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MF2 Pharmacology > Antifungals > Flashcards

Antifungals Flashcards

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1
Q

Many antifungals are moderate to strong inhibitors of this

A

CYP3A4

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2
Q

Amphotericin B, the -azoles, the -fungins, and Flucytosine (5-fluorocystine) treat these kind of fungi

A

Subcutaneous/systemic

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3
Q

Griseofulvin, Nystatin, Terbinafine and Naftifine treat this type of fungi

A

Cutaneous

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4
Q

2 enzymes involved in fungal ergosterol synthesis that are targets for antifungals

A

Squalene epoxidase
14-alpha-demethylase (a CYP450 molecule)

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5
Q

Amphotericin B, Azoles, Echinocandins and Flucytosine treat this type of mycoses

A

Systemic

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6
Q

Natural polyene antifungal produced by Streptomyces bacteria

A

Amphotericin B

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7
Q

Amphotericin B is a natural polyene antifungal produced by this

A

Streptomyces bacteria

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8
Q

Streptomyces bacteria produce this antifungal

A

Amphotericin B

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9
Q

Antifungal effective against wide range of fungi, including Candida albicans, Coccidioides immitis, and many strains of Aspergillus

A

Amphotericin B

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10
Q

Antifungal that binds to fungal membrane component ergosterol
Alters fungal cellular permeability, a pore former mechanism

A

Amphotericin B

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11
Q

MOA of Amphotericin B

A

Binds to fungal membrane component ergosterol
Alters fungal cellular permeability = a pore former

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12
Q

Amphotericin B binds to this fungal component

A

Membrane component ergosterol

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13
Q

Primarily administration route of Amphotericin B

A

IV
(inhalation and oral routes possible)

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14
Q

Does Amphotericin B penetrate the meninges?

A

No - poor penetration into most compartmented fluids (meningeal, humoral, etc.)

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15
Q

Biotransformation rate of Amphotericin B

A

Slow
Half life can vary considerably

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16
Q

Half life of Amphotericin B

A

Can vary considerably; 24 hours to 15 days (depending on the state of renal function, number of doses, tissue storage)

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17
Q

Common adverse effects of Amphotericin B are related to this

A

Infusion related
Headache, fever, chills, hypotension, nausea/vomiting and tachypnea

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18
Q

Infusion related adverse effects of Amphotericin B (headache, fever, chills, hypotension, nausea/comiting and tachypnea) can be managed by premedicating with these 3

A

Ibuprofen, Antihistamines, Steroids (hydrocortisone)

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19
Q

Pretreating Amphotericin B with ibuprofen, antihistamines, and steroids is a method of managing this

A

Infusion related adverse effects (headache, fever, chills, hypotension, nausea/vomiting, tachypnea)

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20
Q

Severe chills as a result of Amphotericin B can be treated with this

A

Meperidine

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21
Q

Meperidine can treat this adverse effect of Amphotericin B

A

Chills, if severe
infusion-related

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22
Q

Principle adverse effect associated with long-term treatment of Amphotericin B

A

Nephrotoxicity

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23
Q

Nephrotoxicity is the principle adverse effect associated with long-term treatment of this antifungal

A

Amphotericin B

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24
Q

Antifungal with a black box that states it should be used in serious invasive fungal infections only and at safe dosages

