Polyenes
Examples
- Amphotericin
- Nystatin
Indications
- Amphotericin is used in systemic fungal infections; nystatin is used topically for local fungal infections
- Amphotericin is active against most fungi and yeasts, and is the gold standard for treating disseminated infections caused by several organisms including Aspergillus and Candida
- Excellent action against Cryptococcus neoformans
- Good action against Candida albicans, Aspergillus fumigatus, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatides
Contraindications
Contraindications
- Hypersensitivity
- Hepatic impairment
- Renal impairment
- Pregnancy and breast-feeding
Mechanism
These drugs act on the fungal cell membrane, where they interfere with permeability and with transport functions. The primary action is its ability to form large pores in the membrane. The hydrophilic core of polyene antifungals form a transmembrane ion channel, resulting in ion balance disturbances, including the loss of intracellular K+.
Administration
Nystatin is used topically, and can be used by mouth as it is very poorly orally absorbed. It is highly toxic if given systemically. Amphotericin is given intravenously, and is also toxic. Lipid formulations of amphotericin allow larger doses to be given safely.
Different brands of amphotericin have different dosing recommendations, therefore the brand of amphotericin to be used should be specified when prescribing.
Adverse Reactions
- Anaphylactic and anaphylactoid reactions are common, so a test dose is recomnmended
- Fever, nausea and vomiting are also common
- Rash can be severe
- Rapid infusion can precipitate arrhythmias
- Nephrotoxicity is seen in almost all patients
- Other important problems include: seizures, neuropathies, hearing loss, hepatotoxicity and blood disorders
Interactions
- Cardiac glycosides - cardiac toxicity increased
- Ciclosporin and other cytotoxics - nephrotoxicity
- Corticosteroids - risk of hypokalaemia
Education
Close monitoring of intravenous treatment is needed.
Pharmacokinetics
Amphotericin is poorly absorbed when given orally and is hence administered by slow intravenous infusion. It is a highly protein-bound molecule and as such penetrates tissues and membranes (such as the blood-brain barrier) poorly. It is found in inflammatory exudates and may pass the blood brain barrier more readily when meninges are inflamed. It is excreted, very slowly, by the kidney. Residues may be found in the urine over 2 months post treatment.
