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MF2 Pharmacology > Antifungals > Flashcards

Antifungals Flashcards

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
Q

Formulation of Amphotericin B that reduces nephrotoxicity but prolongs infusion reaction

A

Liposomal formulations

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26
Q

Liposomal formulations of this drug reduce nephrotoxicity but prolong infusion reaction

A

Amphotericin B

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27
Q

Amphotericin B liposomal formulations reduce this

A

Reduce nephrotoxicity
but prolong infusion reaction

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28
Q

Amphotericin B liposomal formulations reduce nephrotoxicity but prolong this

A

Infusion reaction

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29
Q

Antifungal indicated for a wide range of fungal infections, commonly for Candida infections, Cryptococcosis, Sporotrichosis and other dangerous systemic fungal infections

A

Azoles

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30
Q

Antifungals that inhibits fungal lanosterol 14-alpha-demethylase (CYP51A1) thereby inhibiting fungal ergosterol synthesis
Increases fungal permeability by same mechanism

A

Azoles

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31
Q

MOA of Azoles

A

Inhibits fungal lanosterol 14-alpha-demethylase (CYP51A1) thereby inhibiting fungal ergosterol synthesis (fungistatic)
Increases fungal permeability by same mechanism

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32
Q

Azoles inhibit this enzyme

A

lanosterol 14-alpha-demethylase (CYP51A1)
(involved in fungal ergosterol synthesis)

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33
Q

Azoles inhibit fungal lanosterol 14-alpha-demethylase, aka this enzyme

A

CYP51A1

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34
Q

Azoles inhibit CYP51A1, aka this enzyme

A

lanosterol 14-alpha-demethylase

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35
Q

Azoles inhibit fungal lanosterol 14-alpha-demethylase (CYP51A1), thereby inhibiting synthesis of this

A

Ergosterol

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36
Q

Spectrum of Azoles

A

Broad spectrum antifungal activity; resistance is an emerging problem

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37
Q

Absorption of Azoles require this

A

Acidic environment (except fluconazole)

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38
Q

Azoles require acid environment for oral absorption, with this exception

A

Fluconazole

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39
Q

Fluconazole is an exception for this requirement of oral absorption of Azoles

A

Does NOT require acid environment

40
Q

Hepatic changes, prolonged QT interval, and endocrine effects are adverse effects of these

41
Q

Prolonged QT interval, leading to possible arrhythmia is a characteristic adverse effect of this

42
Q

High doses of this drug are linked to endocrine effects linked to disruption of CYP action in steroid synthesis, altered sex hormone levels

43
Q

High doses of Azoles are linked to this adverse effect

A

Endocrine effects
Linked to disruption of CYP action in steroid synthesis, altered sex hormone levels

44
Q

Endocrine effects as a result of high doses of Azoles are linked to this

A

Disruption of CYP action in steroid synthesis

45
Q

Azoles should be avoided with drugs that do this

A

Decrease gastric acid secretion
Will slow azole dissolution and absorption
Exception is fluconazole

46
Q

Antifungals whose use should be avoided with drugs that decrease gastric acid secretion

47
Q

Why should azole use be avoided with drugs that decrease gastric acid secretion?

A

Because these will slow azole dissolution and absorption (except for fluconazole)
Azoles require acid environment for absorption

48
Q

With use of azoles, be alert for possible drug-drug interactions resulting from this

A

CYP inhibition

49
Q

MOA of echinocandins

A

Inhibit Beta-1,3-glucan formation to reduce cell wall integrity

50
Q

Antifungals that Inhibit Beta-1,3-glucan formation to reduce cell wall integrity

A

Echinocandins

51
Q

Echinocandins inhibit formation of this

A

Beta-1,3-glucan
Reduces cell wall integrity

52
Q

Echinocandins inhibit beta-1,3-glucan formation, which has this effect

A

Reduce cell wall integrity
Results in cell wall instability and death (fungicidal)

53
Q

Antifungals Indicated for invasive Candidiasis, esophageal Candidiasis, candidemia and others

A

Echinocandins

54
Q

Transient hepatotoxicity (monitor liver markers) and flushing are adverse effects of these

A

Echinocandins

55
Q

Antifungal that is a prodrug converted by fungal enzymes

A

Flucytosine

56
Q

MOA of Flucytosine

A

Prodrug converted to 5-FU by fungal cytosine deaminase
Inhibits protein and DNA synthesis

57
Q

What provides selective toxicity for flucytosine?