A

Amphotericin B

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25
Formulation of Amphotericin B that reduces nephrotoxicity but prolongs infusion reaction
Liposomal formulations
26
Liposomal formulations of this drug reduce nephrotoxicity but prolong infusion reaction
Amphotericin B
27
Amphotericin B liposomal formulations reduce this
Reduce nephrotoxicity but prolong infusion reaction
28
Amphotericin B liposomal formulations reduce nephrotoxicity but prolong this
Infusion reaction
29
Antifungal indicated for a wide range of fungal infections, commonly for Candida infections, Cryptococcosis, Sporotrichosis and other dangerous systemic fungal infections
Azoles
30
Antifungals that inhibits fungal lanosterol 14-alpha-demethylase (CYP51A1) thereby inhibiting fungal ergosterol synthesis Increases fungal permeability by same mechanism
Azoles
31
MOA of Azoles
Inhibits fungal lanosterol 14-alpha-demethylase (CYP51A1) thereby inhibiting fungal ergosterol synthesis (fungistatic) Increases fungal permeability by same mechanism
32
Azoles inhibit this enzyme
lanosterol 14-alpha-demethylase (CYP51A1) (involved in fungal ergosterol synthesis)
33
Azoles inhibit fungal lanosterol 14-alpha-demethylase, aka this enzyme
CYP51A1
34
Azoles inhibit CYP51A1, aka this enzyme
lanosterol 14-alpha-demethylase
35
Azoles inhibit fungal lanosterol 14-alpha-demethylase (CYP51A1), thereby inhibiting synthesis of this
Ergosterol
36
Spectrum of Azoles
Broad spectrum antifungal activity; resistance is an emerging problem
37
Absorption of Azoles require this
Acidic environment (except fluconazole)
38
Azoles require acid environment for oral absorption, with this exception
Fluconazole
39
Fluconazole is an exception for this requirement of oral absorption of Azoles
Does NOT require acid environment
40
Hepatic changes, prolonged QT interval, and endocrine effects are adverse effects of these
Azoles
41
Prolonged QT interval, leading to possible arrhythmia is a characteristic adverse effect of this
Azoles
42
High doses of this drug are linked to endocrine effects linked to disruption of CYP action in steroid synthesis, altered sex hormone levels
Azoles
43
High doses of Azoles are linked to this adverse effect
Endocrine effects Linked to disruption of CYP action in steroid synthesis, altered sex hormone levels
44
Endocrine effects as a result of high doses of Azoles are linked to this
Disruption of CYP action in steroid synthesis
45
Azoles should be avoided with drugs that do this
Decrease gastric acid secretion Will slow azole dissolution and absorption Exception is fluconazole
46
Antifungals whose use should be avoided with drugs that decrease gastric acid secretion
Azoles
47
Why should azole use be avoided with drugs that decrease gastric acid secretion?
Because these will slow azole dissolution and absorption (except for fluconazole) Azoles require acid environment for absorption
48
With use of azoles, be alert for possible drug-drug interactions resulting from this
CYP inhibition
49
MOA of echinocandins
Inhibit Beta-1,3-glucan formation to reduce cell wall integrity
50
Antifungals that Inhibit Beta-1,3-glucan formation to reduce cell wall integrity
Echinocandins
51
Echinocandins inhibit formation of this
Beta-1,3-glucan Reduces cell wall integrity
52
Echinocandins inhibit beta-1,3-glucan formation, which has this effect
Reduce cell wall integrity Results in cell wall instability and death (fungicidal)
53
Antifungals Indicated for invasive Candidiasis, esophageal Candidiasis, candidemia and others
Echinocandins
54
Transient hepatotoxicity (monitor liver markers) and flushing are adverse effects of these
Echinocandins
55
Antifungal that is a prodrug converted by fungal enzymes
Flucytosine
56
MOA of Flucytosine
Prodrug converted to 5-FU by fungal cytosine deaminase Inhibits protein and DNA synthesis
57
What provides selective toxicity for flucytosine?
Requirement of fungal cytosine deaminase
58
Flucytosine is activated by fungal cytosine deaminase to this
5-fluorouracil
59
Flucytosine is activated by this to 5-fluorouracil
Fungal cytosine deaminase
60
Antifungal that is activated by fungal cytosine deaminase to 5-FU
Flucytosine
61
Antifungal that be activated and incorporated into fungal RNA to inhibit protein synthesis, or converted to nucleotide form to inhibit DNA synthesis
