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Antifungals Flashcards

1
Q

Which route of antifungal administration is most suited to the treatment of a minor fungal infection of the toenail?

A

topical

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2
Q

what is the mechanism for Amphotericin?

A

binding ergosterol and forming pores in the cell wall

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3
Q

Normal saline is infused in a patient receiving amphotericin B why?

A

diminish renal damage

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4
Q

which antifungal can produce bone marrow supression?

A

flucytosine

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5
Q

Blurring and changes in color vision or brightness (i.e., photosensitivity and photopsia) is associated with which antifungal?

A

voriconazole

think: voricon ~ VISION

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6
Q

Which organ system(s) is are likely to be affected by flucytosine?

A

GI

hepatic

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7
Q

The imidazole drug, ketoconazole, is distinguished from the triazoles, like fluconazole, by its:

A

lower selectivity for fungal CYPs

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8
Q

Which antifungal possess the broadest spectrum of anti fungal activity?
*with grain of salt

A

amphotericin B

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9
Q

Amphotericin liposomal formulations provide for what? why?

A

diminished renal toxicity

decreased binding of the drug to renal cells

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10
Q

Clinical use of which of the following antifungals would most likely give rise to gynecomastia and impotence in males?

A

ketoconazole

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11
Q

Which of the following inhibits the production of ergosterol through a non-CYP mediated event?

A

terbinafine

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12
Q

which antifungals are polyenes?

A

amphotericin B

nystatin (not used systemically - toxic)

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13
Q

whatever happened to amphotericin A?

A

not in clinical use

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14
Q

which antifungal is a flucytosine?

A

5-fluorocytosine

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15
Q

which antifungals are in the -azole//conazole family?

A

ketoconazole
fluconazole
itraconazole
voriconazole

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16
Q

name drugs that you would administer for a ifungal systemic infection

A

amphotericin B (polyene)
flucytosine
azoles

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17
Q

name systemic drugs that you would administer for a superficial fungal infection

A

griseofulvin
terbafine
azole (except voriconazole)

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18
Q

what are some topical antifungals?

A

nystatin (polyene)
miconazole
clotrimazole

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19
Q

what organ system is amphotericin B not delivered to?

A

CNS

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20
Q

which drug could build up in a pt relying on dialysis or with extreme real dysfunction? why?

A

amphotericin B

  • not dialyzable :: would become toxic
  • slow hepatic metabolism
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21
Q

are polyenes hydrophillic or phobic? why is this important?

A

they are ampiphatic

important because it allows them to bind to ergosterol and insert into fungal memb to form pore

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22
Q

what is the mechanism of amphotericin B (or other polyenes)?

A

binds to ergotserol
inserts in membrane
creates a pore

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23
Q

what is the reason for dose-limiting amphotericin B?

A

nephrotoxic effects:

  • decreases GFR
  • causes renal tubular acidosis
  • magnesium, potassium wasting
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24
Q

what antifungal drug may cause anemia? why?

A

amphotericin B

decreases in renal formation of erythropoietin

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25
Q

what is the mechanism for flucytosine?

A

blocks nucleic acid (thus, DNA) synthesis

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26
Q

what are the two enzymes involved in flucytosine mechanism? why is this important?

A
  1. permease: gets drug across membrane
  2. cytosine deaminase: converts to 5-FU

important bc “selective toxicity” occurs; mammalian cells have low levels of these

27
Q

what enzyme is blocked in the mechanism of flucytosine?

A

production of 5-FU inhibits

thymidylate synthase

28
Q

what are the toxic effects from prolonged high plasma levels of flucytosine?

A
  • bone marrow depression
  • alopecia
  • liver dysfunction
29
Q

what is required for oral absorption of an azole drug?

A

normal gastric acidity

30
Q

which azole is not distributed to the CNS?

A

fluconazole

31
Q

which azole is eliminated by the kidneys? in what form?

A

fluconazole

mostly unchanged form

32
Q

what is the mechanism for the azoles?

A

inhibit the synthesis of ergosterol :: altering fungal cell membrane permeability

33
Q

what catalyzes the reaction that azoles interrupt? what kind of reaction is it?

A

4-alpha demethylation, a fungal CYP450

a demethylation to lanosterol

34
Q

what anti-fungal is a notorious inhibitor of CYP450? this results in _____ levels of some other drugs.

A

ketoconazole

increased

35
Q

what antifungal results in adrenal and gonadal steroids? how?

A

ketoconazole

inhibits CYP450 :: production of androsterone from cortisol

36
Q

what conditions (from toxicity) can ketoconazole cause?

A

gynecomastia
menstrual irregularities
infertility

37
Q

do the non-ketoconazole azos inhbit CYP450?

A

yes, just are more selective

38
Q

what antifungal carries some potential pregnacy risk? what class is it?

A

voriconazole

class D (animal studies)

39
Q

mechanism of action for caspofungin/echinocandins

A

inhibit synthesis of beta(1-3)D-glycan :: inhibit cell wall

40
Q

mechanism of action for griseofulvin

A

interference of microtubule function :: inhibit mitosis

possibly inhibit nucleic acid synthesis

41
Q

how can resistance be built up to griseofulvin?

A

decrease in the energy-dependent transport that the drug uses to get in fungal cell

42
Q

how can resistance develop to flucytosine?

A

decreased activity of the target enzymes (permease and deaminase)

43
Q

how can resistance develop in azoles?

A

changes in sensitivity of the target enzymes (14-alpha-demethylase)

44
Q

how can resistance develop in amphotericin B?

A

decreased level of structural change

uncommon

45
Q

what anti-fungal absorption is aided by high-fat foods?

A

griseofulvin

46
Q

what antifungal drug relies on biliary excretion?

A

griseofulvin

47
Q

what drug does griseofulvin decrease availability of? what is the consequence?

A

warfarin

decreased anti-coagulant effect

48
Q

3 negative issues with voriconazole?

A
  1. mental confusion/CNS problems
  2. pregnancy risk (class D)
  3. photopsia (flashes of light)
49
Q

what is the mechanism for terbafine/allylamines?

A

interrupts cell wall component ergosterol

inhibits fungal enzyme squalene monooxygenase, which causes toxic levels of squalene, which interferes with ergosterol synthesis

50
Q

three major mechanisms to antifungals

A
  1. cell wall
  2. cell membrane (ergosterol)
  3. intracellular (genome replication)
51
Q

which two antifungals can cause infusion reactions?

A

amphotericin B

echinocandins

52
Q

what is a common side effect of all antifungals?

A

rash

53
Q

which antifungal carries a risk of photosensitivity? what does this then put the pt at risk for?

A

voriconazole

malignancy (melanoma)

54
Q

what antifungal toxicity is associated with cardiomyopathy?

A

itraconazole

55
Q

what antifungal class is associated with QT prolongation? especially under what circumstances?

A

azoles

especially with drug interactions

56
Q

three antifungals that can cause GI toxicity

A

itraconazole
posaconazole
5-FC

57
Q

which antifungal has variable toxicity? what is this due to?**

A

vericonazole

variable toxicity due to genetic polymorphism of CYP enzyme

58
Q

what CYP enzyme does vericonazole inhibit?

A

CYP2C19

59
Q

do the (lack of) androgen side effects abate when ketoconazole is discontinued, or are the permanent?

A

discontinue

60
Q

which antifungal is hepatotoxic at high doses?

A

ketoconazole

61
Q

which azoles can cause QT prolongation?

A

fluconazole
posaconazole
voriconazole

62
Q

which fungal drug has renal excretion?**

A

fluconazole

63
Q

which antifungal drug can have high concentrations in the CSF?**

A

fluconazole

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