Amphotericin B

Mechanism of action: binds to sterols present in the plasma membrane

more selective for ergosterol = major fungal sterol

forms cytotoxic pores

broadest spectrum of any antifungal

Absorption: very poor

given slowly IV as liposome suspension, or used topically

given orally for GI fungi, but as such is really acting ‘topically’

Uses:

initial drug of choice for life-threatening systemic infections

Invasive Aspergillus (30% survival); used with itraconazole

Cryptococcal meningitis; used with flucytosine (alternative: fluconazole)

Rapidly developing Histoplasmosis

some limited use for cutaneous (dermatophytic) infections

or mucocutaneous infections

Adverse effects: fairly toxic [some binding to mammalian membranes; effects reduced via use of liposome delivery]

- fever and chills; vomiting; muscle spasms; modest hypotension (nearly 100% but treatable; small test dose usually given to assess reactions)

- renal impairment (near 80%)

- hypokalemia (= reduced serum K)

Nystatin

Mechanism of action: same as for Amphotericin B

Absorption: extremely poor

Uses: much too toxic for systemic (parental) use

used only topically

local (dermal), oropharyngeal, GI and vaginal candidiasis only

[other than its nasty, bitter taste, adverse effects are uncommon]

Category: Pharmacology Notes