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therapeutics V > Antifungal Agents > Flashcards

Antifungal Agents Flashcards

1
Q

What is the mechanism of action of amphotericin B?

A

Binds to ergosterol in fungal membranes, forming pores that cause cell leakage.

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2
Q

What is the mechanism of action of azoles?

A

Inhibit lanosterol 14-α-demethylase, preventing ergosterol synthesis.

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3
Q

What is the mechanism of action of echinocandins?

A

Inhibit β-1,3-glucan synthase, disrupting fungal cell wall.

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4
Q

What is the mechanism of action of flucytosine?

A

Converted to 5-FU, interferes with fungal RNA and DNA synthesis.

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5
Q

What is the mechanism of action of terbinafine?

A

Inhibits squalene epoxidase, leading to accumulation of toxic squalene.

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6
Q

Which antifungals cover Aspergillus?

A

Voriconazole, Posaconazole, Isavuconazole, Amphotericin B, and echinocandins (partial).

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7
Q

Which antifungals cover Candida auris?

A

Echinocandins, Amphotericin B, Voriconazole, and Isavuconazole (partial).

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8
Q

Which antifungals have activity against Mucorales?

A

Amphotericin B, Posaconazole, and Isavuconazole.

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9
Q

Which azoles are first-line for invasive fungal infections?

A

Voriconazole, Isavuconazole, and Posaconazole depending on the infection.

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10
Q

What are common adverse effects of amphotericin B?

A

Nephrotoxicity, infusion reactions, electrolyte imbalances.

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11
Q

What are common side effects of azoles?

A

Hepatotoxicity, QTc prolongation, GI upset, drug interactions.

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12
Q

Which azole is associated with visual disturbances and phototoxicity?

A

Voriconazole.

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13
Q

What are common side effects of echinocandins?

A

Infusion reactions, elevated LFTs, histamine-mediated effects.

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14
Q

Which antifungals require therapeutic drug monitoring (TDM)?

A

Flucytosine, Voriconazole, Posaconazole, Itraconazole.

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15
Q

Why is flucytosine monitored with TDM?

A

To avoid bone marrow suppression and toxicity at high levels.

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16
Q

What is the target trough level for voriconazole?

A

1–1.5 μg/mL for efficacy; >5–6 μg/mL increases CNS toxicity.

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17
Q

Which antifungal has the longest half-life?

A

Isavuconazole (~130 hours).

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18
Q

Which antifungal is best tolerated in renal dysfunction?

A

Isavuconazole (no cyclodextrin).

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19
Q

What is the standard oral dose for fluconazole for OPC?

A

200 mg on day 1, then 100–200 mg daily for 7–14 days.

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20
Q

What is the first-line treatment for OPC?

A

Fluconazole 100–200 mg daily.

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21
Q

What is used for fluconazole-refractory OPC?

A

Itraconazole, Posaconazole, Voriconazole, echinocandins.

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22
Q

What is the duration of therapy for esophageal candidiasis?

A

14–21 days.

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23
Q

What is first-line treatment for uncomplicated VVC?

A

Single dose oral fluconazole 150 mg or topical azoles.

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24
Q

What is the treatment for complicated VVC in pregnancy?

A

Topical azoles for 7 days.

