Antifungals

Question 1

Amphotericin B

Answer 1

Polyene macrolide

Pores are formed in the fungal cell membrane, allowing leakage of K+ and Mg+

Life-threatening invasive fungal infections; broad antifungal spectrum; (occasionally used with flucytosine in immunocompromised hosts)

Chronic: fall in renal function (may only be partially reversible); K+ Mg+ wasting; renal tubular acidosis Acute during IV infusion: fever/chillls; potential for hypotension; Lipid formulations result in better tolerability

Question 2

Nystatin

Answer 2

Polyene macrolide

Pores are formed in the fungal cell membrane, allowing leakage of K+ and Mg+

Topically (powder) against superficial fungal infections (candidiasis only)
No use against dermatophytes

Question 3

Fluconazole

Answer 3

Triazole / Cell membrane synthesis inhibitor

Inhibit ergosterol synthesis by inhibiting lanosterol demethylase

Candida infections; secondary treatment and prophylaxis of cryptococcal meningitis

Hepatotoxicity (rarely), GI side effects, inhibits CYP450 Clotrimazole = topical; fluconazole = systemic

Question 4

Voriconazole; Itraconazole

Answer 4

Triazole / Cell membrane synthesis inhibitor

Inhibit ergosterol synthesis by inhibiting lanosterol demethylase

Candida & Aspergillus infections

Hepatotoxicity (rarely), GI side effects, inhibits CYP450 Visual disturbances w/ voriconazole

Question 5

Posaconazole

Answer 5

Triazole / Cell membrane synthesis inhibitor

Inhibit ergosterol synthesis by inhibiting lanosterol demethylase

Candida, Fusarium, Mucorales infections

Hepatotoxicity (rarely), GI side effects, inhibits CYP450

Question 6

Efinazonazole (Jublia)

Answer 6

Azole / Cell membrane synthesis inhibitor

Inhibit ergosterol synthesis by inhibiting lanosterol demethylase

Candida; Tinea

Application site dermatitis, pain

Question 7

Tolnaftate; Terbinafine

Answer 7

Allylamine / Cell wall synthesis inhibitor

Inhibit ergosterol synthesis by inhibiting squalene epoxidase

Topical dermatophytes (limited utility against candida)

Hepatotoxicity (rarely)
Low side effect profile
Terbinafine effective against onychomycoses; tolnaftate: oral only; weak agent

Question 8

Capsofungin; Micafungin; Anidulafungin

Answer 8

Echinocandin / Cell wall synthesis inhibitor

Inhibit synthesis of Beta(1,3)-D-glucan, an essential component of the fungal cell wall

Life-threatening fungal infections unresponsive to older agents (especially candida, aspergillus)

Low side effect profile , Expensive; only available as IV formulation

Question 9

Flucytosine

Answer 9

Nucleic acid synthesis inhibitor

Prodrug converted by fungal enzyme to analog inhibitor of pyrimidine nucleotide synthesis

Used in combo with amphotericin B in life threatening fungal infections in immunocompromised patients.

Bone marrow toxicity; Liver dysfunction possible