5. Antifungals

Question 1

Amphotericin B - MOA

Answer 1

Binds ergosterol (fungal specific) and forms membrane pores that allow leakage of electrolytes.

“AmphoTERicin TEARS holes in the fungal membrane”

Question 2

Amphotericin B - Clinical Use

Answer 2

SERIOUS, SYSTEMIC MYCOSES (Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor)

• Administer intrathecally for fungal meningitis. With or without Flucytosine for Cryptococcal meningitis
• Supplement K and Mg because of altered renal tubule permeability

Question 3

Amphotericin B - Toxicities

Answer 3

Fever/Chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (“amphoterrible”)

• Hydration reduces nephrotoxicity
• Liposomal Amphotericin reduces toxicity.

Question 4

Nystatin - MOA

Answer 4

Binds ergosterol (fungal specific) and forms membrane pores that allow leakage of electrolytes.
- TOPICAL only - too toxic for systemic use

Question 5

Nystatin - Clinical Use

Answer 5

Swish and swallow for oral candidiasis - thrush

- Topical for diaper rash or vaginal candidiasis

Question 6

Azoles - Available Drugs

Answer 6

Fluconazole
Ketoconazole
Clotrimazole
Miconazole
Itraconazole
Voriconazole

Question 7

Azoles (Fluconazole, Ketoconazole, …) - MOA

Answer 7

Inhibit fungal sterol synthesis by inhibiting the P450 enzyme that converts lanosterol to ergosterol.

Question 8

Azoles (Fluconazole, Ketoconazole, …) - Clinical Use

Answer 8

Local of less serioud systemic mycoses

• Fluconazole for CRYPTOCOCCAL MENINGITIS IN AIDs PATIENTS.
• Fluconazole for all types of CANDIDAL INFECTIONS
• Ketoconazole for Blastomyces, Coccidioides, Histoplasma, Candida albicans.
• Ketoconazole also for hypercortisolism
• Clotrimazole and Miconazole for topical fungal infections

Question 9

Azoles (Fluconazole, Ketoconazole, …) - Toxicities

Answer 9

Hormone synthesis inhibition - Gynecomastia

• Liver dysfunction - P450 inhibition
• Fever, chills

Question 10

Flucytosine (5-Fluorocytosine) - MOA

Answer 10

Inhibit DNA synthesis by conversion to 5-fluorouracil by cytosine deaminase.

Question 11

Flucytosine (5-Fluorocytosine) - Clinical Use

Answer 11

In combination with Amphotericin B for Systemic fungal infections especially CRYPTOCOCCUS

Question 12

Flucytosine (5-Fluorocytosine) - Toxicities

Answer 12

Nausea, vomiting, diarrhea, bone marrow suppression

Question 13

Caspofungin - MOA

Answer 13

Inhibit cell wall synthesis by inhibiting synthesis of B-glucan

Question 14

Caspofungin - Clinical Use

Answer 14

INVASIVE ASPERGILLOSIS

Candida

Question 15

Caspofungin - Toxicities

Answer 15

GI upset, flushing

Question 16

Terbinafine - MOA

Answer 16

Inhibit fungal enzyme squalene epoxidase

Question 17

Terbinafine - Clinical Use

Answer 17

Dermatophytoses especially ONCHOMYCOSIS (fungal infection of the finger and toe nails)

Question 18

Terbinafine - Toxicities

Answer 18

Abnormal LFT’s

- Visual disturbances

Question 19

Griseofulvan - MOA

Answer 19

Interfere with microtubule function - disrupt mitosis.

- Deposits in keratin containing tissues (nails)

Question 20

Griseofulvan - Clinical Use

Answer 20

Oral treatment of superficial infections

- Inhibits growth of DERMATOPHYTES (tinea, ringworm)

Question 21

Griseofulvan - Toxicities

Answer 21

Teratogenic, Carcinogenic

• Confusion, headache
• Increases P450 activity and Warfarin metabolism