.)
35
Posaconazole good spectrum
``` C. albicans C. tropicalis C. parasilosis C. lusitaniae C. krusei Aspergillus** Mucorales (Zygomycetes spp)*** Many moulds Dimorphic fungi*** ```
36
Posaconazole moderate spectrum
C. glabrata | Fusarium spp.
37
Isavuconazole good spectrum
Candida spp. Aspergillus spp. *** Mucorales (Zygomycetes spp.) Other moulds, dimorphic fungi
38
Isavuconazole moderate spectrum
C. glabrata
39
Isavuconazole poor spectrum
Fusarium
40
Itraconazole AEs
Hepatotoxicity QTc prolongation Contraindicated with HF
41
Itraconazole DDIs
Strong CYP3A4 inhibitor
42
Itraconazole important facts
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
Itraconazole utility
DOC for some dimorphic infxns, such as histoplasmosis
44
Fluconazole AEs
Can cause hepatotoxicity or rash | QTc prolongation
45
Fluconazole DDIs
Lower propensity for drug interactions Strong inhibitor of CYP 2C9 and 2C19 Moderate inhibitor of CYP 3A4
46
Fluconazole Important facts
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
Fluconazole utility
DOC for many susceptible fungal infections
48
Voriconazole AEs
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
Voriconazole important facts
Contraindicated in CrCl < 50 in IV; can use oral | Eliminated hepatically and not useful for treatment of candiduria
50
Utility of Voriconazole
DOC for invasive aspergillosis
51
Posaconazole AEs
Hepatotoxicity, rash GI disturbances QT prolongation
52
Posaconazole DDIs
Strong inhibitor of CYP3A4
53
Posaconazole important facts
Delayed release tablets and oral suspension dosing is not interchangedable Oral: take with food to increase absorption
54
Posaconazole utility
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
Isavuconazole AEs
Hepatotoxicity
56
Isavuconazole DDIs
Substrate of CYP3A4, inhibitor of CYP 4A4, P-gp, and organic cation transporter 2 (OCT 2)
57
Isavuconazole important facts
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
Isavuconazole utility
treatment of invasive mold infections
59
Isavuconazole loading dose regimen
q8h x 48h then q24h
60
Echinocandins MOA
inhibit the synthesis of beta-1,3-glucan, a component of the fungal cell wall
61
Echinocandins
Capsofungin Micafungin Anidulafungin
62
Echinocandin good spectrum
``` C. albicans C. tropicalis C. lusitaniae C. galbrata*** C. krusei*** Aspergillus spp.*** C. parasilosis ```
63
Echinocandin moderate spectrum
Mucorales, in combo with ampho b
64
Echinocandin poor spectrum
Most non-aspergillus moulds | Cryptococcus neoformans
65
Echinocandin AEs
Mild histamine-mediated infusion-related reactions (not common; just slow down infusion rate) Hepatotoxicity (rare)
66
Echinocandin important facts
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
Echinocandin DDIs
Minor | Be cautious when using caspofungin with CsA or rifampin and micafungin with sirolimus
68
Echinocandin utility
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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