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Fungal infections and their management
1Health Science Center, University of Texas, San Antonio.
Abstract:
The first oral agents for treatment of mycoses included potassium iodide, griseofulvin and flucytosine. While each is still used in specific indications, the advent of ketoconazole in the late 1980s radically expanded the spectrum and efficacy of oral antifungals. Ketoconazole was the first drug sufficiently potent and benign to permit use for both superficial and deep fungal infections. Ketoconazole quickly proved highly effective in many systemic and cutaneous infections, but it was soon appreciated that high doses caused impairment of testosterone and ultimately cortisol synthesis. Dose-dependent nausea and vomiting also became apparent, as did the necessity for very high doses for treatment of fungal meningitis. Hepatic cellular toxicity was also noticed, particularly after prolonged treatment at high doses. Just as these limitations became apparent, Janssen, Pfizer and, most recently, Schering brought forth the triazole antifungals. These differ markedly in pharmacokinetics and fungal spectrum, requiring careful consideration of the appropriate drug. In addition to the above, terbinafine has been recently developed for dermatophytes, particularly refractory onychomycoses.
Insights
Oral antifungal medications have evolved significantly, from early agents like griseofulvin to more potent options such as ketoconazole. Newer triazole antifungals and terbinafine offer improved efficacy and spectrum for various fungal infections.
Area of Science:
- Medical Mycology
- Pharmacology
Background:
- Early oral antifungals like potassium iodide, griseofulvin, and flucytosine had limited applications.
- Ketoconazole, introduced in the late 1980s, marked a breakthrough, offering broad efficacy for superficial and deep fungal infections.
Purpose of the Study:
- To review the evolution and characteristics of oral antifungal agents.
- To discuss the efficacy, limitations, and therapeutic considerations of key oral antifungals.
Main Methods:
- Historical review of oral antifungal drug development.
- Analysis of pharmacokinetic and pharmacodynamic properties of key agents.
- Summary of clinical applications and adverse effects.
Main Results:
- Ketoconazole demonstrated broad efficacy but had dose-limiting toxicities including hormonal impairment and hepatotoxicity.
- Triazole antifungals emerged with distinct pharmacokinetic profiles and fungal spectra.
- Terbinafine was developed specifically for dermatophyte infections, especially onychomycosis.
Conclusions:
- The development of oral antifungals has progressed from limited agents to broad-spectrum drugs like ketoconazole and newer triazoles.
- Understanding the specific properties of each agent is crucial for effective treatment of diverse fungal infections.
- Ongoing advancements continue to improve therapeutic options for mycoses.