Antifungals Flashcards

1
Q

What is the infection that sporothrix schenckii?

A

Cutaneous cellulitis

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2
Q

Where is blastomycosis usually found?

A

Southwest

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3
Q

What disease does aspergillus usually cause, and in whom?

A

Pulmonary disease in immunodeficient individuals

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4
Q

What is the leading cause of fungal meningitis?

A

Cryptococcus neoformans

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5
Q

India ink stain = ?

A

Cryptococcus neoformans

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6
Q

What are the three fungi that are responsible for onychomycosis?

A

Trichophyton
Epidermophyton
Microsporum

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7
Q

What is the chemical that fungi use in place of cholesterol in their cell membranes?

A

Ergosterol and ergosterol

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8
Q

What is the in the cell wall of fungi that makes them easier to target?

A

Glucans

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9
Q

What are the two polyenes?

A

Amp B

Nystatin

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10
Q

What are the azoles?

A
Ketoconazole
Fluconazole
Itraconazole
Voriconazole
Posaconazole
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11
Q

What is the one nucleoside analog that is used for fungal infections?

A

5FU

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12
Q

What are the three echinocandins used in fungal infections?

A

caspofungin
Micafungin
Anidulafungin

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13
Q

What are the two allylamines used for fungal infections?

A

Terbinafine

Naftifine

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14
Q

What is the one microtubule inhibitor used to treat fungal infections?

A

Griseofulvin

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15
Q

Which antifungal drugs act systemically?

A

Amp B
Azoles
Flucytosine
Echinocandins

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16
Q

Which antifungal drug has the broadest spectrum of activity?

A

Amp B

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17
Q

What is the MOA of Amp B? Is this fungicidal or fungistatic?

A

Binds to ergosterol in fungal cell membrane, and alters membrane permeability

fungicidal

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18
Q

What is the recommended treatment for disseminated fungal infections?

A

Amp B

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19
Q

What is the treatment of choice for cryptococcal meningitis?

A

Amp B

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20
Q

What are the two mycomycoses? ssx?

A

Rhizopus and Absidia

Infection s of sinus of DM pts and cause cerebral infx

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21
Q

How is Amp B resistance brought about?

A

membrane ergosterol concentration is decreased or if sterol target is modified

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22
Q

Amp B is nearly insoluble in water. How, then, is it administered IV?

A

Complexed with a bil salt

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23
Q

Which tissue can Amp B not penetrate well?

A

CNS

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24
Q

What are the major side effects of Amp B administration?

A

Infusion site pain, fever, chills

Nephrotoxic (d/t decreased renal perfusion)

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25
Q

How does encasing amp B in a lipid micelle reduce its toxicity?

A

the lipids have an affinity between that of fungal ergosterol and human cholesterol. This reduces non-specific binding to human cell membranes

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26
Q

What are the two types of azoles?

A

imidiazoles

Triazoles

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27
Q

What are the three imidazoles? What are these primarily used for now?

A

Ketoconazole
Miconazole
Clotrimazole

Topical infxs

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28
Q

What are the four triazoles?

A

Fluconazole
Itraconazole
Voriconazole
Posaconazole

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29
Q

What is the MOA of the azoles?

A

binds to the enzyme responsible for converting lanosterol to ergosterol, making the cell membrane leaky

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30
Q

What are the three major mechanisms by which resistance to azole are brought about?

A
  • efflux pumps
  • Mutations in enzymes
  • Decreased ergosterol content in the membrane
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31
Q

What are the major side effects of ketoconazole?

A

High degree of p450 inhibition

Systemic toxicity

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32
Q

Which azole has the highest therapeutic index?

A

Fluconazole

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33
Q

What are the two major benefits of fluconazole over other azoles?

A

Lowest p450 interaction

can penetrate CNS

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34
Q

What is the agent of choice in treating candidiasis?

A

fluconazole

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35
Q

What is the agent of choice in treating cryptococcosis?

A

fluconazole

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36
Q

What is the agent of choice for treating coccidiomycosis?

A

Fluconazole

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37
Q

True or false: fluconazole is poorly water soluble

A

False

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38
Q

True or false: itraconazole is poorly water soluble

A

True

39
Q

What is the drug that will reduce the effectiveness of itraconazole? Why?

A

PPIs or other antacids, since itraconazole needs a low pH for absorption

40
Q

What is the major deterrent for absorption of itraconazole?

A

high pH

41
Q

Does itraconazole penetrate the CNS?

A

No

42
Q

What is itraconazole used to treat?

A

Blasto
Coccidio
Histo
Sporo

43
Q

What are the major drug interactions of itraconazole? (3)

A
  • Reduce Rifampin levels
  • Raises digoxin levels
  • May affect coumadin and hypoglycemic drug levels
44
Q

What is the treatment of choice for aspergillosis?