A

Requirement of fungal cytosine deaminase

58
Q

Flucytosine is activated by fungal cytosine deaminase to this

A

5-fluorouracil

59
Q

Flucytosine is activated by this to 5-fluorouracil

A

Fungal cytosine deaminase

60
Q

Antifungal that is activated by fungal cytosine deaminase to 5-FU

A

Flucytosine

61
Q

Antifungal that be activated and incorporated into fungal RNA to inhibit protein synthesis, or converted to nucleotide form to inhibit DNA synthesis

A

Flucytosine

62
Q

Flucytosine toxicity is mainly due to this

A

Fungal release of 5-FU

63
Q

Antifungal whose toxicity is mainly due to fungal release of 5-FU

A

Flucytosine

64
Q

Antifungal with black box warning urging caution when used in patients with renal impairment

A

Flucytosine

65
Q

Flucytosine black box warning urges caution when used in patients with this

A

Renal impairment

66
Q

Flucytosine bone marrow depression occurs from this, a powerful and toxic anticancer drug, released following fungal death

A

5-fluorouracil

67
Q

Antifungal with bone marrow depression and hepatotoxicity as adverse effects

A

Flucytosine

68
Q

This is an adverse effect of flucytosine that occurs from 5-FU, a powerful and toxic anticancer drug, released following fungal death

A

Bone marrow depression

69
Q

Bone marrow suppression is a characteristic adverse effect of this antifungal

A

Flucytosine

70
Q

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

A

Flucytosine and Amphotericin B combination

71
Q

Antifungal indicated for Candida infections of skin, vagina, mouth and esophagus

72
Q

Antifungal with MOA similar to amphotericin B in that it binds to sterols in the fungal membrane to cause leaks

73
Q

MOA of nystatin

A

Similar to that of amphotericin B in that it binds to sterols in the fungal membrane to cause leaks

74
Q

Oral/esophageal fungal infections

75
Q

Antifungal used topically to avoid severe systemic toxicity and does not produce systemic levels of any significance

76
Q

Antifungal often used in “swish and swallow” treatment of thrush

77
Q

Systemic or topically administered anti-fungal for dermatophytic infections

A

terbinafine and Naftifine

78
Q

Antifungal that inhibits squalene epoxidase, a key enzyme in sterol synthesis in fungal, depleting ergosterol

A

Terbinafine and Naftifine

79
Q

MOA of Terbinafine and Naftifine

A

Inhibits squalene epoxidase, depleting ergosterol

80
Q

Terbinafine and Naftifine inhbit this

A

Squalene epoxidase
(depleting ergosterol)

81
Q

Squalene epoxidase is involved in the synthesis of this

A

Ergosterol

82
Q

Naftifine uses this administration only

83
Q

Terbinafine or Naftifine:
Topical only

84
Q

Terbinafine or Naftifine:
Oral and topical formulations

A

Terbinafine

85
Q

Antifungals Indicated for Trichophyton skin and nail infections (Tinea pedis)

A

Terbinafine and Naftifine

86
Q

Hepatotoxicity (rarely severe) and taste distortion (dysgeusia), rarely severe, are adverse effects of this

A

Terbinafine and Naftifine

87
Q

Taste distortion is a characteristic adverse effect of this

A

Terbinafine and Naftifine

88
Q

Antifungal that inhibits microtubule functions, especially mitotic spindle formation, inhibiting mitosis and increasing production of multinucleate cells

A

Griseofulvin

89
Q

MOA of Griseofulvin

A

Inhibits microtubule functions
Inhibits mitosis and increases production of multinucleate cells

90
Q

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

A

Griseofulvin

91
Q

Oral solubility of Griseofulvin is improved by this

A

Microsize or ultramicrosize preparations
And by taken whole or crushed with a fatty meal

92
Q

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

A

Griseofulvin

93
Q

Why does Griseofulvin concentrate in fat and skeletal muscle, also skin, hair, nails?

A

Binds to keratinocyte precursor cells and is incorporated into new keratin

94
Q

Griseofulvin concentrates in fat and skeletal muscle because it binds to these

A

Keratinocyte precursor cells
Is incorporated into new keratin

95
Q

Elimination of Griseofulvin

A

Excreted in the urine, feces, and perspiration (sweat carries drug to skin)

96
Q

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

A

Griseofulvin

97
Q

Griseofulvin use triggers a disulfiram-like reaction in combination with this

MF2 Pharmacology (14 decks)

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