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Pharmacology 2 > Antifungals > Flashcards

Antifungals Flashcards

1
Q

what makes it challenging to target and destroy fungus?

A

they are eukaryotic organisms

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2
Q

which 2 mycoses make up the majority of systemic fungal infections?

A

aspergillus
candida

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3
Q

what are the 2 most common sites of fungal infection?

A

lungs
CNS

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4
Q

what 4 conditions/uses cause an increased risk of fungal infection?

A

broad spectrum antibiotics
chemotherapy
immunosuppressive therapy
chronic corticosteroids

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5
Q

what 2 disease states increase the risk of fungal infection?

A

AIDS/HIV
diabetes mellitus

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6
Q

why is there an increase in side effects of anti-fungal drugs?

A

they have homologous metabolic pathways for protein synthesis and cell division as humans

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7
Q

_____ is the sterol in human cells, while ____ is a unique sterol to the fungal cell membrane. Both are structurally similar.

A

cholesterol
ergosterol

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8
Q

why are antibiotics ineffective in fungal infections?

A

fungi have cell walls made of B-glucans and chitin, which are more rigid that bacterial cell walls

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9
Q

how does resistance occur in ergosterol binding drugs?

A

low concentrations of ergosterol

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10
Q

polyene that is an ergosterol binding drug; lipophilic part binds to ergosterol and hydrophilic part allows formation of pores, losing electrolytes and leads to cell death

A

amphotericin B

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11
Q

broadest spectrum against most pathogenic fungi

A

amphotericin B

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12
Q

using amphotericin B with which drug increases it’s uptake?

A

flucytosine

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13
Q

what are the 2 uses of amphotericin B?

A

initial (induction) therapy for invasive fungal infections
cryptococcal meningitis in HIV patients

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14
Q

how must amphotericin be given and why?

A

infusion
large molecule

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15
Q

what are the 4 infusion ADR of amphotericin B?

A

“Amphotericin makes you feel ampho-terrible with fever, chills, muscle spasms, and hypotension”

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16
Q

what should be done before starting amphotericin B? what can be given to minimize effects? (3)

A

1mg test dose to assess risk

antihistamine
antipyretics
corticosteroids

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17
Q

what is a dose-limiting ADR of amphotericin B? what should be total daily dose be?

A

nephrotoxicity
1.5 mg/kg

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18
Q

what dose is nephrotoxicity d/t amphotericin B no longer reversible?

A

3.6-4 gm

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19
Q

what kind of formulations of amphotericin B may cause less S/E d/t a decrease in binding to cholesterol in the renal cell membrane?

A

lipid-based formulations

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20
Q

which amphotericin B formulation has mild infusion-related S/E?

A

liposomal amphotericin B (L-AmB)

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21
Q

which 2 amphotericin B formulation have moderate infusion-related S/E?

A

ABLC (lipid complex)
ABCD (colloidal dispersion)

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22
Q

which amphotericin B formulation has high infusion-related S/E?

A

AmB-d deoxycholate (salt form)

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23
Q

what can nephrotoxicity d/t amphotericin lead to in a patient?

A

anemia (decreased production of erythropoietin)

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24
Q

for the treatment of cryptococcal meningitis in HIV patients, what can be added to amphotericin B? (2)

A

flucytosine
fluconazole

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25
Q

topical polyene antifungal that is much more systemically toxic than amphotericin B?

A

nystatin

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26
Q

2 uses for nystatin?

A

superficial infections of candida albicans
oral candidiasis (2nd line)

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27
Q

2 administration routes of nystatin for oral candidiasis?

A

suspension; swish and hold
troches (throat lozenge)

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28
Q

DNA synthesis inhibitor

A

flucytosine

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29
Q

what is flucytosine converted to in fungal cells and how?

A

5-FU
cytosine permease
deaminase

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30
Q

how does resistance occur in flucytosine?

A

defect in enzyme that converts 5-FC to 5-FU

31
Q

administration of flucytosine (5-FC)?

A

oral

32
Q

5 ADR of flucytosine?

A

“Naughty Vampires (flucytosine) Demand Hearty Blood Meals”

Nausea
Vomiting
Diarrhea
Hepatotoxicity
Bone Marrow suppression (dose-dependent)

33
Q

what med is used with amphotericin B for synergistic effect?

A

flucytosine

34
Q

-azoles

A

ergosterol synthesis inhibitors

35
Q

how does resistance occur in azoles?

A

altered binding d/t mutation in gene coding for fungal P450 enzyme

36
Q

name the 3 ergosterol synthesis inhibitor imidazoles?

A

“Mic went on Keto to cloTrim down”

ketoconazole
clotrimazole
miconazole

37
Q

name the 5 ergosterol synthesis inhibitor triazoles?

