Antifungal agents Flashcards Preview

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Flashcards in Antifungal agents Deck (67):
1

Risk factors of fungal infections

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

2

Most commonly encountered fungi

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

3

Azoles options

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

4

Echinocandins options

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

5

Imidazole options

ketoconazole (Nizoral), clotrimazole, miconazole

6

Micallaneous options

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

7

Azole MOA

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

8

difulcan spectrum of activity

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

9

what are difulcan not affected against?

C. Krusei, aspergillus

10

PK of difulcan

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

11

Clinical use of difulcan

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

12

ADR of Difulcan

very well tolerated, elevation of LFT, N/V

13

DI of difulcan

worry more about these, HCTZ, warfarin, phenytoin

14

Dosing of difulcan

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

15

itraconazole MOA

inhibits ergosterol synthesis, fungistatic

16

Spectrum of activity of itraconazole

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

17

clinical use of itraconazole

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

18

Voriconazole MOA

inhibits ergosterol synthesis, fungistatic

19

Voriconazole spectrum

aspergillus, including amphotericin resistant, all candida, cryptococcus neoformans

20

Voriconazole kinetics

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

21

DI of voriconazole

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

22

Voriconazole clinical uses

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

23

Posaconazole (noxafil) MOA

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

24

Spectrum of activity of posaconazole

aspergillus, candida, cryptococcus neoformans, very broad

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