Antifungal Pharmacology

Question 1

what is the primary difference between fungal and mammalian cells

Answer 1

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

Question 2

what is the mechanism of action of allylamines

Answer 2

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

Question 3

what is terbinafine and its indication

Answer 3

brand: Lamisil
class: Allylamine antifungal
indication: tinea infections

Question 4

what is the black box warning for terbinafine

Answer 4

severe hepatitis

Question 5

how do polyene antifungals work

Answer 5

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

Question 6

are polyenes broad spectrum or narrow spectrum

Answer 6

broad spectrum

Question 7

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

Answer 7

membranes containing ergosterol over cholesterol

Question 8

what are the 4 available formulations for Amphotericin B

Answer 8

-conventional
-colloidal dispersion
-liposomal
-lipid complex

Question 9

what antifungal is reserved for life-threatening infections

Answer 9

amphotericin B

Question 10

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

Answer 10

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

Question 11

what is the conventional amphotericin B formulation

Answer 11

non-lipid complex with deoxycholate for IV infusion

Question 12

what is the amphotericin B colloidal dispersion (ABCD) formulation

Answer 12

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

Question 13

what is the liposomal amphotericin B (LAMB) formulation

Answer 13

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

Question 14

what is the amphotericin B lipid complex formulation

Answer 14

amphotericin B complexed with two phospholipids that concentrates in tissues

Question 15

what class is amphotericin B (AMB) and natamycin

Answer 15

polyene antifungal

Question 16

what is natamycin used to treat

Answer 16

fungal keratitis (eye infection)

Question 17

what is the mechanism of action of azole antifungals

Answer 17

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

Question 18

what liver CYP enzymes do azole antifungals impair

Answer 18

CYP3A4

Question 19

what are the systemic azole antifungals

Answer 19

fluconazole
ketoconazole
itraconazole
voriconazole
posaconazole
isavuconazole

Question 20

what fungus is often resistant to fluconazole

Answer 20

Candida Krusei

Question 21

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

Answer 21

fluconazole

Question 22

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

Answer 22

fluconazole

Question 23

Fluconazole brand and uses

Answer 23

Brand: diflucan
uses: candidiasis and cryptococcal meningitis

Question 24

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

Answer 24

ketoconazole

Question 25

what causes decreased absorption of ketoconazole in HIV patients

Answer 25

achlorhydria (absent/low stomach acid)

Question 26

ADR and black box warning for ketoconazole

Answer 26

many drug interactions BBW for hepatotoxicity

Question 27

Itraconazole brand and uses

Answer 27

brand: Sporanox uses: blastomycosis, candidiasis, histoplasmosis

Question 28

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

Answer 28

itraconazole

Question 29

does the oral solution or capsule of itraconazole have superior bioavailability

Answer 29

oral solution

Question 30

major contraindication for use of itraconazole

Answer 30

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

Question 31

voriconazole brand and uses

Answer 31

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

Question 32

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

Answer 32

cyclodextrin

Question 33

ADR of voriconazole

Answer 33

visual disturbance

Question 34

posaconazole brand and uses

Answer 34

brand: noxafil uses: aspergillosis and candidiasis

Question 35

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

Answer 35

posaconazole

Question 36

isavuconazole formulation, brand and uses

Answer 36

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

Question 37

what is flucytosine and its mechanism

Answer 37

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

Question 38

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

Answer 38

due to rapid development of resistance

Question 39

uses for flucytosine

Answer 39

candidiasis and cryptococcosis -high CSF concentration for treating fungal meningitis

Question 40

ADR and drug interactions of flucytosine

Answer 40

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

Question 41

what is the use for Griseofulvin antifungal

Answer 41

tinea infections only

Question 42

what are 3 echinocandins and the brands

Answer 42

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

Question 43

coverage of echinocandins

Answer 43

candida including fluconazole resistant c.krusei and c.glabrata

Question 44

mechanism of action of echinocandins

Answer 44

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

Question 45

3 advantages of echinocandins

Answer 45

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

Question 46

2 disadvantages to echinocandins

Answer 46

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