Antifungals

Question 1

What are the 4 classes of antifungals that inhibit cell wall synthesis? Which are topical and which systemic?

Answer 1

Imidazoles (topical- too toxic for systemic use)
Allylamines (systemic & topical)
Triazoles (systemic)
Fungins (systemic)

Question 2

Name 3 topical antifungals. Mechanism?Spectrum?

Answer 2

Clotrimazole (imidazole) - broad spectrum: candida & dermatophytes
Tolnaftate (allylamine) - narrow spectrum: only dermatophytes
–> both inhibit ergosterol synthesis

Nyastatin (polyene) - candida (powder, swish&swallow)
–> form pores in fungal membrane

Question 3

Name 5 systemic antifungals

Answer 3

Fluconazole (triazole)
Terbinafine (allylamine)
Caspofungin (fungin)
Amphotericin B (polyene)
Flucytosine

Question 4

What drug would be used for onychomycoses?

Answer 4

Terbinafine (allylamine)

–> dermatophyte that needs to be treated systemically for 3-6mos

Question 5

What is the mechanism and use of Caspofungin?

Answer 5

MECHANISM: Inhibits glucan synthase complex –> cell wall synthesis inhibitor
USE: Life-threatening fungal infections unresponsive to older agents (especially candida, aspergillus); usually in HIV pts

Question 6

What 2 agents are used in combo for severe candidal and cryptococcal infections in immunocompromised patients?

Answer 6

Amphotericin B (polyene)
Flucytosine

Question 7

What agent is used for Thrush? Spectrum of this agent?

Answer 7

Nystatin

• swish&swallow (No absorption in GI)
• only useful against candida

Question 8

What is the mechanism, use and side effects of Amphotericin B?

Answer 8

MECH: Pores are formed in the fungal cell membrane, allowing leakage of K+ and Mg+
USE: wide fungicidal spectrum; ONLY used in severe, invasive infections
SE:
-Acute during IV infusion: fever/chillls; potential for hypotension
-Chronic: fall in renal function (may only be partially reversible); K+ Mg+ wasting; renal tubular acidosis; normocytic anemia in bone marrow

Question 9

What is the mechinism, use and side effects of Flucytosine?

Answer 9

MECHANISM: Prodrug converted by fungal enzyme to analog inhibitor of pyrimidine nucleotide synthesis
USE: Used in combo with amphotericin B in life threatening fungal infections in immunocompromised patients
SE: Sloughing of GI mucosa; centrolobular hepatitis; bone marrow cytopenias