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CMD Block 2 > Antifungal Drug Targets > Flashcards

Antifungal Drug Targets Flashcards

1
Q

Which of the following routes 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

Amphotericin works by

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 to:

A

diminish renal damage

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4
Q

Antifungal that most closely related to the anticancer drug 5-fluorouracil (5-fu).

A

flucytosine

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5
Q

Which 2 antifungals would most likely produce bone marrow suppression as an adverse effect?

A 
flucytosine
ampho B (decreased EPO, thus associated with anemia)
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6
Q

Blurring and changes in color vision or brightness are most commonly associated with the use of:

A

voriconazole

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7
Q

Which organs are likely to be affected by flucytosine?

A

hepatic

GI

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8
Q

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

A

lower selectivity for fungal CYPs

more toxic to humans

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9
Q

Which antifungal possesses the broadest spectrum of anti fungal activity?

A

amphotericin B

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10
Q

Amphotericin liposomal formulations provide for:

A

diminished renal toxicity

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11
Q

Which antifungal would most likely give rise to gynecomastia and impotence in males

A

ketoconazole

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12
Q

Which of the following inhibits the production of ergosterol through a non-CYP mediated event? flucytosine, caspfungin, nystatin, posaconazole, terbinafine

A

terbinafine

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13
Q

Class of drug that affects CYP450

A

Azoles

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14
Q

This drug can be given intrathecally to fight meningitis (but is not really the first choice).

A

Ampho B

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15
Q

When given prophylactically, reduces fungal disease in BM transplant and AIDS patients

A

fluconazole

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16
Q

Drug shows reduced F when taken with rifamycins:

A

itraconazole

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17
Q

Interferes with microtubule function:

A

Griseofulvin

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18
Q

Deposited in newly forming skin where it binds to keratin, protecting skin from new infection

A

Griseofulvin

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19
Q

Drug interactions with warfarin and phenobarbital:

A

Griseofulvin

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20
Q

Commonly used for suppression of local candidal infections

A

Nystatin

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21
Q

Cause abnormalities in liver enzymes

A

AZOLES

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22
Q

Flucytosine has a ______ therapeutic window and a _____ spectrum

A

narrow; narrow

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23
Q

Widest therapeutic index of azoles

A

fluconazole

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24
Q

Treats dimorphic fungi (Histoplasma), Aspergillus, Coccidioides cryptococcus

A

itraconazole

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25
Tx of choice for Aspergillus; Works well against Candida and dimorphic fungi
voriconazole
26
Inhibitor of CYP3A4, so dosage modification of many meds are required.
voriconazole
27
Broadest spectrum of azole family
Posaconazole
28
Fungicidal by inhibiting synthesis of Beta(1-3)-glucan
Echinocandins
29
Inhibits fungal enzyme squalene epoxidase (accumulation of sterol squalene is toxic)
Terbinafine
30
How is amphotericin B administered?
IV; orally ONLY if you want to treat the GI lumen
31
Why is liposomal ampho B more favorable?
preferential binding reduces toxicity, increases efficacy | drug can be released by fungal lipases
32
2 mechanisms of ampho B resistance:
1. altered sterol target | 2. decreased ergosterol in membrane
33
How do you decrease the infusion-related toxicity of ampho B?
slow infusion rate | decrease daily dose
34
What toxicities are associated with Ampho B?
anemia (due to increased EPO) renal hepatic (plus infusion-related-- HA, fever, chills, NV, etc)
35
Taken up in fungal cells by cytosine permease
flucytosine
36
Inhibits fungal DNA/RNA synthesis
flucytosine (converted to FdUMP and FUTP)
37
Why is flucytosine not used alone?
synergy with other drugs | resistance prevention
38
Azoles inhibit fungi by:
reducing ergosterol synthesis via fungal CYP450 inhibition
39
Most common azole side effect:
mild GI upset
40
Prone to drug interactions in humans:
azoles (CYP450 inhibitors)
41
Reduced bioavailability when taken with rifamycins
itraconazole
42
Treats dimorphic fungi, dermatophytoses, onychomycosis
itraconazole | and perhaps voriconazole?
43
Often given prophylactically to AIDS and BM transplant patients
fluconazole
44
Good CSF penetration, good cryptococcal meningitis therapy
fluconazole
45
May increase substrate levels of any cyclosporines, tacrolimus, and statins that are taken in conjunction due to CYP3A4 inhibition
voriconazole
46
Best treatment for invasive aspergillosis
voriconazole
47
Indicated for mucormycosis and prophylaxis of infections in chemo, BM transplant and graft-vs-host disease
posaconazole
48
Disrupts cell wall by inhibiting beta(1-3)glycan synthesis
echinocandins
49
Mostly used to treat candidal infections (only)
echinocandins
50
Caspofungin (an echinocandin) and cyclosporine, when given together, cause:
elevated liver enzymes
51
Anidulafungin may cause the release of _____ during IV infusion.
histamine
52
Only used in systemic trx of dermatophytosis
griseofulvin
53
Binds to keratin, protecting skin from new infection (fungistatic)
griseofulvin
54
May cause allergic syndrome, hepatitis, drug interactions with warfarin/phenobarbital
griseofulvin
55
Fungicidal keratin-binding drug
terbinafine
56
Inhibits squalene epoxidase, which causes squalene accumulation and toxicity
terbinafine | this somehow affects ergosterol synthesis?
57
Suppresses local candidal infections via topical prep
nystatin
58
Topical clotrimazole and miconazole treat:
vulvovaginal candidiasis
59
Inhibits fungal mitosis
griseofulvin
60
Fungal drug class that causes QT prolongation
azoles
61
Antifungal drug that causes cardiomyopathy
itraconazole
62
Antifungal that is a substrate for and inhibitor of CYP2C19
voriconazole
63
Antifungal class that inhibits ergosterol synthesis by blocking 14-alpha demethylase
azoles | needed to convert lanosterol to ergosterol
64
What causes serum concentration variability when taking voriconazole?
gene polymorphisms
65
Ketoconazole inhibits what mammalian process, thus causing unpleasant side effects
steroid synthesis

CMD Block 2 (38 decks)

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