Antifungal therapy

Question 1

Amphotericin B: mech

Answer 1

Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes.
Amphotericin "tears" holes in fungal membrane forming pores

Question 2

Amphotericin B: uses

Answer 2

Serious, systemic mycoses.
Cryptococcus (with/w/out flucytosine for meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor.
Intrathecally for fungal meningitis.
Supplement K+ and Mg2+ because of altered renal tubule permeability

Question 3

Amphotericin B: tox

Answer 3

Fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (“amphoterrible”). Hydration decreases nephrotoxicity. Liposomal amphotericin decreases toxicity.

Question 4

Nystatin: mech

Answer 4

Same as amphotericin B. Topical form because too toxic for systemic use.

Question 5

Nystatin: use

Answer 5

“Swish and swallow” for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.

Question 6

Azoles:

Answer 6

Fluconazle, ketoconazle, clotrimazole, miconazole, itraconazole, voriconazole.

Question 7

Azoles mech:

Answer 7

Inhibits fungal sterol (ergosterol) synthesis, by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol. (14-alpha demethylase)

Question 8

Azoles: use

Answer 8

Local and less serious systemic mycoses.
Fluconazole: chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types.
Itraconzale: Blastomyces, Coccidioides, Histoplasma.
Clotrimazole and Miconazle for topical fungal infections

Question 9

Azoles tox:

Answer 9

Testosterone synthesis inhibition (gynecomastia, esp with ketoconazole), liver dysfunction (inhibits cytochrome P-450)

Question 10

Flucytosine: mech

Answer 10

Inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase

Question 11

Flucytosine: use

Answer 11

Systemic fungal infections (esp meningitis by Cryptococcus) in combo with Amphotericin B.

Question 12

Flucytosine: tox

Answer 12

Bone marrow suppression

Question 13

Echinocandins:

Answer 13

Caspofungin, micafungin, anidulafungin

Question 14

Echinocandins: mech

Answer 14

Inhibits cell wall synthesis by inhibiting synthesis of Beta-glucan.

Question 15

Echinocandins: use

Answer 15

Invasive asperillosis, Candida

Question 16

Echinocandins: tox

Answer 16

GI upset, flushing (by histamine release)

Question 17

Terbinafine: mech

Answer 17

Inhibits fungal enzyme squalene epoxidase (decreases ergosterol synthesis)

Question 18

Terbinafine: use

Answer 18

Dermatophytoses (esp onychomycosis - funga infection of finger or toe nails)

Question 19

Terbinafine: tox

Answer 19

GI upset, HA, hepatotoxicity, taste disturbance

Question 20

Griseofulvin: mech

Answer 20

Interferes with MT formation; disrupts mitosis. Deposits in keratin-containing tissues (nails)

Question 21

Griseofulvin: use

Answer 21

Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)

Question 22

Griseofulvin: tox

Answer 22

Teratogenic, carcinogenic, confusion, HA, increase P-450 and warfarin metabolism, GI
Avoid sunlight