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25
How is recurrent VVC treated?
Induction with azole for 10–14 days, then fluconazole 150 mg weekly for 6 months.
26
Which azoles require an acidic environment for absorption?
Itraconazole and Posaconazole oral suspension.
27
Which azoles are available as IV formulations using cyclodextrin?
Voriconazole, Posaconazole, and Itraconazole.
28
Which azoles do NOT require renal adjustment?
Isavuconazole and Fluconazole.
29
Why do azoles have significant drug interactions?
They inhibit cytochrome P450 enzymes, especially CYP3A4.
30
Which azole has the highest potential for drug interactions?
Ketoconazole.
31
Which azole has the least CYP450 inhibition?
Isavuconazole.
32
What is a major adverse effect of itraconazole?
Congestive heart failure (negative inotrope).
33
What are major toxicities of voriconazole?
Visual disturbances, phototoxicity, hepatotoxicity.
34
What are major toxicities of amphotericin B?
Nephrotoxicity, hypokalemia, infusion-related reactions.
35
Which antifungal has the broadest coverage?
Amphotericin B.
36
Which azole is first-line for invasive aspergillosis?
Voriconazole.
37
Which antifungals have reliable activity against C. krusei?
Voriconazole, Posaconazole, Isavuconazole, Amphotericin B.
38
Which antifungals cover C. glabrata?
Echinocandins > Amphotericin B > high-dose Fluconazole.
39
What is the preferred antifungal for candidemia in the ICU?
An echinocandin.
40
When is fluconazole used first-line?
Uncomplicated mucocutaneous candidiasis (OPC, VVC).
41
What is the role of isavuconazole?
Treatment of invasive aspergillosis and mucormycosis.
42
Why is ketoconazole rarely used systemically?
Due to hepatotoxicity and drug interaction profile.
43
What antifungal has a loading dose followed by weekly maintenance?
Rezafungin.
44
Which antifungal is a triterpenoid with oral bioavailability?
Ibrexafungerp.
45
Which antifungal acts on fungal protein synthesis by inhibiting tRNA synthetase?
Tavaborole.
46
What class is Amphotericin B?
Polyene.
47
What is the mechanism of Amphotericin B?
Binds ergosterol and forms membrane pores.
48
What is the spectrum of Amphotericin B?
Broad: Candida, Aspergillus, Cryptococcus, Mucorales.
49
What are toxicities of Amphotericin B?
Nephrotoxicity, infusion reactions, electrolyte disturbances.
50
What is a benefit of liposomal Amphotericin B?
Less nephrotoxic than conventional formulation.
51
What class is Fluconazole?
Triazole.
52
What is the mechanism of Fluconazole?
Inhibits 14-α-demethylase to block ergosterol synthesis.
53
What is the spectrum of Fluconazole?
Candida albicans, C. parapsilosis, Cryptococcus.
54
What are toxicities of Fluconazole?
Hepatotoxicity, QTc prolongation.
55
What is a key feature of Fluconazole?
Renally eliminated, high oral bioavailability.
56
What class is Voriconazole?
Triazole.
57
What is the mechanism of Voriconazole?
Inhibits 14-α-demethylase.
58
What is the spectrum of Voriconazole?
Candida spp., Aspergillus, Fusarium.
59
What are toxicities of Voriconazole?
Visual disturbances, hepatotoxicity, phototoxicity.
60
What monitoring is needed with Voriconazole?
Therapeutic drug monitoring due to narrow therapeutic range.
61
What class is Posaconazole?
Triazole.
62
What is the spectrum of Posaconazole?
Candida, Aspergillus, Mucorales.
63
What is a key feature of Posaconazole?
Requires high-fat meal or delayed-release tablet for absorption.
64
What are toxicities of Posaconazole?
GI upset, hepatotoxicity, QTc prolongation.
65
When is Posaconazole used?
Prophylaxis in immunocompromised patients.
66
What class is Isavuconazole?
Triazole.
67
What is the spectrum of Isavuconazole?
Aspergillus, Mucorales.
68
What is a key benefit of Isavuconazole?
Shortens QTc and does not require cyclodextrin.
69
What are toxicities of Isavuconazole?
GI upset, hepatotoxicity, headache.
70
What is a key PK property of Isavuconazole?
Very long half-life (~130 hours).
71
What is the class of Caspofungin, Micafungin, and Anidulafungin?
Echinocandins.
72
What is the mechanism of Echinocandins?
Inhibit β-1,3-glucan synthase, weakening fungal cell wall.
73
What is the spectrum of Echinocandins?
Candida spp., some Aspergillus activity.
74
What are toxicities of Echinocandins?
Infusion-related reactions, LFT elevation.
75
What is a limitation of Echinocandins?
No coverage for Cryptococcus or Mucorales.
76
What class is Flucytosine?
Pyrimidine analog.
77
What is the mechanism of Flucytosine?
Converted to 5-FU → inhibits DNA/RNA synthesis.
78
What is the spectrum of Flucytosine?
Cryptococcus, Candida (synergy).
79
What are toxicities of Flucytosine?
Bone marrow suppression, GI upset.
80
When is Flucytosine used?
In combination with amphotericin B for cryptococcal meningitis.
81
What class is Terbinafine?
Allylamine.
82
What is the mechanism of Terbinafine?
Inhibits squalene epoxidase, disrupting ergosterol synthesis.
83
What is Terbinafine used for?
Dermatophyte infections, onychomycosis.
84
What are toxicities of Terbinafine?
Hepatotoxicity, taste disturbances.
85
What is the route of Terbinafine?
Topical or oral.
86
What class is Ibrexafungerp?
Triterpenoid antifungal.
87
What is the mechanism of Ibrexafungerp?
Inhibits β-1,3-glucan synthase.
88
What is Ibrexafungerp used for?
Vulvovaginal candidiasis, including resistant species.
89
What is a key feature of Ibrexafungerp?
Oral formulation with activity against echinocandin-resistant strains.
90
What class is Griseofulvin?
Mitotic spindle inhibitor.
91
What is the mechanism of Griseofulvin?
Inhibits microtubules, preventing mitosis.
92
What is Griseofulvin used for?
Dermatophyte infections.
93
What are toxicities of Griseofulvin?
Photosensitivity, hepatotoxicity.
94
What is a key feature of Griseofulvin?
Deposits in keratinized tissues (skin, hair, nails).
95
What class is Tavaborole?
Leucyl-tRNA synthetase inhibitor.
96
What is the mechanism of Tavaborole?
Inhibits fungal protein synthesis.
97
What is Tavaborole used for?
Topical treatment of onychomycosis.
98
What is a key feature of Tavaborole?
Boron-based topical antifungal.

therapeutics V (19 decks)

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