Antifungals Flashcards
1
Q
What are the three classifications of fungal infections?
A
Superficial/cutaneous, subcutaneous, and systemic/invasive.
2
Q
What is the mechanism of action of polyenes like amphotericin B?
A
Bind ergosterol in fungal membranes, form pores, cause cell leakage.
3
Q
Are polyenes fungistatic or fungicidal?
A
Fungicidal.
4
Q
How is amphotericin B administered?
A
IV for systemic infections.
5
Q
What are the main adverse effects of amphotericin B?
A
Nephrotoxicity and infusion reactions.
6
Q
How do lipid formulations of amphotericin B help?
A
They reduce nephrotoxicity and infusion toxicity.
7
Q
What is the mechanism of action of azoles?
A
Inhibit 14-α-demethylase (CYP450), blocking ergosterol synthesis.
8
Q
Are azoles fungistatic or fungicidal?
A
Fungistatic.
9
Q
What are key azoles used systemically?
A
Fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole.
10
Q
Why do azoles have drug-drug interactions?
A
They inhibit and are metabolized by liver CYP450 enzymes.
11
Q
What is the mechanism of action of terbinafine?
A
Inhibits squalene epoxidase, causing squalene accumulation.
12
Q
Is terbinafine fungicidal or fungistatic?
A
Fungicidal.
13
Q
What types of infections does terbinafine treat?
A
Dermatophytes, nail and skin infections.
14
Q
What is the mechanism of action of echinocandins?
A
Inhibit β(1-3)-glucan synthase in the fungal cell wall.
15
Q
Are echinocandins fungicidal or fungistatic?
A
Fungicidal.
16
Q
How are echinocandins administered?
A
IV only.
17
Q
What makes echinocandins selective for fungi?
A
Mammals do not have β(1-3)-glucan synthase.
18
Q
What is the mechanism of action of flucytosine?
A
Converted to 5-FU → inhibits thymidylate synthase → inhibits DNA/RNA synthesis.
19
Q
What are key properties of flucytosine?
A
Oral only, renally eliminated, narrow therapeutic window.
20
Q
Why is flucytosine combined with amphotericin B?
A
To reduce resistance and increase efficacy.
21
Q
What is the mechanism of action of griseofulvin?
A
Disrupts microtubules, inhibits mitosis.
22
Q
What does griseofulvin treat?
A
Dermatophyte infections of skin, hair, and nails.
23
Q
What is the mechanism of action of tavaborole?
A
Inhibits leucyl-tRNA synthetase, blocking protein synthesis.
24
Q
What is tavaborole used for?
A
Topical treatment of onychomycosis.
25
What are mechanisms of azole resistance?
Target alteration, efflux pumps, enzyme upregulation, bypass pathways.
26
How do fungi become resistant to polyenes?
Reduce ergosterol content.
27
Which antifungal is preferred systemically during pregnancy?
Amphotericin B.
28
Which antifungals should be avoided during pregnancy?
Fluconazole (high dose), azoles, flucytosine, griseofulvin, voriconazole.
29
Are topical antifungals safe in pregnancy?
Yes.
30
What is the main difference between fungal and human cell membranes?
Fungal membranes contain ergosterol, while human membranes contain cholesterol.
31
How is the difference in membrane sterols exploited in antifungal therapy?
Drugs like amphotericin B and azoles target ergosterol or its synthesis, which is absent in human cells.
32
What enzyme is inhibited by allylamines?
Squalene epoxidase.
33
What enzyme is inhibited by azole antifungals?
14-alpha-demethylase (a CYP450 enzyme).
34
What class do amphotericin B and nystatin belong to?
Polyenes.
35
What is the mechanism of action of amphotericin B and nystatin?
Bind to ergosterol in fungal membranes, forming pores that lead to cell death.
36
Why are amphotericin B and nystatin selective for fungi?
They bind ergosterol, which is not present in human membranes.
37
What class does terbinafine belong to?
Allylamine.
38
What is the mechanism of action of terbinafine?
Inhibits squalene epoxidase, disrupting ergosterol synthesis and causing toxic squalene accumulation.
