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Medicine > Anti-Fungal Therapy > Flashcards

Anti-Fungal Therapy Flashcards

1
Q

what has caused increased prevalence of systemic fungal infections?

A

overuse of antibiotics (esp. broad spectrum)

abx use has become a risk factor for getting systemic mycoses

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2
Q

what are superficial mycoses?

A

fungus that affects skin, hair and nails

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3
Q

what are subcutaneous mycoses?

A

fungus that affects the muscle, CT below the skin

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4
Q

what are systemic (invasive) mycoses?

A

involve internal organs,

primary and opportunistics

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5
Q

what are allergic mycoses?

A

fungus that affects the lungs or sinuses

pts may have chronic asthma, cystic fibrosis or sinusitis

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6
Q

what are fungal cell membranes made of?

A

ergosterol instead of cholesterol

-makes drug production specific to fungi that does not damage mammal cells

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7
Q

do fungi have cell walls?

A

yes

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8
Q

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

A

amphotericin B

nystatin (typically topical)

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9
Q

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

A 
ketoconazole (nizoril)-imidazole-1st systemic antifungal that you could give orally
itraconazole (sporanox)-triazole
fluconazole (diflucan)-triazole
voriconazole (vfend)-2nd gen triazole
miconazole
clotrimazole
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10
Q

what is the MOA of azoles?

A

inhibit activity of lanosterol 14alpha demethylase which inhibits production of ergosterol

  • some cross reactivity is found with CYP450
  • some steroidogenesis problems in mammalian cells
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11
Q

when are ketoconazole used?

A

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

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12
Q

what are side effects of ketoconazole?

A

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

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13
Q

what will impact absorption of ketoconazole?

A

gastric pH

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14
Q

what is the go-to first systemic antifungal of choice

A

fluconazole

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15
Q

what are advantages of diflucan?

A 
well tolerated
IV/PO formations are available
favorable pharmacokinetics
better bioavailability
hepatotoxicity is not present
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16
Q

what are disadvantages of fluconazole?

A

fungistatic not fungicidal
resistance is increasing
narrow spectrum
drug interactions

17
Q

what is spectrum of fluconazole?

A

C. albicans

Cryptococcus neoformans

18
Q

which fungi are not covered under fluconazole?

A

C. krusei
C. glabrata
aspergillus and other molds

19
Q

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

A

genetic mutations

efflux pumps (pump drug out of the cell)

20
Q

what are side effects of fluconazole?

A

N/V rash more likely with high doses

21
Q

what drug levels will fluconazole increase?

A 
phenytoin
cyclosporin
rifabutin
warfarin
zidovudine
22
Q

what drug levels decrease fluconazole?

A

rifampin

23
Q

what are indicated uses of fluconazole?

A 
mucosal candidiasis (vulvovaginal)
systemic fungal (IV)
maintenance of cryptococcal meningitis
-good CNS concentration
24
Q

what are side effects of itraconazole?

A

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

25
Q

what are side effects of voriconazole?

A 
visual disturbances (returns to normal afterwards)
IV> oral
26
Q

what are target organisms for amphotericin B?

A

aspergillus terreus, scedosporium spp

most lethal fungal cell killer

27
Q

what are main uses of voriconazole?

A

other candida spp

aspergillus

28
Q

what is the biggest side effect problem with amphotericin B?

A

nephrotoxic
top 5 most nephrotoxic drugs
(renovascular and tubulovascular)

29
Q

how would you counteract the nephrotoxicity of amphotericin B?

A

volume load and load up with Na and K

30
Q

what is amphotericin B used for?

A

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

31
Q

what is the MOA of flucytosine?

A

interferes with fungal DNA generation

32
Q

what is main drawback of flucytosine?

A

rapid resistance develops when used as a monotherapy

  1. decreased uptake
  2. altered 5FU metabolism
33
Q

what are indicated uses of flucytosine?

A

in combo with ampotericin B or fluconazole to treat

  • candidiasis
  • cryptococcosis
  • ?aspergillosis
34
Q

what are flucytosine side effects?

A

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

35
Q

what are MOAs of echinocandins, caspofungin and micafungin?

A

disrupt maintenance of cell wall

36
Q

what are indications of echinocandins?

A

non albicans Candida or fluconazole resistant spp

Aspergillus

Medicine (146 decks)

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