Lecture 178 Flashcards
(136 cards)
1
Q
What are fungal cell walls mainly composed of?
A
Fibrillar polysaccharides (beta-(1,3)-glucan and chitin)
2
Q
What antifungal is both amphipathic and amphoteric?
A
Amphotericin B
3
Q
What is the activity of amphotericin B?
A
Broad spectrum, mainly fungicidal
4
Q
What antifungal agent is released from liposomes upon attachment to the fungal cell wall?
A
Amphotericin B
5
Q
How is AMB administered?
A
Slow IV infusion
6
Q
What form of AMB has nonlinear kinetics and a widely varying half-life?
A
Lipid AMB
7
Q
What form of AMB requires renal dosing adjustments?
A
C-AMB
8
Q
What antifungal agent acts by binding hydrophobically to ergosterol in the fungal plasma membrane and forming pores in the membrane, causing leakage of intracellular cations and eventually leading to cell death?
A
AMB
9
Q
Mutations in what fungal genes can reduce ergosterol concentration or lead to replacement with precursor sterols, reducing AMB susceptibility?
A
Ergosterol biosynthesis genes (ERG genes)
10
Q
What is the indicated therapeutic use for AMB?
A
To treat progressive, potentially life-threatening systemic fungal infections
11
Q
What is the gold standard induction therapy for cryptococcal meningoencephalitis?
A
AMB
12
Q
What is the drug of choice for invasive mucormycosis?
A
AMB
13
Q
What is the recommended agent for treating serious fungal infections during pregnancy?
A
AMB
14
Q
What is the most common toxicity related to AMB?
A
Nephrotoxicity
15
Q
What adverse effect occurs in nearly all patients taking AMB?
A
Azotemia (high serum nitrogenous wastes)
16
Q
It is recommended to co-administer ____ with AMB to reduce the risks of nephrotoxicity?
A
Normal saline
17
Q
Anemia is an adverse effect of AMB treatment due to impaired ____
A
EPO synthesis
18
Q
Amphotericin B belongs to what class of antifungal agents?
A
Polyene antifungals
19
Q
Flucytosine belongs to what class of antifungal agents?
A
Pyrimidine analogues
20
Q
What is 5-FC?
A
Flucytosine
21
Q
Flucytosine (5-FC) is converted to cytotoxic ____ within fungal cells
A
5-fluorouracil
22
Q
What is the activity of flucytosine?
A
Narrow spectrum; fungistatic
23
Q
How is 5-FC administered?
A
Orally
24
Q
Dosing adjustments of 5-FC are required for patients with ____
A
Renal impairment
25
What antifungal agent enters fungal cells via cytosine permease transporter?
Flucytosine
26
What antifungal agent is metabolized into a toxic pyrimidine analog and then incorporated into RNA, disrupting RNA function and protein synthesis?
Flucytosine
27
Loss of fungal cytosine permease transporter results in resistance to what antifungal agent?
Flucytosine
28
Why should flucytosine always be used in combination therapy?
Resistance rapidly develops when used as monotherapy
29
Flucytosine is typically paired with ____ as combination therapy
AMB
30
What antifungal agent is often paired with AMB to treat cryptococcal meningoencephalitis and systemic/invasive candidiasis?
Flucytosine
31
N/V, diarrhea, bone marrow suppression, and elevated LFTs are adverse effects of what antifungal agent?
Flucytosine
32
Azole antifungals containing imidazoles are generally for ____ use
Topical use
33
Azole antifungals containing triazoles are generally for ____ use
Systemic use
34
What class of antifungals does ketoconazole belong to?
Imidazoles
35
What class of antifungals does clotrimazole belong to?
Imidazoles
36
What class of antifungals does miconazole belong to?
Imidazoles
37
What class of antifungals does fluconazole belong to?
Triazoles
38
What class of antifungals does itraconazole belong to?
Triazoles
39
What class of antifungals does voriconazole belong to?
Triazoles
40
What class of antifungals does posaconazole belong to?
Triazoles
41
What class of antifungals does isavuconazole belong to?
Triazoles
42
What activity do azoles have against fungi?
Predominantly fungistatic, broad spectrum
43
What azoles are available in IV form?
Fluconazole, voriconazole, posaconazole, isavuconazole
44
Itraconazole, posaconazole, and ketoconazole absorption requires ____ for absorption
Acidic environment, eat with a meal
45
What two azoles achieve therapeutic concentrations in the CNS?
