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diseases that are infectious > Antifungal Pharmacology > Flashcards

Antifungal Pharmacology Flashcards

1
Q

what is the primary difference between fungal and mammalian cells

A

the cell wall and use of ergosterol (instead of cholesterol) to stabilize their cytoplasmic membrane

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2
Q

what is the mechanism of action of allylamines

A

squalene epoxidase inhibitors that block ergosterol synthesis and cause the buildup of squalene in
the cell which is toxic in fungi

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3
Q

what is terbinafine and its indication

A

brand: Lamisil
class: Allylamine antifungal
indication: tinea infections

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4
Q

what is the black box warning for terbinafine

A

severe hepatitis

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5
Q

how do polyene antifungals work

A

-have a high affinity for sterol containing membranes
-insert themselves into plasma membrane causing the cells to leak (fungicidal)

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6
Q

are polyenes broad spectrum or narrow spectrum

A

broad spectrum

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7
Q

polyenes have a higher affinity for what membranes which accounts for greater toxicity to fungal cells

A

membranes containing ergosterol over cholesterol

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8
Q

what are the 4 available formulations for Amphotericin B

A

-conventional
-colloidal dispersion
-liposomal
-lipid complex

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9
Q

what antifungal is reserved for life-threatening infections

A

amphotericin B

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10
Q

what is the major concern for amphotericin B and how it manifests

A

nephrotoxicity manifests as excess urine potassium (kaliuresis) and reduced blood potassium (hypokalemia)

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11
Q

what is the conventional amphotericin B formulation

A

non-lipid complex with deoxycholate for IV infusion

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12
Q

what is the amphotericin B colloidal dispersion (ABCD) formulation

A

lipid complex of amphotericin B and cholesterol sulfate that concentrates in the blood and reduces risk of nephrotoxicity

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13
Q

what is the liposomal amphotericin B (LAMB) formulation

A

bilayer liposome with amphotericin B intercalated within membrane and is less nephrotoxic and causes least severe infusion-related reaction

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14
Q

what is the amphotericin B lipid complex formulation

A

amphotericin B complexed with two phospholipids that concentrates in tissues

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15
Q

what class is amphotericin B (AMB) and natamycin

A

polyene antifungal

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16
Q

what is natamycin used to treat

A

fungal keratitis (eye infection)

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17
Q

what is the mechanism of action of azole antifungals

A

block C-14a demethylase resulting in accumulation of ergosterol precursors that results in leaky membranes and leads to cell death

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18
Q

what liver CYP enzymes do azole antifungals impair

A

CYP3A4

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19
Q

what are the systemic azole antifungals

A

fluconazole
ketoconazole
itraconazole
voriconazole
posaconazole
isavuconazole

20
Q

what fungus is often resistant to fluconazole

A

Candida Krusei

21
Q

which azole has the best CSF penetration making it the preferred for fungal meningitis

A

fluconazole

22
Q

which azole has the best oral bioavailability and absorption is not dependent on stomach pH

A

fluconazole

23
Q

Fluconazole brand and uses

A

Brand: diflucan
uses: candidiasis and cryptococcal meningitis

24
Q

what azole has pH dependent absorption where gastric acids improve the absorption and needs to be administered with acidic drinks

A

ketoconazole

25
Q

what causes decreased absorption of ketoconazole in HIV patients

A

achlorhydria (absent/low stomach acid)

26
Q

ADR and black box warning for ketoconazole

A

many drug interactions
BBW for hepatotoxicity

27
Q

Itraconazole brand and uses

A

brand: Sporanox
uses: blastomycosis, candidiasis, histoplasmosis

28
Q

what azole has pH dependent absorption and is recommended to take the capsule with food and acidic drinks and the oral solution on an empty stomach

A

itraconazole

29
Q

does the oral solution or capsule of itraconazole have superior bioavailability

A

oral solution

30
Q

major contraindication for use of itraconazole

A

should not be used in patients with congestive heart failure (cardiotoxicity)

31
Q

voriconazole brand and uses

A

brand: vfend
uses: aspergillosis, candidiasis (including C. krusei)

32
Q

what is voriconazole formulated with that may require renal adjustment in patients

A

cyclodextrin

33
Q

ADR of voriconazole

A

visual disturbance

34
Q

posaconazole brand and uses

A

brand: noxafil
uses: aspergillosis and candidiasis

35
Q

which azole is a synthetic analog of itraconazole but more active against yeasts and molds

A

posaconazole

36
Q

isavuconazole formulation, brand and uses

A

formulated as isavuconazonium sulfate (Cresemba) that does not have a cyclodextrin vehicle
uses: aspergillosis and mucormycosis

37
Q

what is flucytosine and its mechanism

A

oral prodrug that is selectively converted in fungi to 5-flurouridine monophosphate which inhibits nucleic acid synthesis

38
Q

why is flucytosine never used alone (always in combo with AMB)

A

due to rapid development of resistance

39
Q

uses for flucytosine

A

candidiasis and cryptococcosis
-high CSF concentration for treating fungal meningitis

40
Q

ADR and drug interactions of flucytosine

A

ADR: marrow suppression leading to leukopenia
drug interactions: avoid drugs that can also cause marrow suppression

41
Q

what is the use for Griseofulvin antifungal

A

tinea infections only

42
Q

what are 3 echinocandins and the brands

A

Caspofungin (cancidas)
micafungin (mycamine)
anidulafungin (eraxis)

43
Q

coverage of echinocandins

A

candida including fluconazole resistant c.krusei and c.glabrata

44
Q

mechanism of action of echinocandins

A

lipopeptide that inhibit fungal cell wall synthesis and only given IV infusion

45
Q

3 advantages of echinocandins

A

-less CYP interactions compared to azoles
-low toxicity
-no renal dose adjustment

46
Q

2 disadvantages to echinocandins

A

-do not obtain therapeutic concentrations in eyes, CNS, and urine
-adjust for hepatic disease

diseases that are infectious (7 decks)

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