Antifungal Agents

Question 1

Drugs used for systemic fungal infections

Answer 1

• Amphotericin B
• Flucytosine
• Ketoconazole, Fluconazole, Itraconazole, Variconazole
• Caspofungin

Question 2

Amphotericin B: Mechanism of action

Answer 2

• Polyene antibiotic
• Administered IV
• Act on the permeability and transport properties of fungal membranes
• Have both hydrophilic and lipophilic characteristics
• Bind to ergosterol, and cause the formation of artificial pores

Question 3

Amphotericin B: Clinical

Answer 3

• One of the most important drug used against systemic mycoses
• Often used for initial induction regimens before follow-up treatment with an azole
• Has the widest antifungal action
• Drug of choice against Aspergillus, Blastomyces, Candida albicans, Cryptococcus, Histoplasma, and Mucor

Question 4

Flucytosine (5-FC)

Answer 4

• Pyrmidine antimetabolite
• Dose dependent renal impairment
• Accumulate in fungal cells –> converted by cytosine deaminase to 5-FU –> inhibitor of thymidylate synthase
• Narrow antifungal spectrum: limited to treatment, in combination with Amphotericin B or Fluconazole, of Cryptococcus neoformans

Question 5

Azoles: Mechanism of Action

Answer 5

• Interfere with fungal cell membrane permeability
• Inhibit synthesis of ergosterol, at the step of 14α-demethylation of lanosterol (catalyzed by a cytochrome P450 isozyme

Question 6

Ketoconazole

Answer 6

• Rarely used for systemic mycoses because of its adverse effects
• Used for chronic mucocutaneous candidiasis and, when given orally, against dermatophytes

Question 7

Fluconazole

Answer 7

• Drug of choice in esophageal and oropharyngeal candidiasis and for most infection caused by Coccidioides
• Drug of choice for initial and secondary prophylaxis against cryptococcal meningitis
• Alternative drug of choice (with Amphotericin B) in treatment of active disease due to Cryptococcus neoformans

Question 8

Itraconazole

Answer 8

• Drug of choice for systemic infections cause by Blastomyces and Sporothrix and for subcutaneous chromoblastomycosis
• Alternative drug in treatment against Aspergillus, Coccidioides, Cryptococcus, and Histoplasma
• Used against dermatophytes, especially onychomycosis

Question 9

Voriconazole

Answer 9

• Codrug of choice for treatment of invasive apergillosis
• Alternative drug in candidemia
• In AIDS patients has been used in the treatment of candidial esophagitis and stomatitis

Question 10

Caspofungin

Answer 10

• Echinocandin
• Used IV
• Inhibit the synthesis of β(1-2)glycan, a critical component of fungal cell walls
• Approved only for use against invasive aspergillosis

Question 11

Griseofulvin

Answer 11

• Systemic drug used for superficial fungal infections
• Distribute to stratum corneum, binds to keratin
• Interferes with microtubules function in dermatophytes
• May inhibit the synthesis and polymerization of nucleic acids
• Used against dermatophytes of skin and hair

Question 12

Terbinafine

Answer 12

• Systemic drug used for superficial fungal infections
• Fungicidal
• Inhibits the fungal enzyme, squalene epoxidase –> accumulation of toxic level of squalene –> interfere with ergosterol synthesis
• Effective against onychomycosis

Question 13

Nystatin

Answer 13

• Topical drug
• Polyene antibiotic
• Disrupts fungal membranes by binding to ergosterol
• Used to suppress local Candida infections