Antifungals

Question 1

Terbinafine MOA

Answer 1

Fungicidal, inhibits sqalene epoxidase, which leads to toxic accumulation of squalene.

Question 2

-azoles MOA Ex. Fluconazole

Answer 2

Binds fungal P450 enzyme (Erg11), blocking the production of the membrane protein ergosterol and causing the accumulation of lanosterol. Are Fungostatic.

Question 3

Caspofungin MOA

Answer 3

Cell wall inhibitor blocks synthesis of Beta-D-glucan polysachharide. Fungicidal

Question 4

Flucytosine MOA

Answer 4

Inhibits the synthesis of DNA and RNA, prevents purine synthesis. Fungistatic

Question 5

Amphotericin B

Nystatin MOA

Answer 5

Binds ergosterol, creating holes in the membrane allowing leakage of electrolytes. It is fungicidal.

Question 6

Griseofulvin MOA

Answer 6

Binds microtubules, inhibiting spindle leading to multinucleate cells, Fungistatic

Question 7

Terbinafine Spectrum

Answer 7

Broad- Amphotericin is used for invasive systemic fungal infections in immunocompromised patients, active against yeast and molds. Nystatin is too toxic to use systemically but treats the same as amphotericin but on skin.

Question 8

Terbinafine Distribution

Answer 8

Small fraction of drug is excreted, so has a long half life. Liposomal form can cross the BBB.

Question 9

Terbinafine Adverse Effects

Answer 9

Nystatin is for topical use only, binds to cholesterol, and decreases renal blood flow and can lead to permanent destruction of the basement membrane, 80% of patients experience nephrotoxicity.

Question 10

Terbinafine Resistance

Answer 10

Rare, results in decreased ergosterol in the membrane

Question 11

-azoles Ex. Fluconazole Spectrum

Answer 11

Most widely used agent and spectrum varies by agent

Question 12

-azoles Ex. Fluconazole Distribution

Answer 12

Orally available, substrate for efflux pump in brain.

Question 13

-azoles Ex. Fluconazole Toxicity

Answer 13

Drug-Drug Interactions, hepatotoxicity, neurotoxicity, alters hormone synthesis, avoid during pregnancy

Question 14

-azoles Ex. Fluconazole Resistance

Answer 14

Altered CYP450, upregulation of efflux transporters

Question 15

Allylamines- Terbinafine Spectrum

Answer 15

Dermatophytes (cause fungal infections of the skin and nails)

Question 16

Allylamines- Terbinafine Toxicity

Answer 16

Topical, drug interactions with CYP2D6 substrates

Question 17

Allylamines- Terbinafine Resistance

Answer 17

Rare in human pathogens but could include decreased uptake, mutant binding site, and substrate for efflux transporters.

Question 18

Flucytosine Spectrum

Answer 18

Candida albicans and Cryptococcus

Question 19

Flucytosine Distribution

Answer 19

Oral, penetrates CNS

Question 20

Flucytosine Toxicity

Answer 20

Only partially selective for yeast can lead to bone marrow suppression-follow patient’s cell counts closely

Question 21

Flucytosine Resistance

Answer 21

Loss of converting enzyme or transporters, often cotreat with amphotericin B to increase uptake and minimize likelihood of developing resistance

Question 22

Griseofulvin Spectrum

Answer 22

Dermatophyres (greater uptake)

Question 23

Griseofulvin Distribution

Answer 23

Lipids increase oral absorbtion and then concentrates in dead keratinized layer of the skin

Question 24

Griseofulvin Resistance

Answer 24

Change in Beta-Tubulin, need to take orally for months so if patient is not adherant, resistance is more likely to develop.

Question 25

Griseofulvin Toxicity

Answer 25

Teratogenic

Question 26

Caspofungin Spectrum

Answer 26

Fungicidal-Candida and Fungistatic-Aspergillus

Question 27

Caspofungin Distribution

Answer 27

IV dosage, Large molecular weight, no CNS entry

Question 28

Caspofungin Toxicity/ resistance

Answer 28

Fever, rash at site of injection no known resistance yet.