Fluconazole and voriconazole
46
Most azoles are metabolized by ____
CYP3A4/CYP2C family
47
What two azoles have minimal metabolism?
Fluconazole and posaconazole
48
What azole is metabolized by CYP3A4 and UGT?
Isavuconazole
49
What azole requires adjustment for renal insufficiency?
Fluconazole
50
What two azole IV formulations contain cyclodextrin which can cause kidney toxicity?
Voriconazole and posaconazole
51
What is the broad mechanism of action of azoles?
Inhibits the synthesis of ergosterol
52
What class of antifungals blocks the heme iron in the fungal 12-alpha-demethylase, resulting in depletion of ergosterol and accumulation of toxic metabolites?
Azoles
53
What gene encodes for the fungal CYP450 enzyme 14-alpha-demethylase?
ERG11
54
Mutations in the ERG11 gene decrease binding affinity of what antifungal to 14-alpha-demethylase?
Azoles
55
Aside from gene mutations, what other mechanism might confer resistance to azoles?
Increased expression of efflux pumps
56
What is the drug of choice for dimorphic fungal infections?
Itraconazole
57
What is the first-line oral drug for vulvovaginal candidiasis?
Fluconazole
58
Fluconazole has no activity against ____ or ____
Aspergillus or Mucorales
59
What is the initial drug of choice for treating cryptococcal meningitis?
Fluconazole
60
What is the drug of choice for treating candidemia, mucocutaneous candidiasis, and coccidioidomycosis?
Fluconazole
61
What is the drug of choice for invasive Aspergillosis?
Voriconazole
62
What two azoles are the broadest spectrum?
Posaconazole and isavuconazole
63
What are the only two azoles with activity against Mucorales?
Posaconazole and isavuconazole
64
What two azoles are used for refractory invasive Aspergillosis and Mucormycosis infections or in patients with intolerance to other medications?
Posaconazole and isavuconazole
65
What two azoles are alternative treatments for Cryptococcal meningitis?
Voriconazole and posaconazole
66
What azole can be used as an alternative to Voriconazole for invasive aspergillosis if CNS/ocular toxicity is a concern?
Isavuconazole
67
What triazole is not used as prophylaxis in high-risk patients?
Fluconazole
68
What class of antifungals causes N/V, QT interval prolongation, Torsade's de Pointes, and hypersensitivity reactions?
Azoles
69
What adverse effect is most common with itraconazole but also in voriconazole and posaconazole?
Peripheral neuropathy
70
What is a relative contraindication for use of azoles?
Pregnancy, only use if benefit outweighs risk
71
What azole can specifically cause congestive heart failure, new/worsening hypertension, and moderate risk of adrenal suppression and pseudohyperaldosteronism?
Itraconazole
72
What azole is contraindicated in patients with heart failure?
Itraconazole
73
What azole can specifically cause ophthalmic effects, peripheral neuropathy, encephalopathy, hallucinations, and periostitis?
Voriconazole
74
What azole is a strong inhibitor of steroidogenesis and carries a high risk of adrenal suppression?
Ketoconazole
75
What azole has a moderate risk of adrenal suppression and pseudohyperaldosteronism?
Posaconazole
76
What causes adrenal suppression during treatment with azoles?
Inhibition of CYP enzymes involved in steroid synthesis
77
Oligospermia, gynecomastia, menstrual irregularities, and decreased libido occurring during treatment with azoles is a sign of ____
Adrenal suppression
78
Hypertension and hypokalemia during azole treatment is a sign of ____
Pseudohyperaldosteronism
79
Most azoles are strong inhibitors of ____
CYP3A4
80
What two azoles inhibit CYP2C9/2C19?
Fluconazole and voriconazole
81
What four azoles inhibit P-glycoprotein?
Itraconazole, posaconazole, isavuconazole, and ketoconazole
82
What class of antifungals does caspofungin belong to?
Echinocandins
83
What class of antifungals does micafungin belong to?
Echinocandins
84
What class of antifungals does anidulafungin belong to?
Echinocandins
85
What class of antifungals does rezafungin belong to?
Echinocandins
86
Echinocandins have potent fungicidal activity against most ____ species
Candida
87
Echinocandins have fungistatic activity against ____ species
Aspergillus
88
How are echinocandins administered?
IV
89
How are echinocandins metabolized?
Non-CYP hepatic metabolism
90
What echinocandin has non-linear elimination kinetics?
Caspofungin
91
What echinocandin has a long half-life, allowing for once weekly dosing?
