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Antifungal agents Flashcards

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1
Q

Risk factors of fungal infections

A

neutropenia, corticosteroids, TPN, plonged or excessive use, CVLs, mechanical ventilation, CRRT, immunosuppressants

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2
Q

Most commonly encountered fungi

A

candida species: c. albicans, c. glabrata, c. parapsilosis, C. krusei, asperigllus, histoplasmosis (midwest)

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3
Q

Azoles options

A

fluconazole (diflucan), itraconazole (Sporanox), voriconazole (Vfend), posaconazole (noxafil)

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4
Q

Echinocandins options

A

anidulafungin (Eraxis), caspofungin (Cancidas), micafungin (Mycamine)

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5
Q

Imidazole options

A

ketoconazole (Nizoral), clotrimazole, miconazole

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6
Q

Micallaneous options

A

amphotericin B (Fungizone), liposomal amphotericin B, flucytosine (Ancobon), nystatin, terbinafine (Lamisil)

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7
Q

Azole MOA

A

Inhibits synthesis of ergosterol by inhibiting fungal CY450 enzymes, blocked formation of the critical ergosterol component results in a damaged fungal cell membrane and leakage of cytoplasm to inhibit cell growth, fungistatic

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8
Q

difulcan spectrum of activity

A

candida, less against C. glabrata, histoplasma capsulatum, blastomyces dermatitides, coccidioides immitis

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9
Q

what are difulcan not affected against?

A

C. Krusei, aspergillus

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10
Q

PK of difulcan

A

great absorption orally regardless of gastric pH which is unique to this drug, IV/PO, great system wide penetration, excreted unchanged in urine, renal adjustment

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11
Q

Clinical use of difulcan

A

most commonly used antifungal, Candidiasis DOC, oropharyngeal, esophageal, systemic, UTI, fungemia, cryptococcal meningitis

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12
Q

ADR of Difulcan

A

very well tolerated, elevation of LFT, N/V

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13
Q

DI of difulcan

A

worry more about these, HCTZ, warfarin, phenytoin

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14
Q

Dosing of difulcan

A

topical candidiasis- 100-200 mg PO QD, non-invasive candidiasis- 200-400 mg/d, invasic=ve- push the dose- 400-800 mg/d

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15
Q

itraconazole MOA

A

inhibits ergosterol synthesis, fungistatic

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16
Q

Spectrum of activity of itraconazole

A

asperigillus, candida, cryptococcus neoformans, histoplasma capsulatum, blastomyces dermatitidis

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17
Q

clinical use of itraconazole

A

reserved for more rare fungal infections, blastomycosis, histoplasmosis, life-threatening infxn, aspergillosis, onchomycosis of finger and toes, esophageal/oropharyngeal

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18
Q

Voriconazole MOA

A

inhibits ergosterol synthesis, fungistatic

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19
Q

Voriconazole spectrum

A

aspergillus, including amphotericin resistant, all candida, cryptococcus neoformans

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20
Q

Voriconazole kinetics

A

IV/PO, great Vd, not nephrotoxic but vehicle it is compounded to is, IV contraindicated in

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21
Q

DI of voriconazole

A

lots, has activity of most cyp 450 enzymes, major limitation but still used when needed

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22
Q

Voriconazole clinical uses

A

invasive aspergillosis, pt usually get dual therapy and voriconazole, other serious fungal infxns, drug resistant candidiasis

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23
Q

Posaconazole (noxafil) MOA

A

inhibits ergosterol synthesis, fungistatic, similar to itraconazole, only available as a liquid

