Antifungal Agents

Question 0

Antifungal agent that is nucleic acid synthesis inhibitor

Answer 0

flucytosine

Question 1

Fungal cell membrane- Fungi use _____________; mammals use cholesterol

Answer 1

Ergosterol

Question 2

MOA of flucytosine:
A) Actively transported into fungal cells by ______ permease.
B) Converted to ______________ by cytosine deaminase
C) 5-FU is converted to ____________ acid and FUTP.
D) Action is ____________

Answer 2

Cytosine, 5-fluorouracil (5-FU), 5-fluordeoxyuridylic, fungistatic

Question 3

Antifungal agent: Mitosis Inhibitor

Answer 3

Griseofulvin

Question 4

MOA of griseofulvin

Answer 4

Binds to tubulin, thereby disrupting assembly of the mitotic spindle; action is fungistatic.
-Accumulates in keratin precursor cells and allows new growth of skin, hair, and nails to be free of fungal infection

Question 5

Antifungal: Squalene epoxidase Inhibitor

Answer 5

Terbinafine

Question 6

MOA of Terbinafine

Answer 6

Prevents conversion of squalene to lanosterol, which is precursor to ergosterol- fungicidal

Question 7

14a-sterol Demethylase Inhibitors- Azoles

Answer 7

Prototype triazole- itraconazole

Question 8

A fungistatic drug that prevents conversion of lanosterol to ergosterol by causing destabilization of the cell membrane and associated enzymes and increased permeability

Answer 8

Itraconazole- all inhibit 14a-sterol demethylase

Question 9

Inhibitors of Fungal membrane stability

Answer 9

Amphotericin B and Nystatin

Question 10

MOA of amphotericin B and nystatin

Answer 10

Forms pores in membrane; allows leakage of cellular contents (K+); action is fungistatic or fungicidal depending on concentration and fungal sensitivity

Question 11

Inhibitors of fungal cell wall synthesis

Answer 11

caspofungin

Question 12

Resistance to flucytosine develops how

Answer 12

during therapy when used alone; due to mutations of permease and deaminase

Question 13

What drug is this: Narrow spectrum agent used to treat systemic candidiasis, cryptococcus neoformans infections, and aspergillus. Usually administered in combination with amphotericin B to increase uptake.

Answer 13

Flucytosine

Question 14

Flucytosine is ________ absorbed and well distributed; dose reduction is necessary in _________ insufficiency

Answer 14

Orally, renal

Question 15

Adverse rxns of Flucytosine

Answer 15

Hematologic- bone marrow suppression

Hepatoxicity- mild, reversible

Question 16

Flucytosine can inhibit which enzyme

Answer 16

CYP3A4

Question 17

True/False: Griseofulvin is not active against Candida sp. and is not useful in systemic mycoses

Answer 17

True

Question 18

Adverse rxns of griseofulvin

Answer 18

Headaches are common. Can precipitate attacks of acute porphria in susceptible patients

Question 19

Name this drug: Topical use for ringworm infections caused by dermatophytes; less active against Candida sp. Oral use treatment for onychomycosis of toe and fingernails.

Answer 19

Terbinafine

Question 20

Adverse rxns of terbinafine

Answer 20

Skin rxns (cutaneous lupus, SJS) and disturbances to taste. Hepatotoxicity (rare).

Question 21

What drug is a broad spectrum agent used topically or orally against many pathogenic fungi? Systemic mycoses (blastomycoses, histoplasmosis, aspergillosis, others) and superficial mycoses (dermatophytes and Candida yeast infections)

Answer 21

Itraconazole

Question 22

What antifungal drug class has several drug interaction due to inhibition of human CYPs which can result in serious toxicity.

Answer 22

14a-Sterol Demethylase Inhibitors-Azoles (itraconazole)

Question 23

T/F: Itraconazole can cause hypotension, hyperkalemia and edema; cardiac suppression. Should be avoided during pregnancy.

Answer 23

False: Itraconazole can cause hypERtension, hypOkalemia and edema; cardiac suppression. Should be avoided during pregnancy.

Question 24

What class of antifungal drugs is broad spectrum agent useful for nearly all life-threatening systemic mycoses including cryptococcal meningitis but then should be replaced by an azole for long term therapy?

Answer 24

Inhibitors of Fungal Membrane stability (Amphotericin B, nystatin)

Question 25

What would you use for the “swish and swallow” treatment for oral thrush

Answer 25

Nystatin

Question 26

What class of drugs has these adverse rxns (except when topically or orally used):

1) Infusion related effects- cytokine storm
2) Renal toxicity
3) Hematologic toxicity

Answer 26

Inhibitors of Fungal Membrane stability (Amphotericin B, nystatin)

Question 27

Inhibitors of cell wall synthesis fungi

Answer 27

caspofungin

Question 28

MOA of caspofungin

Answer 28

non-competitive inhibitors of B-(1,3)-D-glucan synthesis; disrupts cell wall integrity resulting in osmotic stress and cell lysis; action is fungicidal

Question 29

Therapeutic uses and adverse effects of caspofungin

Answer 29

IV therapy of deeply invasive aspergillosis in patients unresponsive or intolerant to traditional agents; and systemic candidiasis. Only side effect is release of histamine with too rapid infusion.