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Pharmacology (Sweatman) > Antifungals > Flashcards

Antifungals Flashcards

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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
what is the mechanism for flucytosine?
blocks nucleic acid (thus, DNA) synthesis
26
what are the two enzymes involved in flucytosine mechanism? why is this important?
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
what enzyme is blocked in the mechanism of flucytosine?
production of 5-FU inhibits thymidylate synthase
28
what are the toxic effects from prolonged high plasma levels of flucytosine?
- bone marrow depression - alopecia - liver dysfunction
29
what is required for oral absorption of an azole drug?
normal gastric acidity
30
which azole is not distributed to the CNS?
fluconazole
31
which azole is eliminated by the kidneys? in what form?
fluconazole mostly unchanged form
32
what is the mechanism for the azoles?
inhibit the synthesis of ergosterol :: altering fungal cell membrane permeability
33
what catalyzes the reaction that azoles interrupt? what kind of reaction is it?
4-alpha demethylation, a fungal CYP450 a demethylation to lanosterol
34
what anti-fungal is a notorious inhibitor of CYP450? this results in _____ levels of some other drugs.
ketoconazole increased
35
what antifungal results in adrenal and gonadal steroids? how?
ketoconazole inhibits CYP450 :: production of androsterone from cortisol
36
what conditions (from toxicity) can ketoconazole cause?
gynecomastia menstrual irregularities infertility
37
do the non-ketoconazole azos inhbit CYP450?
yes, just are more selective
38
what antifungal carries some potential pregnacy risk? what class is it?
voriconazole class D (animal studies)
39
mechanism of action for caspofungin/echinocandins
inhibit synthesis of beta(1-3)D-glycan :: inhibit cell wall
40
mechanism of action for griseofulvin
interference of microtubule function :: inhibit mitosis possibly inhibit nucleic acid synthesis
41
how can resistance be built up to griseofulvin?
decrease in the energy-dependent transport that the drug uses to get in fungal cell
42
how can resistance develop to flucytosine?
decreased activity of the target enzymes (permease and deaminase)
43
how can resistance develop in azoles?
changes in sensitivity of the target enzymes (14-alpha-demethylase)
44
how can resistance develop in amphotericin B?
decreased level of structural change uncommon
45
what anti-fungal absorption is aided by high-fat foods?
griseofulvin
46
what antifungal drug relies on biliary excretion?
griseofulvin
47
what drug does griseofulvin decrease availability of? what is the consequence?
warfarin decreased anti-coagulant effect
48
3 negative issues with voriconazole?
1. mental confusion/CNS problems 2. pregnancy risk (class D) 3. photopsia (flashes of light)
49
what is the mechanism for terbafine/allylamines?
interrupts cell wall component ergosterol inhibits fungal enzyme squalene monooxygenase, which causes toxic levels of squalene, which interferes with ergosterol synthesis
50
three major mechanisms to antifungals
1. cell wall 2. cell membrane (ergosterol) 3. intracellular (genome replication)
51
which two antifungals can cause infusion reactions?
amphotericin B | echinocandins
52
what is a common side effect of all antifungals?
rash
53
which antifungal carries a risk of photosensitivity? what does this then put the pt at risk for?
voriconazole malignancy (melanoma)
54
what antifungal toxicity is associated with cardiomyopathy?
itraconazole
55
what antifungal class is associated with QT prolongation? especially under what circumstances?
azoles especially with drug interactions
56
three antifungals that can cause GI toxicity
itraconazole posaconazole 5-FC
57
which antifungal has variable toxicity? what is this due to?**
vericonazole variable toxicity due to genetic polymorphism of CYP enzyme
58
what CYP enzyme does vericonazole inhibit?
CYP2C19
59
do the (lack of) androgen side effects abate when ketoconazole is discontinued, or are the permanent?
discontinue
60
which antifungal is hepatotoxic at high doses?
ketoconazole
61
which azoles can cause QT prolongation?
fluconazole posaconazole voriconazole
62
which fungal drug has renal excretion?**
fluconazole
63
which antifungal drug can have high concentrations in the CSF?**
fluconazole

Pharmacology (Sweatman) (3 decks)

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