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Pharmacology 2 > Antifungals > Flashcards

Antifungals Flashcards

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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
topical polyene antifungal that is much more systemically toxic than amphotericin B?
nystatin
26
2 uses for nystatin?
superficial infections of candida albicans oral candidiasis (2nd line)
27
2 administration routes of nystatin for oral candidiasis?
suspension; swish and hold troches (throat lozenge)
28
DNA synthesis inhibitor
flucytosine
29
what is flucytosine converted to in fungal cells and how?
5-FU cytosine permease deaminase
30
how does resistance occur in flucytosine?
defect in enzyme that converts 5-FC to 5-FU
31
administration of flucytosine (5-FC)?
oral
32
5 ADR of flucytosine?
"Naughty Vampires (flucytosine) Demand Hearty Blood Meals" **Nausea Vomiting Diarrhea Hepatotoxicity Bone Marrow suppression (dose-dependent)**
33
what med is used with amphotericin B for synergistic effect?
flucytosine
34
-azoles
ergosterol synthesis inhibitors
35
how does resistance occur in azoles?
altered binding d/t mutation in gene coding for fungal P450 enzyme
36
name the 3 ergosterol synthesis inhibitor imidazoles?
"Mic went on Keto to cloTrim down" **ketoconazole clotrimazole miconazole**
37
name the 5 ergosterol synthesis inhibitor triazoles?
"I want to Tri to be a FI VIP" **fluconazole itraconazole voriconazole isavuconazole posaconazole**
38
why are triazoles better than imidazoles?
have better selective inhibition of fungal P450 enzyme
39
which azole has the highest risk for D-D interaction?
ketoconazole
40
which 2 drugs have the least risk for D-D interaction d/t having the least inhibition of CYP3A4?
fluconazole posaconazole
41
2 ADR of ketoconazole?
"Keto is for girls - **gynecomastia and mestrual irregularities"**
42
use of imidazoles?
cutaneous mycoses (fungus)
43
use of triazoles?
systemic mycoses (fungus)
44
spectrum of fluconazole? elimination? CYP inhibition? 2 ADR?
C. albicans renal CYP2C9 alopecia hepatotoxicity
45
spectrum of itraconazole? elimination? CYP inhibition? 3 ADR?
C. albicans aspergilli liver CYP3A4 diarrhea CHF hepatotoxicity
46
which environment is needed for itraconazole to be absorbed?
low pH (acidic)
47
spectrum of voriconazole? elimination? CYP inhibition? (2) 3 ADR?
broad liver CYP3A4. CYP2C19 rash visual disturbance hepatotoxicity
48
spectrum of posaconazole? elimination? CYP inhibition? ADR?
broad fecal CYP3A4 less hepatotoxicity
49
what spectrum of activity should we aim to use?
narrow spectrum
50
spectrum of isavuconazole? elimination? CYP inhibition? ADR?
C. albicans aspergilli cryptococcus liver CYP3A4 less D-D and ADR
51
what is the 1st line treatment for oral candidiasis? (3)
clotrimazole troche miconazole +/- nystatin (last option)
52
treatment for resistant oral candidiasis?
oral fluconazole
53
-funin / -fungerp
echinocandins; fungal cell wall inhibitors
54
inhibit B-glucans and are highly selective since humans don't have it
echinocandins; fungal cell wall inhibitors (-fungin)
55
2 uses for echinocandins; fungal cell wall inhibitors?
most candida azole- and polyene-resistant species
56
how does resistance occur in echinocandins; fungal cell wall inhibitors?
altered B-glycan synthase (too much efflux pump)
57
6 ADR of echinocandins; fungal cell wall inhibitors?
"F HERE" **Fever Headache Erythema Rash Embryotoxic**
58
why do echinocandins have a low bioavailability? route of administration?
large molecule IV only
59
drugs that induce which enzyme will lead to a need of increased caspofungin dose?
P450 enzyme
60
what 2 immunosuppressants are increased when used with caspofungin?
tacrolimus cyclosporin
61
the only echinocandin used orally and approved for vulvovaginal candidiasis?
ibrexafungerp
62
what 2 immunosuppressant should be avoided when taking caspofungin?
tacrolimus cyclosporin
63
what are the 2 uses for clotrimazole and miconazole?
vaginal candidas oral candidas
64
topical miconazole inhibits metabolism of which drug?
warfarin
65
-fine
allyamines
66
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)
allyamines (-fine)
67
2 uses for allyamines?
onychomycosis of toenails/fingernails athlete's foot (tinea pedis)
68
2 ADRs of terbinafine?
GI CYP2D6 inhibitor
69
accumulates in keratinized layer of skin, hair, and nails; inhibits fungal cell mitosis
griseofulvin
70
accumulates in keratinized layer of skin, hair, and nails; inhibits first step of ergosterol synthesis like terbinafine
tolnaftate
71
uses for griseofulvin and tolnaftate?
dermatophytes/tinea superficial fungal infections of skin, scalp, and hair
72
6 ADRs of griseofulvin?
GI upset dizziness confusion hepatotoxicity leukopenia photosensitivity
73
how should griseofulvin be taken to increase absorption?
with fatty food
74
what can be used as an adjunct therapy for tinea capitis?
ketoconazole shampoo

Pharmacology 2 (22 decks)

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