Pharm antifungal Flashcards

1
Q

what are the major categories of pathogenic fungi?

A

yeast: candida, cryptococcus
mold: aspergillus, fusarium, mucorales
endmic mycoses: histoplasma, coccidioides, blastomyces, pneumocystis jiroveci

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2
Q

what are the categories of antifungal agents?

A

triazoles, polyenes, echinocandins, flucytosine

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3
Q

what are the triazole antifungals?

A

fluconazole, itraconazole, posaconazole, voriconazole

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4
Q

triazoles MOA

A

impede ergosterol synthesis through direct inhibition of the cytochrome P450 dependent enzyme 14-alpha-sterol demethylase (necessary for biosynthetic pathway or ergosterol)
FUNGALSTATIC

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5
Q

triazole adverse effects

A

relatively safe - liver enzyme abnormalities, GI side effects, voriconazole = visual disturbances

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6
Q

what is a specific side effect to voriconazole

A

visual disturbance (Visual Voriconazole)

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7
Q

triazole drug interactions? which has lowest?

A

potential inhibitors of CYP450 - fluconazole has lowest

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8
Q

what is fluconazole the treatment of choice for?

A

susceptible candidiasis; severe thrush/esophageal candidiasis; secondary treatment and prophylaxis of cryptococcal meningitis

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9
Q

what is itrazonazole the treatment of choice for?

A

secondary treatment and prophylaxis of systemic histoplasmosis

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10
Q

what is voriconazole the treatment of choice for?

A

invasive aspergillosis

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11
Q

what is posaconazole the treatment of choice for?

A

Prophylaxis of aspergillosis/immunocompromised patients

P = Prophylaxis Posaconazole

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12
Q

amphotericin B MOA

A

inhibition of ergosterol - generates pores

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13
Q

amphotericin B class

A

polyene macrolide

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14
Q

what are the polyene macrolides?

A

amphotericin B and nystatin

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15
Q

amphotericin B clinical use

A

life-threatening invasive fungal infections - broad spectrum

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16
Q

what is amphotericin used with in immunocompromised hosts?

A

flucytosine

17
Q

amphotericin B side effects

A

poor tolerability - nephrotoxicity (so common expected); acute infusion related reactions (fever, chills, rigors); electrolyte abnormalities (d/t pores in cell and kidney dysfunction) - hypomagnesemia, hypokalemia

18
Q

what has been done to amphotericin B to give it better tolerability?

A

lipid formulations - more renal protective and less infusion-related side effects

19
Q

what are the echinocandins?

A

-fungins

caspofungin, micafungin, anidulafungin

20
Q

disadvantages to echinocandins

A

expensive and only available IV

21
Q

echinocandins (-fungins) mechanism

A

cell wall synthesis inhibitor - inhibit synthesis of beta (1,3)-D-glucan

22
Q

echinocandins (-fungins) clinical uses

A

life-threatening fungal infections unresponsive to older agnets

23
Q

echinocandins (-fungins) side effects

A

low side effect profile (some liver toxicity possible)

24
Q

flucytosine MOA

A

pyrimidine analogue that inhibits DNA and RNA synthesis - only oral

25
Q

flucytosine clinical use

A

ALWAYS used in combination with something else (amphotericin B usually) - only active against cryptococcus and some candida

26
Q

flucytosine side effects

A

chemotherapy like - bone marrow toxicity (decreased WBC and anemia), liver disfunction possible, GI intolerances

27
Q

what are the allylamines?

A

tolnaftate and terbinafine

28
Q

tolnaftate and terbinafine (allylamines) MOA

A

inhibit ergosterol synthesis by inhibiting squalene epoxidase = increase levels of squalene which are toxic to fungi

29
Q

what are the clinical uses of tolnaftate and terbinafine (allylamines)?

A

TOPICAL dermatophytes

30
Q

tolnaftate and terbinafine (allylamines) side effects

A

hepatotoxicity - otherwise low side effect profile

31
Q

what is terbinafine also effective against?

A

onychomycoses