32 - Antifungal Drugs (Quelle)

Question 1

most common type of mucocutaneous oral and genital fugal infection

Answer 1

candidiasis

Question 2

fungus most often associated with oral lesions (thrush, denture stomatitis)

Answer 2

candida albicans

Question 3

2 categories of antifungal drugs

Answer 3

systemic infections-oral and parenteral

superficial and mucocutaneous infections-topical and oral

Question 4

polyene antibiotics

Answer 4

amphotericin B and nystatin

Question 5

amphotericin B drug of choice for what

Answer 5

broadest spectrum

most life threatening systemic fungal infections

Question 6

amphotericin b cidal or static

Answer 6

cidal

Question 7

mechanism of amphotericin b

Answer 7

binds to ergosterol (cell membrane)
makes pore-alters permeability
leakage of Na, K, H
cell death-cidal

Question 8

selective toxicity of amphotericin b

Answer 8

mammalian cell membranes have cholesterol

Question 9

fungal resistance of amphotericin b

Answer 9

when binding of drug to ergosterol is impaired

• decreased ergosterol concentration from azoles
• ergosteroles affinity is reduced
• rare but seen in candida species

Question 10

amphotericin b pharmacokinetics

Answer 10

poorly absorbed from GI and skin-topically for candida
used parenterally for systemic infections
slow IV infusion

Question 11

metabolism of amphotericin b

Answer 11

kidney

Question 12

adverse effects of amphotericin b

Answer 12

topical-local irritation
immediate reaction-fever, chills, muscle spasm, vomiting, headache, hypotension, allergic reaction : slow dose or decrease dose
nephrotoxicity

Question 13

most important side effect of amphotericin b

Answer 13

nephrotoxicity

Question 14

drug interactions with amphotericin b

Answer 14

digitalis- induced hypokalemia
azoles-inhibitors of ergosterol synthesis, amphtericin b resistance
Nephrotoxic agents

Question 15

nystatin use

Answer 15

similar to amphotericin b
narrower spectrum
too toxic for parenteral use
not well absorbed

Question 16

nystatin pharmacokinetics

Answer 16

topically for candidal infections of mucosa, skin, GI, vagina
**THRUSH

Question 17

nystatin adverse effects

Answer 17

bitter taste

Question 18

griseofulvin mechanism

Answer 18

interacts with microtubules to block fungal mitosis

Question 19

griseofulvin use

Answer 19

fungistatic
oral
treatment of dermatophytosis (hair, skin, nails)

Question 20

griseofulvin adverse effects

Answer 20

induces CYP isoforms

alters pharmacologic effectiveness of drugs

Question 21

flucytosine mechanisms

Answer 21

enzyme cytosine deaminase converts it to 5-fu

inhibits fungal DNA and protein synthesis

Question 22

flucytosine uses

Answer 22

orally
candida and cryptococcus
fungistatic

Question 23

selective toxicity of flucytosine

Answer 23

human cells cant convert to 5-fu

Question 24

flucytosine must be used with

Answer 24

amphotericin b

Question 25

flucytosine pharmacokinetics

Answer 25

excellent oral bioavailability CNS penetration (meningitis) renal excretion

Question 26

flucytosine adverse effects

Answer 26

GI intolerance | depress bone marrow (anemia, leukopenia, thrombocytopenia)

Question 27

imidazoles

Answer 27

2 N atoms miconazole clotrimazole

Question 28

triazoles

Answer 28

``` 3 N atoms fluconazole itraconazole voriconazole posaconazole efinaconazole ```

Question 29

azole mechanism

Answer 29

inhibition of ergosterol synthesis by blocking CYP enzyme (lanosterol 14-a demethylase) impair membrane synthesis

Question 30

azole uses

Answer 30

oral and parenterally | fungistatic

Question 31

azole resistance

Answer 31

reduced drug concentration reduced affinity for target enzyme up regulation of target enzyme

Question 32

miconazole uses

Answer 32

limited by toxicity effective topically against cutaneous candidiasis jock itch, ring worm, athletes foot, vaginal infections, thrush

Question 33

clotrimazole uses

Answer 33

oral/topical | oropharyngeal candidiasis in AIDS patients

Question 34

itraconazole uses

Answer 34

broader spectrum than fluconazole absorbed well from GI (oral) and IV treat aspergillus and fluconazole resistant candida

Question 35

fluconazole uses

Answer 35

oral, IV CNS penetration (crytpococcus meningitis) candida NOT effective against aspergillus

Question 36

voriconazole

Answer 36

oral, IV | treatment of invasive mold (aspergillosis)

Question 37

voriconazole adverse effects

Answer 37

visual side effects skin rash drug interactions (inhibits CYP 3A4) increased risk for zygomycosis

Question 38

posaconazole uses

Answer 38

``` oral treat zygomycosis (rhizopus, mucor) prophylaxis of invasive fungal infections in BMT, malignancies with prolonged neutropenia ```

Question 39

posaconazole adverse effects

Answer 39

drug interactions skin rash elevated hepatic enzymes

Question 40

efinaconazole uses

Answer 40

treatment of onychomycosis

Question 41

allylamines mechanisms

Answer 41

inhibit ergosterol synthesis by blocking squalene epoxidase | fungicidal

Question 42

terbinafine uses

Answer 42

``` (allylamine) topical or oral use against dermatophytes skin/nail infections refractory mold infections accumulates in skin, nails, fatty tissues ```

Question 43

echinocandins examples

Answer 43

caspofungin | micafungin

Question 44

echinocandin mechanism

Answer 44

inhibit glucan synthesis weaken cell wall lysis=cidal

Question 45

echinocandin uses

Answer 45

IV | aspergillus, azole resistant candida