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Host and Defense > EXAM 3 Antifungal Drugs > Flashcards

EXAM 3 Antifungal Drugs Flashcards

1
Q

fungi are mostly eukaryotic organisms that live as ___ or ___

A

saprobes or parasites

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2
Q

fungi have a ___ cell wall composed of ___

A
  • rigid
  • chitin
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3
Q

the fungal cell membrane is composed of ___, which acts like cholesterol in the human cell membranes

A

ergosterol

unlike eukaryotes, bacterial membranes generally do not contain sterols

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4
Q

are antibacterial agents effective against fungal infections?

A

no

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5
Q

___ fungal infections involve the skin and other soft tissues

A

superficial

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6
Q

___ fungal infections involve the whole body and are thus a major cause of death in immunocompromised patients

A

systemic

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7
Q

antifungal agents target what 4 things?

A
  • fungal cell membrane
  • cell wall synthesis
  • nucleic acid synthesis (DNA and RNA)
  • microtubule function
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8
Q

what 3 drugs are the primary drugs used for treating systemic fungal infections?

A

amphotericin B, azoles, and echinocandins

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9
Q

how are amphotericin B, azoles, and echinocandins selectively toxic to fungi?

A

they interact with or inhibit ergosterol synthesis, a sterol unique to fungal cell membranes

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10
Q

which drugs work by disrupting fungal cell membrane function and permeability?

A

amphotericin B, nystatin, itraconazole, fluconazole, naftifine, and terbinafine

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11
Q

which drugs are the polyenes that bind to ergosterol in fungal cell membranes to disrupt membrane function and permeability?

A

amphotericin B and nystatin

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12
Q

which two imidazoles and triazoles inhibit 14-alpha-sterol demethylase, prevent ergosterol synthesis, and lead to accumulation of 14-alpha-methylsterols?

A

itraconazole and fluconazole

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13
Q

which allylamines inhibit squalene epoxidase and prevent ergosterol synthesis?

A

naftifine and terbinafine

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14
Q

which drug inhibits fungal cell wall synthesis?

A

caspofungin

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15
Q

describe polyene antibiotics

A
  • amphotericin B and nystatin
  • fungistatic
  • bind to plasma membrane ergosterol and damages the membrane by forming pores which cause leakage of potassium ions
    *
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16
Q

what is the spectrum of amphotericin B?

A

broad spectrum: effective against most serious systemic fungal infections

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17
Q

how is amphotericin B administered?

A

parenteral only; usually given IV in hospital setting

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18
Q

what are the common side effects of amphotericin B?

A
  • highly toxic chronic reactions (nephrotoxic and neurotoxic) at higher doses
  • immediate reactions - infusion related toxicity
  • slower reactions - renal toxicity and neurotoxicity
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19
Q

___ is the first line therapy for invasive, life-threatening systemic and localized candidemia, and is also effective for aspergillus infections

A

amphotericin B

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20
Q

___ is often reserved for severe infections in critically ill or immunocompromised patients due to its extensive side effects

A

amphotericin B

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21
Q

how is nystatin administered?

A

topical only

not absorbed well but still too toxic if ingested orally

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22
Q

what are the clinical uses of nystatin?

A
  • availabe as a mouthwash or cream
  • topical treatment for oral and esophageal candidiasis albicans (thrush) as mouthwash
  • topical cream for vaginal candidiasis (yeast infections)
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23
Q

what are the adverse effects of nystatin?

A
  • higher systemic toxicity, so should never be administered systemically
  • disulfuram-like reactions
24
Q

describe the classifications of azole antifungals

A
  • based on the number of nitrogen atoms attached to the ring
  • imidazoles - 2 nitrogen atoms
  • triazoles - 3 nitrogen atoms
25
Q

what is the mechanism of azole antifungals?

A

inhibit ergosterol synthesis by blocking lanosine 14-alpha-demethylase

26
Q

how are azole antifungals administered?

A

topically or systemically depending on drug and use

27
Q

what are the contraindications of azole antifungals?

A

pregnancy, during lactation, or in patients with hepatic dysfunction

28
Q

what drugs lack selectivity and inhibit human gonadal and steroid synthesis, cause loss of libido/impotency, gynecomastia in males, menstrual irregularity in females, and hypercortilism, and are hepatotoxic?

A

azole antifungals

29
Q

which azole antifungal drug is the most commonly prescribed systemic antifungal, is the drug of choice for most candidiasis albicans, does not treat aspergillis, and is used to treat fungal cryptococcal meningitis in AIDs patients?

A

fluconazole

30
Q

which azole antifungal drug is highly teratogenic and should be avoided during pregnancy?

A

fluconazole

31
Q

which azole antifungal drug was the first azole used for systemic and topical therapy?

A

ketoconazole

32
Q

which azole antifungal drug is more toxic than fluconazole, but is effective against aspergillis?

A

itraconazole

33
Q

which two azole antifungals are available over the counter, topical only, and are used to treat vulvo-vaginal candidiasis (yeast infection), oral candidiasis (as lozenge), or as ointment for athlete’s foot and jock rash (dermatophytosis)?

A

clotrimazole and miconazole

34
Q

which azole antifungal is the 1st line treatment for aspergillis infections?

A

vorconizole

35
Q

ketoconazole should never be given with ___

A

amphotericin B

36
Q

what is the mechanism of flucytosine?

A

inhibits thymidylate synthetase which inhibits both DNA and RNA synthesis in fungi

37
Q

describe the spectrum of flucytosine

A

narrow spectrum, for systemic fungal infections

38
Q

how is flucytosine administered?

A
  • well absorbed after oral administration
  • concentration in CSF is 50-90% that in plasma, making it good for fungal meningitis
39
Q

___ is synergistic when given in combination with amphotericin B for cryptococcol meningitis

A

flucytosine

40
Q

___ is the main adverse effect of flucytosine

A

bone marrow suppression

41
Q

what is the mechanism of echinocandins (caspofungin)?

A

block cell wall synthesis and maintenance via inhibition of 1,3-beta glucan synthase

42
Q

which class of drugs are fungicidal against some candida species, fungistatic against some molds (aspergillis), and are used in azole-resistant candida or as a 2nd line agent for refractory aspergillosis?

A

echinocandins (ex. caspofungin)

43
Q

echinocandins (caspofungin) is adminstered ___

A

IV

44
Q

___ is embryotoxic (category C) and thus should be avoided if possible in pregnancy

A

echinocandins (ex. caspofungin)

45
Q

___ binds to and disrupts microtubule function, inhibiting fungal mitosis

A

griseofulvin

46
Q

griseofulvin inhibits the growth of ___

A

dermatophytes

47
Q

is griseofulvin used commonly?

A

rarely used anymore - largely replaced by terbinafine

48
Q

griseofulvin is not effective topically, and has entirely ___ effects

A

local

49
Q

___ induces human CYP that metabolized drugs like warfarin (increase metabolism)

A

griseofulvin

50
Q

what are the adverse effects of griseofulvin?

A

teratogenic, carcinogenic, and severe headaches

51
Q

what is the mechanism of terbinafine?

A

inhibits the fungal enzyme squalene epoxidase to inhibit ergosterol synthesis, which disrupts cell membrane permeability

52
Q

___ is used for treating dermatophytes, and has largely replaced griseofulvin for treatment of onychomycosis

A

terbinafine

53
Q

what is the adverse effect of terbinafine?

A

hepatotoxic

54
Q

___ antifungals are used for localized candidiasis in pateints with normal immune function

A

topical

55
Q

___ antifungals are used for disseminated disease and in immunocompromised patients

A

systemic

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