Flucytosine
62
Flucytosine toxicity is mainly due to this
Fungal release of 5-FU
63
Antifungal whose toxicity is mainly due to fungal release of 5-FU
Flucytosine
64
Antifungal with black box warning urging caution when used in patients with renal impairment
Flucytosine
65
Flucytosine black box warning urges caution when used in patients with this
Renal impairment
66
Flucytosine bone marrow depression occurs from this, a powerful and toxic anticancer drug, released following fungal death
5-fluorouracil
67
Antifungal with bone marrow depression and hepatotoxicity as adverse effects
Flucytosine
68
This is an adverse effect of flucytosine that occurs from 5-FU, a powerful and toxic anticancer drug, released following fungal death
Bone marrow depression
69
Bone marrow suppression is a characteristic adverse effect of this antifungal
Flucytosine
70
Antifungal combination with synergistic MOA that can be used for severe candida and cryptococcal infections Both drugs can be used at lower concentrations to reduce toxicity of both agents
Flucytosine and Amphotericin B combination
71
Antifungal indicated for Candida infections of skin, vagina, mouth and esophagus
Nystatin
72
Antifungal with MOA similar to amphotericin B in that it binds to sterols in the fungal membrane to cause leaks
Nystatin
73
MOA of nystatin
Similar to that of amphotericin B in that it binds to sterols in the fungal membrane to cause leaks
74
Oral/esophageal fungal infections
Thrush
75
Antifungal used topically to avoid severe systemic toxicity and does not produce systemic levels of any significance
Nystatin
76
Antifungal often used in "swish and swallow" treatment of thrush
Nystatin
77
Systemic or topically administered anti-fungal for dermatophytic infections
terbinafine and Naftifine
78
Antifungal that inhibits squalene epoxidase, a key enzyme in sterol synthesis in fungal, depleting ergosterol
Terbinafine and Naftifine
79
MOA of Terbinafine and Naftifine
Inhibits squalene epoxidase, depleting ergosterol
80
Terbinafine and Naftifine inhbit this
Squalene epoxidase (depleting ergosterol)
81
Squalene epoxidase is involved in the synthesis of this
Ergosterol
82
Naftifine uses this administration only
Topical
83
Terbinafine or Naftifine: Topical only
Naftifine
84
Terbinafine or Naftifine: Oral and topical formulations
Terbinafine
85
Antifungals Indicated for Trichophyton skin and nail infections (Tinea pedis)
Terbinafine and Naftifine
86
Hepatotoxicity (rarely severe) and taste distortion (dysgeusia), rarely severe, are adverse effects of this
Terbinafine and Naftifine
87
Taste distortion is a characteristic adverse effect of this
Terbinafine and Naftifine
88
Antifungal that inhibits microtubule functions, especially mitotic spindle formation, inhibiting mitosis and increasing production of multinucleate cells
Griseofulvin
89
MOA of Griseofulvin
Inhibits microtubule functions Inhibits mitosis and increases production of multinucleate cells
90
Antifungal with oral absorption, limited by poor solubility, improved by microsize or ultramicrosize preparations/tablets and by taken whole or crushed with a fatty meal
Griseofulvin
91
Oral solubility of Griseofulvin is improved by this
Microsize or ultramicrosize preparations And by taken whole or crushed with a fatty meal
92
Antifungal that is concentrated in fat and skeletal muscle, but also skin, hair, nails, because it binds to keratinocyte precursor cells and is incorporated into new keratin
Griseofulvin
93
Why does Griseofulvin concentrate in fat and skeletal muscle, also skin, hair, nails?
Binds to keratinocyte precursor cells and is incorporated into new keratin
94
Griseofulvin concentrates in fat and skeletal muscle because it binds to these
Keratinocyte precursor cells Is incorporated into new keratin
95
Elimination of Griseofulvin
Excreted in the urine, feces, and perspiration (sweat carries drug to skin)
96
Transient headache (~15%), cognitive disruptions, considered teratogenic and carcinogenic, and triggers a disulfiram-like reaction in combination with alcohol are adverse effects of this antifungal
Griseofulvin
97
Griseofulvin use triggers a disulfiram-like reaction in combination with this
Alcohol

MF2 Pharmacology (14 decks)

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