Antifungal drugs amphotericin

DRUGS TO TREAT INFECTIONS ANTIFUNGAL DRUGS Amphotericin... 

Antifungal drugs are used to treat superficial and deep fungal infections. The antifungal drugs specifically discussed in this chapter are amphotericin B (Fungizone), flucona-... 

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 polyketides are a large family of bio synthetically related NPs, some of which have very great pharmaceutical value (polyketide sales total about 10 billion annually, see also Chapter 7). Some antibiotics (erythromycin, monensin, rifamycin), immunosuppressants (rapamycin), antifungal substances (amphotericin), antiparasitic (aver-mectin) and anticancer drugs (doxorubicin) are polyketides. The term polyketide refers to the fact that the basic carbon skeleton is not a simple hydrocarbon chain as in the case of fatty acids but is a series of linked keto groups in sequence (Figure 3.6). The first phase of this pathway, the generation of carbon skeleton diversification. 

SYSTEMIC ANTIFUNGAL DRUGS FOR SYSTEMIC INFECTIONS AMPHOTERICIN ... 

This important antifungal drug (see Chapter 48) is an alternative therapy for visceral leishmaniasis, especially in parts of India with high-level resistance to sodium stibogluconate. Liposomal amphotericin has shown excellent efficacy at a dosage of 3 mg/kg/d intravenously on days 1-5, 14, and 21. Nonliposomal amphotericin (1 mg/kg intravenously every other day for 30 days) is much less expensive, also efficacious, and widely used in India. Amphotericin is also used for cutaneous leishmaniasis in some areas. The use of amphotericin, and especially liposomal preparations, is limited in developing countries by difficulty of administration, cost, and toxicity. 

Yu et al. (1998) used amphotericin B (AmB), an antifungal drug, as a model to study the release pro-Lle of polyethylene oxide)-block-poly(benzyl-aspartate) (FISSBLA) block copolymer micelles. 

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

Amphotericin B is produced by a strain of bacteria, Streptomyces nodosus. Please refer to the general pharmacology section for antifungal drugs. 

Comparisons of amphotericin with other antifungal drugs... 

Nystatin was discovered in 1950 and exhibits the same mode of action as amphotericin B but tends to be of lower solubility, which has restricted its use to the treatment of topical infections. While nystatin was effective for the treatment of conditions such as oral and vaginal candidosis its use has been overtaken by the introduction of azole antifungal drugs. 

Hope and coworkers [91], in studying combination therapy of antifungal drugs in the treatment of invasive candidiasis, assessed pharmacodynamic interactions of amphotericin B deoxycholate and 5-fluorocytosine. The interaction model they used was based on the Greco model of drug interaction [92] represented by the equation... 

Amphotericin B remains the antifungal drug of choice for most systemic infections, but dose-dependent nephrotoxicity occurs to varying degrees in many patients. Toxicity is seen initially with cumulative doses as low as 300 to 400 mg, and reaches an incidence of 80% when cumulative doses approach 4 g. Several liposomal amphotericin B formulations are now available. Although numerous studies demonstrate lower rates of nephrotoxicity with hposomal formulations compared to conventional amphotericin B, it is difficult to compare rates of toxicity between products and studies due to varying study populations eiuoUed, different doses administered, and inconsistent definitions of nephrotoxicity and methods of assessment. ... 

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