39
What class do ketoconazole, itraconazole, fluconazole, voriconazole, and isavuconazole belong to?
Azoles.
40
What is the mechanism of action of azole antifungals?
Inhibit 14-alpha-demethylase, blocking ergosterol synthesis.
41
What is the structural significance of the azole functional group?
The azole ring coordinates with iron in the CYP450 enzyme, inhibiting its function.
42
What class does oteseconazole belong to?
Azole.
43
What class do caspofungin, micafungin, and anidulafungin belong to?
Echinocandins.
44
What is the mechanism of action of echinocandins?
Inhibit β(1-3)-glucan synthase, weakening the fungal cell wall.
45
What is unique about rezafungin?
It is a long-acting echinocandin with once-weekly IV dosing.
46
What is the mechanism of action of flucytosine?
Converted to 5-FU in fungal cells, inhibiting thymidylate synthase and disrupting DNA synthesis.
47
Why is flucytosine selective for fungi?
Human cells cannot convert it to the active 5-FU form.
48
What reaction does thymidylate synthase catalyze?
Conversion of dUMP to dTMP, a step in DNA synthesis.
49
How does flucytosine inhibit thymidylate synthase?
5-FdUMP (active metabolite) acts as a suicide inhibitor of thymidylate synthase.
50
What class does ibrexafungerp belong to?
Glucan synthase inhibitor (triterpenoid antifungal).
51
What is the mechanism of action of ibrexafungerp?
Inhibits β(1-3)-glucan synthase enzyme, depleting cell wall glucans.
52
What class does tavaborole belong to?
Leucyl-tRNA synthetase inhibitor.
53
What is the mechanism of action of tavaborole?
Inhibits LeuRS, blocking fungal protein synthesis.
54
What are the major toxicities of amphotericin B?
Nephrotoxicity and infusion-related reactions.
55
Why is flucytosine often combined with amphotericin B?
To improve efficacy and reduce resistance.
56
How do azoles interact with cytochrome P450 enzymes?
They inhibit CYP450s, affecting metabolism of other drugs and causing drug interactions.
57
What class does Amphotericin B belong to?
Polyenes
58
What is the mechanism of action of Amphotericin B?
Binds to ergosterol, forms pores in membrane
59
What is Amphotericin B used for?
Severe systemic fungal infections
60
What are key notes about Amphotericin B?
IV only; nephrotoxic; lipid formulations reduce toxicity
61
What class does Nystatin belong to?
Polyenes
62
What is the mechanism of action of Nystatin?
Same as amphotericin B
63
What is Nystatin used for?
Superficial candidiasis
64
What are key notes about Nystatin?
Topical only; too toxic for systemic use
65
What class does Terbinafine belong to?
Allylamines
66
What is the mechanism of action of Terbinafine?
Inhibits squalene epoxidase
67
What is Terbinafine used for?
Dermatophyte infections, onychomycosis
68
What are key notes about Terbinafine?
Fungicidal; topical and oral forms
69
What class does Naftifine belong to?
Allylamines
70
What is the mechanism of action of Naftifine?
Inhibits squalene epoxidase
71
What is Naftifine used for?
Tinea infections
72
What are key notes about Naftifine?
Topical only
73
What class does Butenafine belong to?
Allylamines
74
What is the mechanism of action of Butenafine?
Inhibits squalene epoxidase
75
What is Butenafine used for?
Tinea infections
76
What are key notes about Butenafine?
Topical only
77
What class does Tolnaftate belong to?
Thiocarbamate
78
What is the mechanism of action of Tolnaftate?
Inhibits squalene epoxidase
79
What is Tolnaftate used for?
Tinea infections
80
What are key notes about Tolnaftate?
Topical only
81
What class does Ketoconazole belong to?
Imidazole (Azole)
82
What is the mechanism of action of Ketoconazole?
Inhibits 14-alpha-demethylase (CYP450)
83
What is Ketoconazole used for?
Topical fungal infections
84
What are key notes about Ketoconazole?
Strong CYP3A4 inhibitor; systemic use limited by toxicity
85
What class does Fluconazole belong to?
Triazole
86
What is the mechanism of action of Fluconazole?
