Wk 2 Antifungal Meds

Question 1

Polyenes:

Amphoteracin B and Nystatin

Answer 1

Mechanism: bind ergosterol, create membrane holes –> fungicidal

Spectrum: systemic infections in immunocompromised pts

Adverse: nephrotoxicity ~70% pts, nystatin: topical Candida infection

Resistance: rare, decrease in membrane ergosterol

Distribution: long half-life, can cross blood-brain barrier

Question 2

Azoles:

Fluconazole, Itraconazole, Ketoconazole

Answer 2

Mechanism: inhibits fungal P450 (Erg111), decreasing ergosterol and increasing linosterol

Spectrum: varies by agent

Adverse: XX PREGNANCY XX, neurotoxicity, hepatotoxicity, hormone synthesis problems

Resistance: increased efflux, P450 binding changes

Distribution: increased absorption with acid

Question 3

Allylamines:

Terbinafine

Answer 3

Mechanism: inhibits squalene epoxidase, decreases ergosterol production, increases squalene

Spectrum: dermatophytes

Adverse: topical w/ CYP2D6 substrates

Resistance: CYP2D6 changes, increased efflux, decreased uptake

Question 4

Flucytosine

Answer 4

Mechanism: converted to 5-FU in fungi

Spectrum: yeast of Candida albicans and Crypotococcus

Adverse: bone marrow suppression

Resistance: changes in uptake or converting enzymes, often used with Amphoteracin B cotreatment to penetrate cells

Distribution: oral, penetrates CNS

Question 5

Griseofulvin

Answer 5

Mechanism: binds microtubules –> multinucleated cells –> fungistatic

Spectrum: dermatophytes

Adverse: XX PREGNANCY XX

Resistance: beta-tubulin changes

Distribution: increased uptake with lipid consumption

Question 6

Echinocandins:

Caspofungin

Answer 6

Mechanism: blocks beta-1,3-glucan polysaccharide synthesis. fungicidal-Candida, fungistatic-Aspergillis

Spectrum: Candida albicans, systemic

Adverse: rash, pain w/ injection

Resistance: beta-1,3-glucan synthase gene alteration

Distribution: IV, no CNS penetration w/ large MW