Polyene antifungal drug

Antifungal drugs are classified according to their mode of action and/or their chemical class. Four chemical classes have mainly contributed to the actual armentory of antifungal drugs the broadest class is the one of azoles (imidazoles and triazoles), followed by polyenes, allylamines and morpholines. Some individual compounds are used in dermatology. 

Amphotericin B (Fungizone), a polyene antifungal drug produced by the actinomycete Streptomyces nodosus, consists of a large ring structure with both hydrophilic... 

Nystatin (Mycostatin) is a polyene antifungal drug with a ring structure similar to that of amphotericin B and a mechanism of action identical to that of amphotericin B. Too toxic for systemic use, nystatin is limited to the topical treatment of superficial infections caused by C albicans. Infections commonly treated by this drug include oral candidiasis (thrush), mild esophageal candidiasis, and vaginitis. 

The best-known polyene antifungal drug is Amphotericin B, whose structure is shown below. 

Sensitisation to modern antifungal drugs is not a common experience. It has been reported, and confirmed by adequately controlled patch tests, to tolnaftate (Gellin et al. 1972 Emmett and Marks 1973), to the polyene antibiotic, pecilocin (SuNDERARAJAN 1970 Groen et al. 1973 Norgaard 1977), chlordantoin (Epstein 1966), haloprogin (Rudolph 1975 Sturde 1975 Hollander 1977) and to fluonilid (Van Hecke 1969), but cases are sufficiently unusual for even individual case reports to be noted (Fig. 4). 

Natamycin is the only polyene antifungal drug authorised for food animal use in the EU (Table 11.1) and in view of its low percutaneous and gastrointestinal absorption, its use on individual cattle or horses and its low toxicity, it was considered that no maximum residue limit (MRL) was required on public health grounds. ... 

Hoeprich and Huston [117] assessed the stability of miconazole and three other antifungal agents under conditions encountered in bioassay and susceptibility testing in vitro. Although the amphotericins were labile as compared with other drugs, tests should be reliable with all four drugs in view of the rapid action of the polyenes and the relatively slow action of miconazole and 5-fluorocytosines. 

There are relatively few chemotherapeutic drugs which cause permeability increases in membranes such as the antifungal polyenes and the antibacterial circular oligopeptides of the tyrocidin, gramicidin and polymyxin families. Most of these are too toxic for systemic use but polymyxins have been given systemically in severe Pseudomonas infections with an attending risk of renal toxicity. 

Amphotericin B - Observations on the immunostimulant properties of the clinically used antifungal polyene antibiotic amphotericin B (AmB) and its methylester (AME) were extended. In mice, the drugs augmented antibody formation to TNP-HSA with pronounced enhancement of secondary IgG responses,... 

The many publications in this area during 1966 have covered both the elaboration and verification of the usefulness of previously known drugs and the announcement of new compounds with potentially interesting activity. Considerable effort has also been given to the study of the mode of action of various antifungal antibiotics. The material in this chapter is divided primarily into sections on polyene antibiotics, nonpolyene antibiotics and synthetic compoxinds. 

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