A

“I want to Tri to be a FI VIP”

fluconazole
itraconazole
voriconazole
isavuconazole
posaconazole

38
Q

why are triazoles better than imidazoles?

A

have better selective inhibition of fungal P450 enzyme

39
Q

which azole has the highest risk for D-D interaction?

A

ketoconazole

40
Q

which 2 drugs have the least risk for D-D interaction d/t having the least inhibition of CYP3A4?

A

fluconazole
posaconazole

41
Q

2 ADR of ketoconazole?

A

“Keto is for girls - gynecomastia and mestrual irregularities”

42
Q

use of imidazoles?

A

cutaneous mycoses (fungus)

43
Q

use of triazoles?

A

systemic mycoses (fungus)

44
Q

spectrum of fluconazole?
elimination?
CYP inhibition?
2 ADR?

A

C. albicans
renal
CYP2C9

alopecia
hepatotoxicity

45
Q

spectrum of itraconazole?
elimination?
CYP inhibition?
3 ADR?

A

C. albicans
aspergilli
liver
CYP3A4

diarrhea
CHF
hepatotoxicity

46
Q

which environment is needed for itraconazole to be absorbed?

A

low pH (acidic)

47
Q

spectrum of voriconazole?
elimination?
CYP inhibition? (2)
3 ADR?

A

broad
liver
CYP3A4. CYP2C19

rash
visual disturbance
hepatotoxicity

48
Q

spectrum of posaconazole?
elimination?
CYP inhibition?
ADR?

A

broad
fecal
CYP3A4

less hepatotoxicity

49
Q

what spectrum of activity should we aim to use?

A

narrow spectrum

50
Q

spectrum of isavuconazole?
elimination?
CYP inhibition?
ADR?

A

C. albicans
aspergilli
cryptococcus
liver
CYP3A4

less D-D and ADR

51
Q

what is the 1st line treatment for oral candidiasis? (3)

A

clotrimazole troche
miconazole
+/- nystatin (last option)

52
Q

treatment for resistant oral candidiasis?

A

oral fluconazole

53
Q

-funin / -fungerp

A

echinocandins; fungal cell wall inhibitors

54
Q

inhibit B-glucans and are highly selective since humans don’t have it

A

echinocandins; fungal cell wall inhibitors (-fungin)

55
Q

2 uses for echinocandins; fungal cell wall inhibitors?

A

most candida
azole- and polyene-resistant species

56
Q

how does resistance occur in echinocandins; fungal cell wall inhibitors?

A

altered B-glycan synthase (too much efflux pump)

57
Q

6 ADR of echinocandins; fungal cell wall inhibitors?

A

“F HERE”

Fever
Headache
Erythema
Rash
Embryotoxic

58
Q

why do echinocandins have a low bioavailability? route of administration?

A

large molecule
IV only

59
Q

drugs that induce which enzyme will lead to a need of increased caspofungin dose?

A

P450 enzyme

60
Q

what 2 immunosuppressants are increased when used with caspofungin?

A

tacrolimus
cyclosporin

61
Q

the only echinocandin used orally and approved for vulvovaginal candidiasis?

A

ibrexafungerp

62
Q

what 2 immunosuppressant should be avoided when taking caspofungin?

A

tacrolimus
cyclosporin

63
Q

what are the 2 uses for clotrimazole and miconazole?

A

vaginal candidas
oral candidas

64
Q

topical miconazole inhibits metabolism of which drug?

A

warfarin

65
Q

-fine

A

allyamines

66
Q

accumulate in keratinized layer of skin and nails; inhibit fungal enzyme which usually creates lanosterol of fungus, leading to depletion of ergosterol (inhibiting first stop of ergosterol synthesis)

A

allyamines (-fine)

67
Q

2 uses for allyamines?

A

onychomycosis of toenails/fingernails
athlete’s foot (tinea pedis)

68
Q

2 ADRs of terbinafine?

A

GI
CYP2D6 inhibitor

69
Q

accumulates in keratinized layer of skin, hair, and nails; inhibits fungal cell mitosis

A

griseofulvin

70
Q

accumulates in keratinized layer of skin, hair, and nails; inhibits first step of ergosterol synthesis like terbinafine

A

tolnaftate

71
Q

uses for griseofulvin and tolnaftate?

A

dermatophytes/tinea
superficial fungal infections of skin, scalp, and hair

72
Q

6 ADRs of griseofulvin?

A

GI upset
dizziness
confusion
hepatotoxicity
leukopenia
photosensitivity

73
Q

how should griseofulvin be taken to increase absorption?

A

with fatty food

74
Q

what can be used as an adjunct therapy for tinea capitis?

A

ketoconazole shampoo

Pharmacology 2 (22 decks)

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