A

Voriconazole

45
Q

What are the adverse effects of Voriconazole?

A

transient visual disturbances

Inhibit p450s

46
Q

True or false: Voriconazole is water soluble and is readily absorbed from the GI tract

A

True

47
Q

Which azole has the broadest spectrum of activity?

A

Posaconazole

48
Q

What is the major issue with Posaconazole?

A

Strong inhibitor of p450s

49
Q

What is posaconazole used to treat? (2)

A

Aspergillus, and mucormycosis

50
Q

What is the MOA of 5FC?

A

Converted into 5FU in the cell, and disrupts DNA synthesis

51
Q

What is the transporter in fungi that brings 5FC into the cell?

A

Cytosine permease

52
Q

What is 5FC used to treat (1)? Is this effective enough to be given alone?

A

Cryptococcal infection

Part of a combination treatment

53
Q

What is the major adverse effect of 5FC?

A

myelosuppression

54
Q

How is 5FC administered? is it water soluble?

A

Well absorbed from GI tract (PO)

Water soluble

55
Q

What is the MOA of echinocandins?

A

inhibit the synthesis of beta-glucans

56
Q

Why are the echinocandins less toxic than the azoles or amp B?

A

We do not have glucans

57
Q

What happens when echinocandins block beta-glucan synthesis?

A

Weakened fungal cell wall

58
Q

What are echinocandins usually used to treat?

A

Candida or aspergillus infections

59
Q

How are echinocandins administered? Do they penetrate the CNS?

A

IV

Poor penetration of the CNS

60
Q

What are the two antifungals that are administered systemically for a topical infection?

A

Griseofulvin

Allylamines

61
Q

How is Griseofulvin administered? Why?

A

Microcrystalline form with a fatty meal, since it is very water insoluble

62
Q

Where does Griseofulvin tend to concentrate in the body? Why is this good?

A

Keratin precursor cells, which means it provide prolonged resistance to fungal invasion

63
Q

What is the MOA of Griseofulvin ?

A

Unclear, maybe microtubule function

64
Q

What are the drug interactions with Griseofulvin?

A

Increases warfarin metabolism

Decreases oral contraceptives

65
Q

What are the side effects with Griseofulvin?

A

HA
Hepatotoxic
GI distress

66
Q

What is Griseofulvin usually used to treat?

A

Dermatophyte infections

67
Q

What is the MOA of allylamines?

A

Inhibit the squalene epoxidase

68
Q

What is the first line treatment for onychomycosis? What type of antifungal is this?

A

terbinafine–allylamine

69
Q

What are the route of administration for terbinafine?

A

oral or topically

70
Q

What is terbinafine used to treat?

A

onychomycosis

71
Q

If terbinafine is given systemically, where does it concentrate?

A

Keratinized tissue

72
Q

What is the major adverse effect with terbinafine?

A

Hepatitis

73
Q

Does terbinafine interact with the p450 system?

A

No

74
Q

Which of the azoles are used topically?

A

Clotrimazole

Miconazole

75
Q

Which of the allylamines are used topically?

A

terbinafine

Naftifine

76
Q

Which of the polyenes are used topically?

A

Nystatin

77
Q

What is the MOA of nystatin?

A

binds to ergosterol (just like amp B)

78
Q

Why is nystatin only used topically?

A

Poor absorption

Very toxic

79
Q

What is nystatin usually used to treat?

A

Thrush or candida vaginitis

80
Q

What is the alternative to Nystatin for oral thrush?

A

Topical Clotrimazole or Miconazole

81
Q

Septate hyphae that branch at 45 degrees =?

A

Aspergillus

82
Q

What is the treatment of choice for: Aspergillosis?

A

Voriconazole

83
Q

What is the treatment of choice for: Blastomycosis? (2)

A

Itraconazole

AMP B if bad

84
Q

What is the treatment of choice for: vaginal candidiasis

A

Clotrimazole or micoazole

85
Q

What is the treatment of choice for: thrush?

A

Nystatin

Topical azole

86
Q

What is the treatment of choice for: Esophageal candidiasis?

A

Fluconazole

87
Q

What is the treatment of choice for: invasive candidiasis?

A

Fluconazole

88
Q

What is the treatment of choice for: cryptococcosis?

A

Amp B + fluconazole

89
Q

What is the treatment of choice for: Histoplasmosis?

A

Amp B + itraconazole

90
Q

What is the treatment of choice for: Mucormycosis

A

Amp B

91
Q

What is the treatment of choice for: Sporotrichosis

A

Itraconazole

92
Q

What is the treatment of choice for: Dermatomycosis

A

Terbinafine

93
Q

What is the treatment of choice for: Onychomycosis

A

Terbinafine or itraconazole