Pharm - Antifungals Flashcards

1
Q

Aspergillus is a

A

mold

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2
Q

Candida spp. and cryptococcus are

A

yeasts

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3
Q

Histoplasma, trychophyton, and blastomyces are

A

other fungi

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4
Q

Name some benefits of fungi

A

Source for many meds (statins, beta-lactam abx)
Food (edible mushrooms)
Insect control
Biotechnology
Decomposers

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5
Q

Invasive aspergillosis

A

Hyphae invade lung vasculature, resulting in thrombosis and infarction

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6
Q

Esophageal candidiasis

A

Spectrum from scattered plaque like lesions in mild disease to very shaggy esophagus in severe cases
Can cause invasive tissue infections, spread to tissues, blood (candidemia), and GU tract

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7
Q

Cryptococcosis

A

CNS involvement

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8
Q

Blastomycosis

A

Deep seated fungal infection

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9
Q

Histoplasmosis

A

Fungal infection of the lungs, often from inhalation of bird droppings

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10
Q

Onychomycosis caused by what fungus

A

Trychophyton rubrum

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11
Q

Murcormycosis, aka

A

Zygomycosis

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12
Q

Dermatophytoses, AKA

A

Tinea infection

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13
Q

How recognize a fungal infection

A

Symptoms (inflammatory response, fever)
Risk factors
Radiography
Serological testing
Tissue/blood culture

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14
Q

Galactomannan assay for

A

aspergillus

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15
Q

B-glucan used for

A

Candida

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16
Q

Why are fungal infections “challenging”?

A

Hard to diagnose
Potential for drug toxicity
Resistance
Aggressiveness of pathogens

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17
Q

Largest class of antifungals is

A

azoles

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18
Q

Name the classes of antifungals discussed

A

Azoles
Polyenes
Flucytosine
Echinocandins
Terbinafine
Tavaborale
Ibrexafungerp (new)

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19
Q

3 targets for antifungal meds

A

Cell membrane (ampho, nystatin, azoles, Terbinafine)
DNA synthesis (flucytosine)
Cell wall (echinocandins, ibxrexafungerp)

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20
Q

Fungistatic

A

Chemicals that inhibit fungal growth

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21
Q

Fungicidal

A

Capable of destroying fungi

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22
Q

Amphotericin B class

A

Polyene Macrolide antifungal

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23
Q

Ampho only available in what form

A

IV

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24
Q

Ampho long or short half life?

A

Long (15 days)

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25
Q

Ampho dose adjust for renal or hepatic function?

A

No

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26
Q

Amphotericin MOA

A

Binds to and disrupts ergosterol in fungal cell membrane

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27
Q

Amphotericin coverage

A

Broad, including yeasts, cryptococcus, histoplasma, blastomyces, aspergillus

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28
Q

Adverse effects of Amphotericin

A

“Amphoterrible”
Infusion related symptoms: fever, chills, rigors, hypotension

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29
Q

How to reduce adverse effects of ampho?

A

Prophylaxis with acetaminophen, Benadryl, hydrocortisone

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30
Q

________ used to treat rigors associated with Ampho

A

Meperidine

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31
Q

Adverse effects of chronic Ampho use

A

Renal toxicity
Hepatic toxicity

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32
Q

Describe the purpose of “lipid” ampho?

A

Created to improve tolerability

Abelcet
Amphotec
Ambisome (liposomal amphotericin)

Reduces toxicity by being packaged with hydrophilic portions

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33
Q

Clinical use of ampho

A

For “life-saving” use of nasty fungal infections

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34
Q

Ambisone is considered 1st line ALTERNATIVE option for

A

invasive aspergillus

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35
Q

Flucytosine only available in what form

A

Oral pills

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36
Q

Flucytosine large or small Vd

A

Large (enter CNS)

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37
Q

Flucytosine MOA

A

Taken up by fungal cells, converted to 5-FU and then 5-FdUMP and 5-FdUTP (inhibiting fungal DNA and RNA synthesis)

38
Q

Flucytosine has synergistic action with ampho, so it is often used in combo to treat

A

Cryptococcus and Candida meningitis

39
Q

Adverse effect of Flucytosine?

A

Myelosuppression (Anemia, thrombocytopenia, leukopenia)

Potentially hepatotoxic

40
Q

Flucytosine mostly used clinically to treat

A

Cryptococcal meningitis

41
Q

Flucytosine mono or polytherapy?