Rezafungin
92
What class of antifungals inhibit the enzyme beta-(1,3)-D-glucan synthase?
Echinocandins
93
What class of antifungals inhibits beta-(1,3)-D-glucan, disrupting cell wall synthesis and integrity, leading to osmotic instability and fungal cell death?
Echinocandins
94
What type of inhibitors are echinocandins?
Noncompetitive inhibitors
95
Point mutations in FKS1 or FKS2 genes can confer resistance to what class of antifungals?
Echinocandins
96
What class of antifungals are used as second-line or salvage therapy for invasive aspergillosis?
Echinocandins
97
Echinocandins is used as empiric therapy for ____
Febrile neutropenia
98
Hypersensitivity reactions, histamine-like effects, N/V, and phlebitis at infusion sites are common adverse effects of what antifungal class?
Echinocandins
99
What relative contraindication is listed for echinocandins?
Pregnancy, only use if benefit outweighs risk
100
What echinocandin may increase levels of cyclosporine (and vice versa)?
Caspofungin
101
What echinocandin increases tacrolimus levels?
Caspofungin
102
What echinocandin increases levels of sirolimus and nifedipine?
Micafungin
103
What class of antifungals may decrease therapeutic effects of saccharomyces boulardii (probiotic yeast)?
Echinocandins
104
What class of antifungals does terbinafine belong to?
Allylamines
105
What is the activity of terbinafine?
Broad spectrum fungicidal, activate against dermatophytes and Candida
106
What antifungal accumulates in sebum, hair, skin, and nails?
Terbinafine
107
How is terbinafine metabolized?
CYP metabolism
108
Terbinafine should be avoided in patients with marked ____ or ____ impairment
Renal or hepatic impairment
109
What antifungal noncompetitively inhibits the fungal enzyme squalene epoxidase?
Terbinafine
110
Terbinafine blocks the conversion of squalene to ____
Lanosterol
111
What antifungal causes inhibition of squalene epoxidase, ultimately resulting in ergosterol depletion and accumulation of toxic levels of intracellular squalene?
Terbinafine
112
Mutations in the squalene epoxidase gene (SQLE) may confer resistance to what antifungal?
Terbinafine
113
What is the drug of choice for treating onychomycosis (fungal nail infection)?
Oral terbinafine
114
How long does oral terbinafine therapy treatment for onychomycosis last?
Months
115
What oral antifungal is used to treat tinea capitis and other dermatophyte infections refractory to topical treatment?
Terbinafine
116
What topical antifungal is used to treat cutaneous dermatophytosis and cutaneous candidiasis?
Terbinafine
117
Dyspepsia, nausea, diarrhea, headache, taste/smell disturbances, and hypersensitivity reactions are adverse effects of what antifungal?
Terbinafine
118
What contraindications are listed for terbinafine?
Chronic/active liver disease and/or pregnancy
119
Terbinafine is a strong inhibitor of ____
CYP2D6
120
What antifungal agent is derived from Penicillium mold?
Griseofulvin
121
What is the activity of griseofulvin?
Fungistatic against dermatophytes only
122
How is griseofulvin administered?
Orally
123
What antifungal agent requires specific formulations and administration with a high fat meal for adequate absorption?
Griseofulvin
124
What antifungal agent deposits and concentrates in keratin precursor cells?
Griseofulvin
125
What antifungal agent is taken up by dermatophytes after binding to newly formed keratin in precursor cells?
Griseofulvin
126
What antifungal binds to fungal tubulin and disrupts microtubule function and inhibits fungal mitosis in metaphase?
Griseofulvin
127
Mutations in tubulin genes of fungi confer resistance to what antifungal?
Griseofulvin
128
What is the drug of choice for treating tinea capitis in children?
Griseofulvin
129
Headache, dizziness, GI upset, photosensitivity, and rash are adverse effects of what antifungal?
Griseofulvin
130
What are contraindications for griseofulvin therapy?
Pregnancy, porphyria, hepatic failure
131
Griseofulvin is a CYP ____
Inducer
132
Griseofulvin and alcohol may cause what type of reaction?
Disulfiram-like reaction
133
Nystatin belongs to what class of antifungals?
Polyene antibiotic (like AMB)
134
What is the activity of nystatin?
Candida species only
135
What is the primary use of nystatin?
Topical suppression of local candida infections (oral suspension, vaginal tablets, cream)
136
What class of antifungals does clotrimazole belong to?
Topical azoles
