Antifungals

Question 1

What are the three types of antifungals?

Answer 1

1) Those against dermatophytes (like ring worm)
2) Those against yeasts
3) Those against systemic mycoses.

Question 2

Dermatophytes can be treated both topically and systemically. T/F

Answer 2

True

Question 3

What are some topical treatments for dermatophytes?

Answer 3

Lime-sulfur, azoles, thiabendazole, chlorhexadine, and iodine.

Question 4

What are some systemic treatments for dermatophytes used for?

Answer 4

Onychomycosis (fungal nail infections), multifocal lesions, and in animals were topical treatment is impractical.

Question 5

How does Griseofulvin work?

Answer 5

Disrupts the mitotic spindle microtubular structure, arresting metaphase. Effective ONLY on dermatophytes.
GIven orally, and absorption is increased if given with a fatty meal.
2 types: microsized and ultra-microsized.

Question 6

What are some adverse reactions to Griseofulvin?

Answer 6

Hematologic - bone marrow supression.
GI upset
Teratogen - NEVER give to pregnant animals.

Question 7

For how long do we treat with Griseofulvin?

Answer 7

3-4 weeks, but sometimes up to 12.

Onychomycosis treatment could be as long as 4-6 months.

Question 8

Public health concerns with Griseofulvin?

Answer 8

Not to be administered to food animals.

Question 9

What azoles can be used as systemic treatments for dermatophytes?

Answer 9

Terbinafine and Lufenuron.

Lufenuron is a flea treatment, but can be used as a preventative for fungi.

Question 10

What routes of administration can be used for yeast therapy?

Answer 10

Topically, orally, or vaginally.

Question 11

What is the site of action for Fluorocytosine (5-FC)?

Answer 11

Inhibits DNA and RNA synthesis via conversion of 5-fluorocytosine to 5-fluorouracil.

Question 12

How is 5-FC eliminated?

Answer 12

Renal

Question 13

What is 5-FC mainly used for?

Answer 13

Cryptoococcal meningitis in cats.

Question 14

What are some adverse effects of 5-FC?

Answer 14

Bone marrow suppression
GI side effects
Hepatic toxicity.

Question 15

What is the site of action for Amphotericin B?

Answer 15

Interrupts sterol synthesis in the cell membrane, resulting in leakage. Not very good for CNS infections.

Question 16

Is Amphotericin B fungicidal or fungistatic?

Answer 16

Fungicidal!

Question 17

Aspergilus is commonly resistant against Amphotericin B. T/F

Answer 17

True!

Question 18

What route of administration is used for Amphotericin B?

Answer 18

IV ONLY

Question 19

What are some adverse effects of Amphotericin B?

Answer 19

Cumulative nephrotoxicity via intense vasoconstriction leading to ischemic injury.

Question 20

How is Amphotericin B eliminated?

Answer 20

Hepatic

Question 21

What are the other formulations of Amphotericin B and what is their benefit?

Answer 21

Lipid-based and decrease kidney damage.

Question 22

What is the site of action for azoles?

Answer 22

Azoles impair the synthesis of ergosterol (like Amphotericin B).

Question 23

Are azoles fungicidal or fungistatic?

Answer 23

Fungistatic.

Question 24

Ketoconazole:

Answer 24

Oral administration ONLY
Poor CNS penetration
Slow onset of action.
RARE hepatotoxicity. Primary side effects are GI related.
Inhibits testosterone and cortisol production.

Question 25

Itraconazole:

Answer 25

Orally or IV admin, but oral is better.
Absoprtion enhanced by food and low gastric pH.
More rapid onset than ketoconazole.
Better penetration but still subtherapeutic in the CNS.

Question 26

Fluconazole:

Answer 26

IV and orally.
Similar to Itraconazole in regards to onset.
WIDE tissue distribution - will enter urine, eye, and CNS.

Question 27

Posaconazole:

Answer 27

Oral absorption enhanced by food.

Expensive, so limited use in vet med.

Question 28

Voriconazole:

Answer 28

Active against aspergillus.
IV or oral admin.
Distributes throughout CNS, urine, and in the eye.
Fatty diet may decrease absorption, unlike other azoles.

Question 29

Iodides are the most effective antifungal. T/F

Answer 29

False. Iodides are one of the lease effective antifungals, but they have many other uses. Only sporotrichosis is responsive to iodide therapy.