Polyenes

Polyenes

The polyenes include amphotericin B and nystatin. Ampho-tericin B’s potency has made it the most widely used antimycotic drug for severe systemic fungal infections. It’s available in several forms, including lipid-based preparations that may decrease renal or systemic toxicity. Nystatin is used only topically or orally to treat local fungal infections because it’s extremely toxic when ad-ministered parenterally.

Pharmacokinetics

After I.V. administration, amphotericin B is distributed throughout the body and excreted by the kidneys. Its metabolism isn’t well de-fined.

Oral nystatin undergoes little or no absorption, distribution, or metabolism. It’s excreted unchanged in stool. Topical nystatin isn’t absorbed through the skin or mucous membranes.

Pharmacodynamics

Amphotericin B works by binding to sterol (a lipid) in the fungal cell membrane, altering cell permeability (ability to allow a substance to pass through) and allowing intracellular components to leak out.

A license to kill

Amphotericin B usually acts as a fungistatic drug (inhibiting fun-gal growth and multiplication), but can become fungicidal (de-stroying fungi) if it reaches high concentrations in the fungi.

Nystatin binds to sterols in fungal cell membranes and alters the permeability of the membranes, leading to loss of cell compo-nents. Nystatin can act as a fungicidal or fungistatic drug, depend-ing on the organism present.

Pharmacotherapeutics

Amphotericin B usually is administered to treat severe systemic fungal infections and meningitis caused by fungi sensitive to the drug. It’s never used for noninvasive forms of fungal disease be-cause it’s highly toxic. It’s usually the drug of choice for severe in-fections caused by Candida, Paracoccidioides brasiliensis, Blas-tomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, and Sporothrix schenckii. It’s also effective against As-pergillus fumigatus, Microsporum audouinii, Rhizopus, Candi-da glabrata, Trichophyton, and Rhodotorula.

Last-ditch effort

Because amphotericin B is highly toxic, its use is limited to the pa-tient who has a definitive diagnosis of life-threatening infection and is under close medical supervision.

Topical concerns

Nystatin is used primarily to treat candidal skin infections. Differ-ent forms of nystatin are available for treating different types of candidal infections. Topical nystatin is used to treat candidal skin or mucous membrane infections, such as oral thrush, diaper rash, vaginal and vulvar candidiasis, and candidiasis between skin folds.

Oral history

Oral nystatin is used to treat GI infections.

Drug interactions

Nystatin doesn’t interact significantly with other drugs, but am-photericin B may have significant interactions with many drugs.

·                 Because of the synergistic effects between flucytosine and am-photericin B, these two drugs commonly are combined in therapy for candidal or cryptococcal infections, especially for cryptococ-cal meningitis.

·                 The risk of kidney toxicity increases when amphotericin B is taken with aminoglycosides, cyclosporine, or acyclovir.

·                Corticosteroids, extended-spectrum penicillins, and digoxin may worsen the hypokalemia (low blood potassium levels) pro-duced by amphotericin B, possibly leading to heart problems. Moreover, the risk of digoxin toxicity is increased.

·                 Amphotericin B plus nondepolarizing skeletal muscle relaxants (such as pancuronium bromide) increase muscle relaxation.

·                 Electrolyte solutions may inactivate amphotericin B when dilut-ed in the same solution. Amphotericin B preparations must be mixed with dextrose 5% in water; they can’t be mixed with saline solution.

·                 Magnesium and potassium levels and kidney function must be monitored frequently in patients receiving amphotericin. (See Ad-verse reactions to amphotericin B and Adverse reactions to nys-tatin.)