Antifungal agents

Question 1

What are fungi

Answer 1

eukaryotic organisms growing as single cells (yeasts) or as filamentous multicellular aggregates (molds)

Question 2

dimorphic fungi

Answer 2

can grow as yeasts (oval or round) in host and molds (hyphae) at room temperature in vitro

Question 3

examples of dimorphic fungi

Answer 3

sporotrichosis
coccidioidomycosis
paracoccidioidomycosis
chromoblastomycosis
blastomycosis
histoplasmosis

Question 4

Cells of fungi that are pathogenic in humans are

Answer 4

nonmotile and have a rigid cell wall, usually containing chitin and polysaccharides

Question 5

Mycoses are generally not transmissible except for

Answer 5

ringworm

thrush in newborn from candida albicans during childbirth

Question 6

Dermatomycoses

Answer 6

filamentous fungi that live on keratinized tissue

itching, burning and cracking of skin

Question 7

Onychomycoses

Answer 7

localized fungal infection of nail or nail bed

Question 8

Examples of systemic infections by yeast-like fungi

Answer 8

histoplasmosis and candidiasis

Question 9

Drugs used to treat dermatomycoses

Answer 9

1. Tolnaftate
2. Clotrimazole
3. Griseofulvin

Question 10

MOA of tolnaftate

Answer 10

inhibits fungal squalene epoxidase, resulting in decreased ergosterol biosynthesis

Question 11

What is ergosterol?

Answer 11

the steroid present in fungal cell membranes

Question 12

Why is inhibition of ergosterol biosynthesis not cytotoxic to the host?

Answer 12

mammalian cells contain cholesterol in the cell membranes not ergosterol and fungal squalene epoxidase is more sensitive to tolnaftate than mammalian squalene epoxidase

Question 13

Other squalene epoxidase inhibitors used as antifungal agents

Answer 13

terbinafine
naftifine
butenafine

Question 14

The azole class of antifungals inhibit

Answer 14

cytochrome P450

Question 15

cytochrome P450 catalyzes

Answer 15

the 14a-demethylation of lanosterol during its conversion to ergosterol

Question 16

What does clotrimazole inhibit

Answer 16

the binding and activation of molecular oxygen by cytochrome P450 and therefore inhibits the conversion of lanosterol to ergosterol

Question 17

Describe the selectivity of clotrimazole to human cytochrome P450

Answer 17

azoles have a greater affinity for the fungal cytochrome P450 than the human one, but the azoles still do bind to human cytochrome P450 and can inhibit drug metabolism

Question 18

Other examples of azole antifungal agents

Answer 18

miconazole and ketoconazole

Question 19

How does Griseofulvin work?

Answer 19

disrupts the mitotic spindle by binding to polymerized microtubles to inhibit mitosis

Question 20

What is griseofulvin used to treat?

Answer 20

used in the treatment of onychomycosis

deposited in newly formed keratin, where it prevents fungal growth

Question 21

What kind of diet can increase the absorption of griseofulvin?

Answer 21

high fat diet

Question 22

Adverse effects of griseofulvin?

Answer 22

photosensitivity, hypersensitivity and headache

Question 23

Antifungals to treat systemic infections

Answer 23

1. Amphotericin B
2. 5-Fluorocystosine
3. Ketoconazole
4. Fluconazole
5. Itraconazole
6. Echinocandins

Question 24

Describe the structure of Amphotericin B

Answer 24

amphoteric

lipophilic polyene region and a hydrophilic polyalcohol region

Question 25

Side effects of amphotericin B

Answer 25

fever and chills | sometimes headache, nausea, vomiting, nephrotoxicity and hypotension

Question 26

Major limiting toxicities of amphotericin B

Answer 26

nephrotoxicity and hypokalemia

Question 27

drug of choice for life threatening fungal infections

Answer 27

Amphotericin B

Question 28

Amphotericin B used to treat

Answer 28

deep mycoses including aspergillosis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis and mucormycosis

Question 29

MOA of amphotericin B

Answer 29

binds to ergosterol in membranes of sensitive fungi, opening pores and allowing leakage of ions and small organic molecules

Question 30

MOA of 5-fluorocytosine

Answer 30

susceptible fungi convert 5-fluorocytosine to 5-fluorouracil, which is converted into 5-fluorodeoxyuridine monophosphate

Question 31

What does 5-fluorodeoxyuridine monophosphate inhibit

Answer 31

thymidylate synthase - thus inhibiting DNA biosynthesis

Question 32

5-fluorouracil incorporation into RNA in place of uracil does what

Answer 32

leads to the inhibition of protein synthesis

Question 33

5-fluorouracil functions as a

Answer 33

antimetabolite (analog of an essential substrate that is accepted by the metabolic pathway but cannot itself support the life of the cell)

Question 34

5-fluorocytosine (flucytosine) is used to treat?

Answer 34

used in combination with amphotericin B to treat systemic Candida infections and Cryptococcus neoformans meningitis

Question 35

Spectrum of activity for 5-fluorocytosine

Answer 35

limited to susceptible strains of Candida, Cryptococcus, Torulopsis glabrata, Cladosporium and Aspergillus

Question 36

Toxicity of 5-fluorocytosine

Answer 36

depresses bone marrow funciton (leukopenia and thrombocytopenia) monitor kidney function nausea, vomiting, diarrhea, rash and enterocolitis

Question 37

Ketoconazole used for

Answer 37

oral treatment of systemic infections | tolerated better than AmpB but less effective

Question 38

Ketaconazole treats

Answer 38

blastomycosis, histoplasmosis, coccidioidomycosis and paracoccidioidomycosis

Question 39

fluconazole used to treat

Answer 39

IV infusion to treat cryptococcal meningitis in AIDS patients prevention of relapse of cryptococcal meningitis in AIDS patients oral dose for treatment of vaginal candidiasis

Question 40

Toxicity of fluconazole

Answer 40

rare cases of hepatotoxicity

Question 41

Therapeutic uses of itraconazole

Answer 41

preferred treatment over ketoconazole for the treatment of nonmeningeal histoplasmosis (does not penetrate CSF) AIDS patients with disseminated histoplasmosis

Question 42

Serious side effects of itraconazole

Answer 42

heart failure | rare severe hepatotoxicity

Question 43

coadministration of itraconazole is contraindicated with

Answer 43

cisapride, pimozide, quinidine and dofetilide

Question 44

Echinocandins inhibit

Answer 44

1,3-beta-glucan synthesis in the fungal cell walls by noncompetitive inhibition of 1,3-beta-glucan synthase

Question 45

Describe use of echinocandins

Answer 45

broad spectrum antifungal agents that have no cross-resistance with other antifungals and are synergistic with voriconazole and amphotericine B

Question 46

Adverse reactions of echinocandins

Answer 46

hepatotoxicity and sensitivity/allergic reactions