Inhibits 14-alpha-demethylase
87
What is Fluconazole used for?
Candida, Cryptococcus
88
What are key notes about Fluconazole?
Renally cleared; minimal CYP interaction
89
What class does Itraconazole belong to?
Triazole
90
What is the mechanism of action of Itraconazole?
Inhibits 14-alpha-demethylase
91
What is Itraconazole used for?
Histoplasmosis, Blastomycosis
92
What are key notes about Itraconazole?
CYP3A4 substrate; needs acid for absorption
93
What class does Voriconazole belong to?
Triazole
94
What is the mechanism of action of Voriconazole?
Inhibits 14-alpha-demethylase
95
What is Voriconazole used for?
Aspergillosis
96
What are key notes about Voriconazole?
Visual disturbances; CYP2C19 metabolism
97
What class does Posaconazole belong to?
Triazole
98
What is the mechanism of action of Posaconazole?
Inhibits 14-alpha-demethylase
99
What is Posaconazole used for?
Prophylaxis in immunocompromised
100
What are key notes about Posaconazole?
Requires high-fat meal; broad spectrum
101
What class does Isavuconazole belong to?
Triazole
102
What is the mechanism of action of Isavuconazole?
Inhibits 14-alpha-demethylase
103
What is Isavuconazole used for?
Invasive aspergillosis, mucormycosis
104
What are key notes about Isavuconazole?
Prodrug (isavuconazonium); long half-life
105
What class does Oteseconazole belong to?
Triazole
106
What is the mechanism of action of Oteseconazole?
Inhibits 14-alpha-demethylase
107
What is Oteseconazole used for?
Vulvovaginal candidiasis
108
What are key notes about Oteseconazole?
New; few adverse effects
109
What class does Caspofungin belong to?
Echinocandin
110
What is the mechanism of action of Caspofungin?
Inhibits β(1-3)-glucan synthase
111
What is Caspofungin used for?
Invasive candidiasis, aspergillosis
112
What are key notes about Caspofungin?
IV only; minimal interactions
113
What class does Micafungin belong to?
Echinocandin
114
What is the mechanism of action of Micafungin?
Inhibits β(1-3)-glucan synthase
115
What is Micafungin used for?
Candidiasis prophylaxis
116
What are key notes about Micafungin?
Fewer side effects
117
What class does Anidulafungin belong to?
Echinocandin
118
What is the mechanism of action of Anidulafungin?
Inhibits β(1-3)-glucan synthase
119
What is Anidulafungin used for?
Esophageal and invasive candidiasis
120
What are key notes about Anidulafungin?
Longest half-life; no CYP metabolism
121
What class does Rezafungin belong to?
Echinocandin
122
What is the mechanism of action of Rezafungin?
Inhibits β(1-3)-glucan synthase
123
What is Rezafungin used for?
Candidiasis
124
What are key notes about Rezafungin?
Once-weekly IV; long half-life
125
What class does Flucytosine belong to?
Pyrimidine analog
126
What is the mechanism of action of Flucytosine?
Converted to 5-FU → inhibits thymidylate synthase
127
What is Flucytosine used for?
Cryptococcal meningitis (with amphotericin B)
128
What are key notes about Flucytosine?
Oral; narrow therapeutic window; renally cleared
129
What class does Ibrexafungerp belong to?
Triterpenoid
130
What is the mechanism of action of Ibrexafungerp?
Inhibits β(1-3)-glucan synthase
131
What is Ibrexafungerp used for?
Vulvovaginal candidiasis
132
What are key notes about Ibrexafungerp?
Oral; new class
133
What class does Griseofulvin belong to?
Microtubule inhibitor
134
What is the mechanism of action of Griseofulvin?
Inhibits mitosis by binding microtubules
135
What is Griseofulvin used for?
Dermatophytes (skin, hair, nails)
136
What are key notes about Griseofulvin?
Oral; binds keratin
137
What class does Tavaborole belong to?
Leucyl-tRNA synthetase inhibitor
138
What is the mechanism of action of Tavaborole?
Inhibits fungal protein synthesis
139
What is Tavaborole used for?
Onychomycosis
140
What are key notes about Tavaborole?
Topical; boron-based
