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Flashcards in Anti-Fungal Therapy Deck (36):
1

what has caused increased prevalence of systemic fungal infections?

overuse of antibiotics (esp. broad spectrum)
abx use has become a risk factor for getting systemic mycoses

2

what are superficial mycoses?

fungus that affects skin, hair and nails

3

what are subcutaneous mycoses?

fungus that affects the muscle, CT below the skin

4

what are systemic (invasive) mycoses?

involve internal organs,
primary and opportunistics

5

what are allergic mycoses?

fungus that affects the lungs or sinuses
pts may have chronic asthma, cystic fibrosis or sinusitis

6

what are fungal cell membranes made of?

ergosterol instead of cholesterol
-makes drug production specific to fungi that does not damage mammal cells

7

do fungi have cell walls?

yes

8

which are the polyene antibiotics that interfere with production of cell membrane?

amphotericin B
nystatin (typically topical)

9

which are the azole antifungals that interfere with production of cell membrane?

ketoconazole (nizoril)-imidazole-1st systemic antifungal that you could give orally
itraconazole (sporanox)-triazole
fluconazole (diflucan)-triazole
voriconazole (vfend)-2nd gen triazole
miconazole
clotrimazole

10

what is the MOA of azoles?

inhibit activity of lanosterol 14alpha demethylase which inhibits production of ergosterol
-some cross reactivity is found with CYP450
-some steroidogenesis problems in mammalian cells

11

when are ketoconazole used?

yeasts and molds
poor absorption and strong side effects
>99% protein binding
cleared through kidney and liver

12

what are side effects of ketoconazole?

N/V worse with higher doses
hepatotoxicity
dose related inhibition of CYP450 responsible for testosterone creation and cortisol formation

13

what will impact absorption of ketoconazole?

gastric pH

14

what is the go-to first systemic antifungal of choice

fluconazole

15

what are advantages of diflucan?

well tolerated
IV/PO formations are available
favorable pharmacokinetics
better bioavailability
hepatotoxicity is not present

16

what are disadvantages of fluconazole?

fungistatic not fungicidal
resistance is increasing
narrow spectrum
drug interactions

17

what is spectrum of fluconazole?

C. albicans
Cryptococcus neoformans

18

which fungi are not covered under fluconazole?

C. krusei
C. glabrata
aspergillus and other molds

19

what is the primary source of resistance against antifungals (esp. fluconazole)?

genetic mutations

efflux pumps (pump drug out of the cell)

20

what are side effects of fluconazole?

N/V rash more likely with high doses

21

what drug levels will fluconazole increase?

phenytoin
cyclosporin
rifabutin
warfarin
zidovudine

22

what drug levels decrease fluconazole?

rifampin

23

what are indicated uses of fluconazole?

mucosal candidiasis (vulvovaginal)
systemic fungal (IV)
maintenance of cryptococcal meningitis
-good CNS concentration

24

what are side effects of itraconazole?

taste disturbances
N/V
osmotic diarrhea esp at high doses (long term compliance is difficult)

25

what are side effects of voriconazole?

visual disturbances (returns to normal afterwards)
IV> oral

26

what are target organisms for amphotericin B?

aspergillus terreus, scedosporium spp
most lethal fungal cell killer

27

what are main uses of voriconazole?

other candida spp
aspergillus

28

what is the biggest side effect problem with amphotericin B?

nephrotoxic
top 5 most nephrotoxic drugs
(renovascular and tubulovascular)

29

how would you counteract the nephrotoxicity of amphotericin B?

volume load and load up with Na and K

30

what is amphotericin B used for?

cryptococcal meningitis (2nd line after fluconazole)
mucomycosis
invasive fungal infection that is not responding to other agents

31

what is the MOA of flucytosine?

interferes with fungal DNA generation

32

what is main drawback of flucytosine?

rapid resistance develops when used as a monotherapy
1. decreased uptake
2. altered 5FU metabolism

33

what are indicated uses of flucytosine?

in combo with ampotericin B or fluconazole to treat
-candidiasis
-cryptococcosis
-?aspergillosis

34

what are flucytosine side effects?

D/V, alterations in LFTs and anemia with long term use

35

what are MOAs of echinocandins, caspofungin and micafungin?

disrupt maintenance of cell wall

36

what are indications of echinocandins?

non albicans Candida or fluconazole resistant spp
Aspergillus

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