Antifungals

Question 1

Amphotercin B mech

Answer 1

Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes. “amphoTERicin ‘tears’ holes in the fungal membrane by forming pores

Question 2

Amphotercin B Clinical Use

Answer 2

Serious, systemic mycoses. Cryptococcus (amphotercin B with/without flucytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor. Intrathecally for fungal meningitis. Supplement K+ and Mg+2 because of altered renal tubule permeability.

Question 3

Amphotercin B Toxicity

Answer 3

Fever/chills (‘shake and bake’), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (‘amphoterrible’).

Question 4

What can decrease the nephrotoxicity of Amphotercin?

Answer 4

Hydration

Question 5

Liposomal amphotercin

Answer 5

decreases toxicity

Question 6

Nystatin Mech

Answer 6

Same as amphotercin B.

Question 7

Is Nystatin Oral, IV, IM Topical, Inhaled?

Answer 7

Topical! too toxic for systemic use

Question 8

Nystatin clinical use

Answer 8

‘Swish and Swallow’ for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis

Question 9

What are the Azoles?

Answer 9

Fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole

Question 10

Mech of Azoles

Answer 10

Inhibit fungal sterol (ergosterol) synthesis, by inhibiting the CYP-450 enzyme that converts lanosterol to ergosterol

Question 11

Clinical use of Azoles

Answer 11

Local and less serious systemic mycoses

Question 12

Which Azole is used for chronic suppression of cryptococcal meningits in AIDS patients and candidal infections of all types?

Answer 12

Fluconazole

Question 13

Which Azole do you treat Blastomyces, Coccidioides, Histoplasma with?

Answer 13

Itraconazole

Question 14

Which Azole do you use to treat topical fungal infections?

Answer 14

Clotrimazole and miconazole

Question 15

Where are the toxicities/SE of the Azoles?

Answer 15

Testosterone synthesis inhibition (gynecomastia, esp with ketoconazole), liver dysfunction (inhibits CYP 450)

Question 16

Flucytosine Mech

Answer 16

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

Question 17

Clinical use of Flucytosine

Answer 17

Systemic fungal infection (esp. meningitis caused by Cryptococcus) in combination with Amphotercin B

Question 18

Toxicity of Flucytosine

Answer 18

Bone Marrow Suppression

Question 19

What are the Echinocandins?

Answer 19

Caspofungin, micafungin, anidulafungin

Question 20

What is the mechanism of the Echinocandins?

Answer 20

Inhibits cell wall synthesis by inhibiting synthesis of beta glucan

Question 21

What is the clinical use of Echinocandins?

Answer 21

Invasive Aspergillosis, Candida

Question 22

What is the toxicity of Echinocandins?

Answer 22

GI upset, flushing (by histamine release)

Question 23

Terbinafine mech

Answer 23

Inhibits the fungal enzyme squalene epoxidase

Question 24

Clinical use of Terbinafine

Answer 24

Dermatophytoses (especially onychomycosis - fungal infection of finger or toe nails). Tinea fungi

Question 25

Terbinafine Toxicity

Answer 25

GI upset, headaches, hepatotoxicty, taste disturbance

Question 26

Griseofulvin Mech

Answer 26

Interferes with microtubule function; disrupts mitosis. Deposits in keratin containing tissues (i.e nails)

Question 27

Clinical use of Griseofulvin

Answer 27

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

Question 28

Toxicity of Griseofulvin

Answer 28

Teratogenic, carcinogenic, confusion, headaches, increased P-450 and warfarin metabolism.