antifungals

Question 1

potential antifungal targets

Answer 1

membranes (ergosterol), nucleic acids, cell wall

Question 2

drugs used for systemic fungal infections (full list)

Answer 2

amphotericin B, flucytosine, fluconazole, itraconazole, voriconazole, caspofungin

Question 3

effective (brad-spectrum agent) for most serious systemic mycoses, esp life-threatening ones. ONLY use for proven or highly suspected systemic infections

Answer 3

amphotericin B

Question 4

amphotericin B mechanism of action

Answer 4

very lipophilic, inserts into fungal membrane, binds ergosterol, increases pores/leakiness

Question 5

amphotericin side effects

Answer 5

fever, N/V, HA, chills, hypotension, hypokalemia, tachypnea. 90% get nonpermanent nephrotoxicity. total cumulative dose important for reasons of permanent renal toxicity. reversible hypochromic, normocytic anemia

Question 6

used for serious infections (candida, cryptococcus), synergistic with amphotericin B (permits reduction of dose), fungistatic

Answer 6

flucytosine

Question 7

flucytosine mechanism of action

Answer 7

acts on cytosine permease

Question 8

flucytosine side effects

Answer 8

N/V, diarrhea, enterocolitis, leukopenia, thrombocytopenia, reversible elevated hepatic enzymes. use caution with renal insufficiency or bone marrow depression. monitor closely

Question 9

relative to amphotericin, other drugs for serious fungal infections…:

Answer 9

have narrower spectrum of action, not for immediately life-threatening infections, have fewer/less serious side effects

Question 10

triazoles for serious fungal infections (imidazoles also used)

Answer 10

fluconazole, itraconazole, voriconazole

Question 11

MOA for imidazoles and triazoles

Answer 11

inhibit 14-a-sterol demethylase, a fungal cytochrome P450 that converts lanosterol to ergosterol. inhibits ergosterol synthesis –> membrane instability

Question 12

used for cryptococcus (esp after amphotericin therapy), candida at many sites including CNS and urinary, some albicans and galbrata, NOT krusei

Answer 12

fluconazole

Question 13

used for blastomyces, histoplasma, candida (not CNS & urinary), more c. albicans and galbrata

Answer 13

itraconazole

Question 14

used for aspergillus, fusarium, scedosporium, candida (not urinary), covers many candida spp including galbrata and krusei

Answer 14

voriconazole

Question 15

which azole has CNS penetration and has active drug in urine?

Answer 15

fluconazole

Question 16

azole side effects

Answer 16

N/V, rash, diarrhea, headache, mild hepatotoxicity (discontinue with onset of liver dysfunction), inhibit metabolism of several other drugs (CYP 3A and 2C family inhibitors)

Question 17

itraconazole contraindications

Answer 17

DO NOT GIVE with other drugs that are metabolized by CYP 3A4. potential for serious CV events including death

Question 18

which azole has lowest incidence of hepatotoxicity?

Answer 18

fluconazole

Question 19

voriconazole side effects

Answer 19

visual disturbances (30%), rash with photosensitive component

Question 20

antifungal that targets cell wall

Answer 20

caspofungin

Question 21

uses of caspofungin

Answer 21

invasive aspergillus, candida (esophageal and systemic)

Question 22

caspofungin MOA

Answer 22

inhibits fungal cell wall synthesis by noncompetitively blocking synthesis of B(1,3)-D-glucan in filamentous fungi. no cross resistance with azoles

Question 23

caspofungin side effects (based on limited experience)

Answer 23

generally well-tolerated, but fever, N/V, flushing, phlebitis at injection site

Question 24

drugs for treatment of superficial mycoses

Answer 24

nystatin, fluconazole, miconazole, ketoconazole, clotrimazole, itraconazole, natamycin

Question 25

treatment for superficial candidiasis (vaginal, urinary tract, oropharynx)

Answer 25

fluconazole

Question 26

cream/suppository for vaginal candida, causes itching/burning

Answer 26

miconazole

Question 27

topical or oral troche use for candida, not opthalmic. allergic/irritation reactions. oral troches cause?

Answer 27

clotrimazole.

oral troches cause abnormal liver function tests

Question 28

used for oropharyngeal and esophageal candida

Answer 28

itraconazole

Question 29

effective against azole-resistant strains, topical use for candida (not opthalmic), oral for GI candida (can cause GI distress)

Answer 29

nystatin

Question 30

treatment of opthalmic fungal infections

Answer 30

natamycin

Question 31

natamycin toxicity

Answer 31

conjunctival chemosis and hyperemia

Question 32

causative agents for dermatophytic infections

Answer 32

trichyphyton, epidermophyton, microsporum

Question 33

topical treatments for dermatophytes

Answer 33

miconazole, clotrimazole, tolnaftate, terbinafine, ciclopirox

Question 34

only FDA-approved topical rx for mild-to-moderate fungal nail infections

Answer 34

ciclopirox

Question 35

dermatophyte therapy– oral preparations use

Answer 35

sever dermatophyte infections, those that are refractory to topical therapy

Question 36

12-week therapy for nail infections, shorter for other dermatophytic infections

Answer 36

terbinafine

Question 37

terbinafine mechanism of action

Answer 37

blocks squalene epoxidase so squalene (toxic) builds up. fungicidal.

Question 38

terbinafine side effects

Answer 38

diarrhea, dyspepsia, abdominal pain

Question 39

for recalcitrant dermatophytic infections of skin, hair, nails. therapy for kids esp tinea capitis

Answer 39

griseofulvin

Question 40

griseofulvin mechanism

Answer 40

interferes with microtubule function/mitotic spindle/mitosis

Question 41

griseofulvin side effects

Answer 41

low incidence. contraindicated in those with porphyria and advanced liver disease. increased metabolism of several drugs (CYP inducer). use with caution if penicillin allergy.

Question 42

oral 3-month therapy for fungal toenail infections

Answer 42

itraconazole

Question 43

side effects of itraconazole

Answer 43

N/V, rash, diarrhea, headache, edema, inhibits metabolism of many drugs, discontinue with signs of liver dysfunction