Anti-Fungal Drugs

Question 1

Drugs Targeting Ergosterol

Answer 1

Polyenes
Azoles
Allylamines

Question 2

Amphotericin B

Answer 2

Polyene
Produced by Streptomyces nodosus
Drug of Choice
Binds ergosterol

Question 3

Nystatin

Answer 3

Polyene
Binds ergosterol
Used topically
Oral and esophageal fungal infections
Vaginal candidiasis

Question 4

Azoles

Answer 4

Synthesized
Inhibit cytochrome P450 14-a demethylase (P45014DM)
In sterol biosynthesis path of lanosterol to ergosterol
2 types: imidazoles and triazoles

Question 5

Imidazoles

Answer 5

Azoles
Ketoconazole: DOC for chronic mucocutaneous candidiasis
Miconazole/Clotrimazole: topical fungal infections

Question 6

Triazoles

Answer 6

Azoles
less toxic than imidazoles
Flucanozole: cutaneous and vaginal candidiasis, second line agent behind amphotericin B for systemic candidiasis and cryptococcal meningitis
Itraconazole: broad-spectrum anti-fungal, taken orally and less side effects than ketoconazole and amphotericin B
Posaconazole: consistent activity against majority of zygomycetes

Question 7

Allylamines

Answer 7

Inhibit squalene epoxicas- essential in ergosterol synthesis
(squalene to lanosterol to ergosterol)
Naftifine and Terbinafine (topical and oral)- treat dermatophyte infections

Question 8

Drugs Targeting Cell Wall Synthesis

Answer 8

Echinocandins (Capsofungin approved)
Inhibit B- 1,3 glucan synthesis (component of cell wall)
Treat candida infections and invasive aspergillosis
Not effective against cryptococcus infections

Question 9

Drugs Targeting Cell Division

Answer 9

Griseofulvin
Produced by Penicillin- species
Orally, becomes concentrated into dead keratinized layers where fungal growth is inhibited
Static, rather than cidal
Active against ringworm of skin, nails or hair due to Trichophyton, Epidermophyton, and Microsporum

Question 10

Drugs Targeting Nucleic Acid Synthesis

Answer 10

Flucytosine
Inhibits fungal protein synthesis- Uracil replaced with 5-flurouracil in fungal RNA; inhibits thymidylate synthetase via 5-flurodeoxyuridine monophosphate interfering with fungal DNA synthesis
Resistance is common
Effective against candidiasis and cryptococcosis but not molds