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Pharmacology > Antifungal agents > Flashcards

Antifungal agents Flashcards

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
Q

posaconazole clinical use

A

long term as prophylaxis for aspergillosis in immunocompromised, must take with food

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26
Q

Ketoconazole moa

A

inhibits synthesis ergosterol, blocks formation of ergosterol damages fungal cell membrane and destroys structural integrity, fungistatic

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27
Q

Spectrum of ketoconazole

A

candida albicans, histoplasmosis capsu latum, cryptococcus neoformans, dermatophytes

28
Q

PK of ketoconazole

A

PO, well absorbed but inversely related to gastric pH, don’t use with H2 blockers

29
Q

Clinical use of ketoconazole

A

only for more rare conditions, chronic mucocutaneous candidiasis, histoplasmosis, blastomycosis

30
Q

ADR of ketoconazole

A

very hepatotoxic, inhibits adrenal steroids and testosterone synthesis leads to gynecomastia, dec libido, alopecia

31
Q

DI of ketoconazole

A

so many!!!

32
Q

Clotrimazole options

A

Lotrimin, lotrimin AF, lotrisone (clotrimazole+betamethasone)

33
Q

MOA of clotrimazole

A

binds phospholipids in fungal cell wall, alters cell wall permeability results in loss of essential intracellular components

34
Q

Spectrum of clotrimazole

A

candida, limited in others

35
Q

Clinical use of clotrimazole

A

use topically, available OTC, dermatophytosis candidiasis- topical, vulvovaginal candidiasis- topical, dermatologic infxn, topical

36
Q

Miconazole options

A

vagistat, lotrimin af, many others

37
Q

Miconazole MOA

A

inhibits synthesis of ergosterol

38
Q

Spectrum of miconazole

A

candida

39
Q

Clinical use of miconazole

A

tinea corposis, tinea pedis, vulvovaginal candidiasis

40
Q

Echinocandins MOA

A

inhibits synthesis of an integral component of fungal cell wall, fungicidal vs candida, fungistatic vs aspergillus

41
Q

Spectrum of activity of echinocandins

A

aspergillus, candida, great for C. Glabrata (DOC!)

42
Q

echinocandins has limited activity against

A

histo, crypto, mucor

43
Q

Echinocandins kinetics

A

IV, poor urine conc, no renal adjust required

44
Q

ADR of echinocandins

A

well tolerated, some gi, some histamine rash

45
Q

Echinocandins clinical use

A

candidiemia, severe esophageal candidiasis, invasive aspergillosis- not monotherapy

46
Q

Amphotericin B MOA

A

binds to ergosterol, disrupts cell membrane which increases permeability and causes leakage of Na/K, metabolic cell death

47
Q

Spectrum of amphotericin B

A

candida, cryptococcus neoformans, aspergillus, blastomyces dermatitidis, histoplasma capsulatum, mucor, coccidioides immitis

48
Q

Pk/Pd

A

IV only, zero penetration into the CNS

49
Q

ADRs of amphotericin B

A

lots of infusion related ADRs, HA, fever, chills, arthralgias, myalgias, N/V, hoTN, thrombophlebitis, also nephrotoxic, hypokalemia, hypomagnesemia (give K/Mg prophylaxis)

50
Q

Uses of amphotericin B

A

requires a test of tolerance, histoplasmosis, cryptococcosis, aspergillosis, disseminated candidiasis, empiric therapy in immunocompromised

51
Q

Liposomal amphotericin B pearls

A

better tolerated from ADR, able to treat CNS infxn, $$$

52
Q

Flucytosine (Ancobon) MOA

A

incorporated into fungal RNA to interfere w/ protein synthesis

53
Q

Spectrum of flucytosine (Ancobon)

A

cryptococcus neoformans, candida

54
Q

ADRs of flucytosine

A

Gi, bone marrow suppression

55
Q

Flucytosine uses

A

fes, usually combo w/ ampho B, crypto meningitis, invasive pulmonary cryptococcosis

56
Q

Terbinafine (Lamisil), MOA

A

Inhibits squalene epoxidase, key enzyme in fungal sterol synthesis, used as systemic therapy

57
Q

Clinical use terbinafine

A

onchomycosis (finger and toe), tinea capitis

58
Q

Nystatin MOA

A

Binds to sterol in fungal cell membrane drastically changing permeability

59
Q

Nystatin availability

A

PO suspension, powder, tablet, cream

60
Q

Nystatin use

A

cutaneous and mucocutaneous infxn

61
Q

Nystatin spectrum

A

candida

62
Q

candidemia tx in non-neutropenic pts

A

fluconazole is DOC, alternative- LFAmB, AmB, voriconazole, remove lines where appropriate, treat 14 days after first neg culture

63
Q

tx of candidemia in neutropenic pts

A

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
Q

TX of UTI caused by candida

A

asymptomatic cystitis- no tx, symptomatic cystitis- fluconazole- DOC amB if resistant, pyelonephritis- fluconazole

65
Q

TX of CNS candidiasis

A

LFAmB followed by fluconazole daily, tx continues until clinical improvement is evident

66
Q

Candida isolated from respiratory secretions

A

tx not recommended, candida rarely causes LRTI, mostly seen in immunocompromized, neutropenic pts

67
Q

Invasive pulmonary aspergillosis

A

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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