Le33.Antifungals

Question 1

What is the MOA of Amphotericin B?

Answer 1

Binds to ergosterol in fungal cell membranes, leading to formation of pores and cell death =fungicidal

Question 2

Due to ergosterol’s similarity to cholesterol, amphotericin B drugs may bind to cholesterol, disrupting human cell membranes, when is this seen? What are the major side affects?

Answer 2

B/c amphotericin B is such a large molecule it is not absorbed into the blood stream if taken orally, thus only ween when given IV (Amphotec). Fever, chills, headache, nausea, hypotension. Big One = Nephrotoxicity (DLT)

Question 3

When is fungizone used? Route of administration?

Answer 3

Fungizone is used as a topical agent (troche & mouth rinse) for oral and GI infections. No systemic use.

Question 4

When is Amphotec used?

Answer 4

Amphotec is the intravenous formulation of amphotericin B and is used to treat potentially life threatening systemic fungal infections.

Question 5

What advancement has made the use of amphotec much safer?

Answer 5

Liposomal formulation, where amphotericin has a greater affinity for the liposome than it does for cholesterol, but less affinity for the liposome than ergosterol.

Question 6

What is the Dose Limiting Toxicity of amphotec?

Answer 6

Nephrotoxicity, which causes leucopenia, thrombocytopenia, anemia and anaphylactic rxns

Question 7

When is Nystatin used? Route of administration?

Answer 7

Nystatin is used for oral fungal infections (will likely prescribe) and is given as a topical ointment, rinse or lozenge.

Question 8

Why might Clotrimazole be prescribed for oral/pharyngeal candidiasis over Nystatin?

Answer 8

Clotrimazole lacks the bitter taste of nystatin, which generally leads to better patient compliance

Question 9

MOA of Flucytosine?

Answer 9

Flucytosine is a prodrug that is converted to 5-FU, which disrupts fungal RNA & inhibits protein synthesis

Question 10

Flucytosine’s active intermediate, 5-FU, is a toxic cancer therapeutic agent, with this information, what is the likely major toxic side affect?

Answer 10

Bone marrow suppression leading to anemia, leucopenia & thrombocytopenia

Question 11

When is Griseofulvin used? Route of administration?

Answer 11

Griseofulvin is used for long standing dermatophytic infections of the skin, scalp & NAILS. Taken orally.

Question 12

MOA of griseofulvin?

Answer 12

Interferes with mitotic cell division by disrupting the mitotic spindle.

Question 13

What is a major contraindication of griseofulvin? Why?

Answer 13

Contraindicated in pts with acute intermittent porphyria. Griseofulvin is a P-450 inducer, which increases hepatic production of porphyrin rings.

Question 14

When is griseofulvin best absorbed?

Answer 14

When taken with fatty foods.

Question 15

What is the MOA of Azole antifungal drugs?

Answer 15

Azoles inhibit fungal P-450, which blocks the conversion of lanosterol to ergosterol.

Question 16

What is the major Azole drug interaction that you should be aware of?

Answer 16

Fluconazole, an otherwise well tolerated drug, with Warfarin. Due to CYP-2c9 inhibition, major increases in warfarin levels may occur.

Question 17

Fluconazole is the most prescribed azole drug, what are its major uses(2)?

Answer 17

1. Oropharyngeal and esophageal candidiasis, especially in AIDS pts.
2. Fungal infections in the brain and spinal cord due to its ability to penetrate the BBB into the CNS

Question 18

Why should Ketoconazole be avoided if possible?

Answer 18

B/c ketoconazole has the greatest affinity for human CYP-3A4, which means it has the highest number of adverse drug rxns.

Question 19

When is clotrimazole used?

Answer 19

To tx vaginal candidiasis (cream) and oral/pharyngeal candidiasis (troche)