Mycoses, drugs used systemic

The drugs used in the treatment of subcutaneous and systemic mycoses are amphotericin B, flucytosine, and the new group of azoles, ketoconazole, fluconazole and itraconazole. 

Grant, S.M. Clissold, S.P. (1989) Itraconazole a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses. Drugs, 37, 310-344. 

Amphotericin B [am foe TER i sin] is a naturally occurring polyene macrolide antibiotic, produced by Streptomyces nodosus. In spite of its toxic potential, amphotericin B is the drug of choice used in the treatment of the systemic mycoses. It is sometimes used in combination with flucytosine so that lower (less toxic) levels of amphotericin are possible. 

Flucytosin i.v., 0. ind. systemic mycoses, given in combination with amphotericin B resistance when used as monotherapy bone marrow toxicity, nephrotoxicity, hepatotoxicity avoid other nephrotoxic drugs cytarabin as antagonist... 

Goa KL, BarradeU LB. Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients. Drugs 1995 50(4) 658-90. Erratum in Drugs 1996 51(3) 505. 

Hamycin, used for the treatment of 30 patients with proven vaginal moniliasis, produced cxires in 29 patients and was considered to be an outstanding drug for the treatment of this disease.29 in contrast to this its use in 10 cases of systemic mycoses resulted in improvement in only two cases.30 A question has been raised as to the possible identity, or at least close similarity of hamycin, trichomycin and candicidin. 

Classification and pharmacokinetics The azoles used for systemic mycoses include ke-toconazole, fluconazole, itraconazole, and voriconazole. Oral bioavailability is variable (normal gastric acidity is required). Hueonazole and voriconazole are more reliably absorbed via the oral route than the other azoles. The drugs are distributed to most body tissues, but with the exception of fluconazole, drug levels achieved in the CNS are low. Liver metabolism is responsible for the elimination of ketoconazole, itraconazole, and voriconazole. Fluconazole is eliminated by the kidneys, largely in unchanged form. 

Imidazoles arc wide-spectnim antifungal drugs to which resistance rarely develops. Except for ketoconazolc. the imidazoles are poorly absorbed orally. Clotrimazole, econii/ule and miconazole are widely used lopic-aliy in the Ireatment of dennaiophyle and Candida alhicam infections. Miconazole is used intravenously in systemic infections in patients who cannot tolerate amphotericin. It may cause nausea and vomiting, faintness and anaphylaxis. Ketoconazole is well absorbed orally, and has been used in Ihe crealment of local and systemic mycoses. Enthusiasm for ketoconazole has declined because it may cause hepatic necrosis and adrenal suppression. 

Any plans to make new therapeutics for Chagas disease need to bear in mind the characteristics of a drug that would allow it to succeed in clinical use. Essentially all the data in animal models and the clinical experience with humans indicate that long courses of treatment are required to produce cures. The situation is analogous to tuberculosis infection and systemic mycoses in which extended periods of drug pressure are necessary to kill off all the organisms. 

Clinical Experience - Intravenous administration of amphotericin B continues to be the major therapy for the treatment of systemic mycoses. Nebulization of amphotericin B was used to avoid some aspects of toxicity associated with intravenous use. Nebulization produced an aerosol with 8o-90 of the drug... 

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