Antifungals

Question 1

Amphotericin B and Nystatin belong to the same class of antifungal. Why can Nystatin not be used for systemic infections?

Answer 1

Nystatin is too toxic for use in systemic infections. The drug is used topically for the treatment of cutaneous or mucocutaneous candidiasis.

Question 2

What infections are generally treated with Itraconazole?

Answer 2

Dermatophyte infections & onychomycosis (nail infections)

Question 3

What is the target and mechanism of action of Flucytosine?

Answer 3

Targets nucleic acid synthesis - the drug resembles cytosine and enters the cell via a cytosine permease. The drug is phosphorylated by a fungal enzyme and then inhibits RNA or DNA synthesis.

Question 4

Terbinafine belongs to what class of antifungals? What fungi is the drug used to treat?

Answer 4

Allylamine - used primarily for dermatophyte infections and onychomycosis (infection of nails)

Question 5

A patient is diagnosed with meningitis due to a fungal infection. What drug would provide maintenance therapy due to its ability to enter the CNS?

Answer 5

Fluconazole

Question 6

What drug can be used to treat both invasive aspergillus & mucormycosis?

Answer 6

Isavuconazole

Question 7

Flucytosine is not used as monotherapy due to potential resistance. What other antifungals are used in combination with Flucytosine?

Answer 7

Amphotericin B or Fluconazole

Question 8

Posaconazole is commonly used to treat infections caused by what bacteria?

Answer 8

Mucormycetes

Question 9

Griseofulvin may be used to treat infections by what fungi?

Answer 9

Microsporum, Trichophyton, & Epidermophyton (dermatophyte
infections)

Question 10

What are the commonly used Triazoles?

Answer 10

Fluconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole

Question 11

What fungal cell components serve as targets of antifungals?

Answer 11

Cell wall, cell membrane, nucleic acid synthesis, microtubules for cell division

Question 12

What is the target of Echinocandins?

Answer 12

Target the cell wall by inhibiting the b-glucan synthase. This disrupts the osmotic environment, cell growth, and cell division

Question 13

What is Amphotericin B?

Answer 13

A major antifungal belonging to the Polyene class of drugs. The drug has broad-spectrum use and is often used to treat systemic infections. Renal impairment is a potential side effect.

Question 14

What antifungals target ergosterol synthesis?

Answer 14

Allylamines, Azoles, Polyenes

Question 15

What class of antifungal targets cell membrane synthesis by inhibiting the lanosterol 14-a-demethylase, but may cause drug interactions due to binding the Cytochrome P-450-dependent enzyme?

Answer 15

Azoles

Question 16

What are the two types of Azole drugs?

Answer 16

Imidazoles & Triazoles - differ by the number of Nitrogens in the azole ring

Question 17

What is the most commonly used imidazole? What is the drug typically used to treat?

Answer 17

Ketoconazole - used to treat cutaneous infections, dimorphic mycoses, & Cryptococcus neoformans

Question 18

Allylamines target the cell membrane. What is their mechanism of action?

Answer 18

Inhibit the squalene epoxidase, a step in ergosterol synthesis. This leads to decreased ergosterol and increased squalene in the membrane. Squalene is toxic to the cell.

Question 19

How do Imidazoles differ from Triazoles?

Answer 19

Triazoles have 3N in the azole ring, as opposed to 2N. They also have a greater affinity for the fungal cytochrome P-450 enzyme, resulting in fewer side effects.

Question 20

A patient is diagnosed with invasive aspergillus. What is the first choice antifungal for treatment?

Answer 20

Voriconazole

Question 21

What antifungals pose a risk for drug-drug interactions due to interactions with the cytochrome P-450 enzyme?

Answer 21

Azole drugs & Griseofulvin

Question 22

Against what fungi are Echinocandins useful?

Answer 22

Candida & Aspergillus

Question 23

Griseofulvin is fungistatic. What is the drug’s mechanism of action?

Answer 23

Inhibits the assembly of microtubules and prevents the formation of the mitotic spindle

Question 24

Polyenes are fungicidal. What is their mechanism of action?

Answer 24

Bind to ergosterol making the membrane leaky and resulting in cell death

Question 25

What are the 5 classes of antifungal drugs?

Answer 25

Echinocandins, Allylamines, Azoles (Imidazoles & Triazoles), Polyenes, Flucytosine