A

Usually polytherapy

42
Q

Imidazoles have a 5 membered ring with a __________ in the X position

A

C

43
Q

Triazoles have a 5 membered ring with a ______________ in the X position

A

N

44
Q

Name the imidazoles

A

Ketoconazole
Miconazole
Clotrimazole

45
Q

Name the triazoles

A

Fluconazole
Itraconazle
Voriconazole
Posaconazole
Isavuconazole

46
Q

Azoles MOA

A

Inhibit fungal sterol (ergosterol) synthesis by inhibiting the cytochrome P-450 enzyme that converts Lanosterol to ergesterol (Cell Membrane)

47
Q

Azoles - fungistatic or fungicidal?

A

Fungistatic

48
Q

Adverse effects of azoles

A

GI upset
LFTs?

49
Q

Which azole is known to worsen heart failure?

A

Itraconazole

50
Q

Azole drug interaction

A

CYP 450 inhibitors (usually 3A4)

51
Q

Ketoconazole used for

A

Seborrheic derm, athlete’s foot, ringworm

52
Q

“Unexpected” use for Ketoconazole

A

Oral tablets for prostate cancer

53
Q

How is oral itraconazole best absorbed?

A

With Coca Cola beverage

54
Q

Itraconazole coverage

A

Candida, Aspergillus and others

55
Q

Itraconazole used in the management of

A

Onychomycosis (amongst other things)

56
Q

Fluconazole usually tolerated ________ and has a ________ Vd

A

Well, high

57
Q

Primary clinical use of Fluconazole

A

Tx and prophylaxis of coccidiodal and cryptococcal meningitis

Also first line for mild cases of candidemia

58
Q

Fluconazole has no activity against

A

Aspergillus

59
Q

Fluconazole has resistance seen in

A

C. kruse, C. glabrata and others

60
Q

Voriconazole has excellent oral

A

bioavailability

61
Q

Voriconazole adverse effects

A

Hepatic toxicity, rash, and visual changes

62
Q

Voriconazole coverage

A

Broad

Candida (including invasive)
Aspergillus (1st line for invasive)

63
Q

Posaconazole coverage

A

Candida
Aspergillus
Other molds

64
Q

___________ is approved for prophylaxis of fungal infections in immunosuppressed patients

A

Posaconazole

65
Q

________ considered 1st line for esophageal candidiasis

A

Posaconazole

66
Q

Isavuconazole is a ___________

A

pro drug

67
Q

Isavuconazole is 1st line alternative for invasive

A

Aspergillus

68
Q

IV form of Isavuconazole requires administration through a

A

inline filter (to remove particles)

69
Q

Topical azole antifungals useful for

A

Vulvovaginal yeast infection
Athlete’s foot
Diaper rash

70
Q

Efinaconazole

A

Topical azole antifungal used for Onychomycosis

71
Q

Efinaconazole is applied once daily for ___________ weeks

A

48

72
Q

Tavaborole

A

Topical solution approved for Onychomycosis

73
Q

Echinocandins active against

A

Candida and Aspergillus

74
Q

Echinocandins only in what form

A

IV

75
Q

Echinocandins MOA

A

Disrupts cell integrity and leads to cell death

76
Q

Echinocandins are _______ against Candida

A

Fungicidal

77
Q

Echinocandins are _________ against Aspergillus

A

Fungistatic

78
Q

Adverse effects of Echinocandins

A

GI effects
Flushing reactions

79
Q

Echinocandins potential for drug interactions

A

Much less than azoles

Caspofungin
Micafungin
Anidulafungin

80
Q

Main use for Echinocandins

A

1st option for moderately to severely ill patients with invasive candidiasis

81
Q

Ibrexafungerp

A

Considered fungicidal against Candida

82
Q

Terbinafine

A

Both cream and pill form
1st option for Onychomycosis

Monitor LFT’s

83
Q

Terbinafine MOA

A

Interferes with ergosterol synthesis via the inhibition of the fungal enzymes squalene epoxidase

84
Q

Tolnaftate

A

Creams, powders, and sprays

Used for treatment of athlete’s foot and other superficial fungal infections

No activity against Candida

85
Q

Nystatin

A

Polyene antifungal
Active against Candida
Can be cream, powder, or oral rinse

86
Q

Factors to include when choosing antifungal treatment

A

Organism
Site of infection
Severity of infection
Response to previous therapy

87
Q

Guidelines for fungal treatments

A

IDSA

88
Q

Need to consider pt _________ function before prescribing antifungals

A

Organ (liver/kidney)

89
Q

Azoles and Ibrexafungerp are category ____________ on the pregnancy status chart

A

C or D

90
Q

What drug can actually shorten QTc?

A

Isavuconazole