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24
Q

Spectrum of activity of posaconazole

A

aspergillus, candida, cryptococcus neoformans, very broad

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25
posaconazole clinical use
long term as prophylaxis for aspergillosis in immunocompromised, must take with food
26
Ketoconazole moa
inhibits synthesis ergosterol, blocks formation of ergosterol damages fungal cell membrane and destroys structural integrity, fungistatic
27
Spectrum of ketoconazole
candida albicans, histoplasmosis capsu latum, cryptococcus neoformans, dermatophytes
28
PK of ketoconazole
PO, well absorbed but inversely related to gastric pH, don't use with H2 blockers
29
Clinical use of ketoconazole
only for more rare conditions, chronic mucocutaneous candidiasis, histoplasmosis, blastomycosis
30
ADR of ketoconazole
very hepatotoxic, inhibits adrenal steroids and testosterone synthesis leads to gynecomastia, dec libido, alopecia
31
DI of ketoconazole
so many!!!
32
Clotrimazole options
Lotrimin, lotrimin AF, lotrisone (clotrimazole+betamethasone)
33
MOA of clotrimazole
binds phospholipids in fungal cell wall, alters cell wall permeability results in loss of essential intracellular components
34
Spectrum of clotrimazole
candida, limited in others
35
Clinical use of clotrimazole
use topically, available OTC, dermatophytosis candidiasis- topical, vulvovaginal candidiasis- topical, dermatologic infxn, topical
36
Miconazole options
vagistat, lotrimin af, many others
37
Miconazole MOA
inhibits synthesis of ergosterol
38
Spectrum of miconazole
candida
39
Clinical use of miconazole
tinea corposis, tinea pedis, vulvovaginal candidiasis
40
Echinocandins MOA
inhibits synthesis of an integral component of fungal cell wall, fungicidal vs candida, fungistatic vs aspergillus
41
Spectrum of activity of echinocandins
aspergillus, candida, great for C. Glabrata (DOC!)
42
echinocandins has limited activity against
histo, crypto, mucor
43
Echinocandins kinetics
IV, poor urine conc, no renal adjust required
44
ADR of echinocandins
well tolerated, some gi, some histamine rash
45
Echinocandins clinical use
candidiemia, severe esophageal candidiasis, invasive aspergillosis- not monotherapy
46
Amphotericin B MOA
binds to ergosterol, disrupts cell membrane which increases permeability and causes leakage of Na/K, metabolic cell death
47
Spectrum of amphotericin B
candida, cryptococcus neoformans, aspergillus, blastomyces dermatitidis, histoplasma capsulatum, mucor, coccidioides immitis
48
Pk/Pd
IV only, zero penetration into the CNS
49
ADRs of amphotericin B
lots of infusion related ADRs, HA, fever, chills, arthralgias, myalgias, N/V, hoTN, thrombophlebitis, also nephrotoxic, hypokalemia, hypomagnesemia (give K/Mg prophylaxis)
50
Uses of amphotericin B
requires a test of tolerance, histoplasmosis, cryptococcosis, aspergillosis, disseminated candidiasis, empiric therapy in immunocompromised
51
Liposomal amphotericin B pearls
better tolerated from ADR, able to treat CNS infxn, $$$
52
Flucytosine (Ancobon) MOA
incorporated into fungal RNA to interfere w/ protein synthesis
53
Spectrum of flucytosine (Ancobon)
cryptococcus neoformans, candida
54
ADRs of flucytosine
Gi, bone marrow suppression
55
Flucytosine uses
fes, usually combo w/ ampho B, crypto meningitis, invasive pulmonary cryptococcosis
56
Terbinafine (Lamisil), MOA
Inhibits squalene epoxidase, key enzyme in fungal sterol synthesis, used as systemic therapy
57
Clinical use terbinafine
onchomycosis (finger and toe), tinea capitis
58
Nystatin MOA
Binds to sterol in fungal cell membrane drastically changing permeability
59
Nystatin availability
PO suspension, powder, tablet, cream
60
Nystatin use
cutaneous and mucocutaneous infxn
61
Nystatin spectrum
candida
62
candidemia tx in non-neutropenic pts
fluconazole is DOC, alternative- LFAmB, AmB, voriconazole, remove lines where appropriate, treat 14 days after first neg culture
63
tx of candidemia in neutropenic pts
consider fungal infxn after 4 days of fever despite broad spectrum abx, initiate tx w/ LFAmB, voriconazole or schinocandin, fluconazole is only to be used if pts is not critically ill nad no recent exposure to azole antifungal agents
64
TX of UTI caused by candida
asymptomatic cystitis- no tx, symptomatic cystitis- fluconazole- DOC amB if resistant, pyelonephritis- fluconazole
65
TX of CNS candidiasis
LFAmB followed by fluconazole daily, tx continues until clinical improvement is evident
66
Candida isolated from respiratory secretions
tx not recommended, candida rarely causes LRTI, mostly seen in immunocompromized, neutropenic pts
67
Invasive pulmonary aspergillosis
voriconazole -DOC, alternative- LFAmB, salvage therapy- posaconazole, echinocandin, LFAmB, measure to improve clinical response- reduce immunosuppression- steroids, neurtopenia- surgery, duration 6-12 wk

Pharmacology (61 decks)

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