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Chapter 22 : Antifungals: Drug Class, Mechanisms of Action, Pharmacokinetics/Pharmacodynamics, Drug-Drug Interactions, Toxicity, and Clinical Use

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Antifungals: Drug Class, Mechanisms of Action, Pharmacokinetics/Pharmacodynamics, Drug-Drug Interactions, Toxicity, and Clinical Use, Page 1 of 2

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Abstract:

Antifungal therapeutic outcomes have been historically suboptimal, in part, due to a relatively small number of safe and effective antifungal drugs. There are many important characteristics of antifungal drugs to consider in treatment of invasive fungal infection. Among these traits, spectrum of activity, pharmacokinetics, pharmacodynamics, potential drug-drug interactions, and toxicities are the most critical. This chapter focuses on these antifungal traits for available systemic agents for treatment of infection. The main toxicities include renal damage, electrolyte abnormalities from renal toxicity, hepato-toxicity, and infusion-related reactions. The majority of the drug-drug interactions are related to potentiation of the electrolyte disturbances and renal dysfunction typical of amphotericin B. For example, the risk of renal toxicity is increased if amphotericin B is used concomitantly with the organ transplant immuno-suppressants cyclosporine and tacrolimus. In addition, lipid-based amphotericin B formulations are preferred for treatment of pregnant patients due to gestational toxicity with the triazole drug class. Studies have found the primary toxicity of flucytosine, bone marrow toxicity, to be associated with high peak concentrations. The fact that the pharmacodynamic drivers of success and toxicity are different provides an opportunity to design dosing strategies to both optimize treatment efficacy and reduce toxicity. The major toxicities of flucytosine include bone marrow suppression and hepato-toxicity. The major route of elimination for echinocandins is non-enzymatic degradation to inactive molecules which are excreted primarily in the bile.

Citation: Nett J, Andes D. 2012. Antifungals: Drug Class, Mechanisms of Action, Pharmacokinetics/Pharmacodynamics, Drug-Drug Interactions, Toxicity, and Clinical Use, p 345-371. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch22

Key Concept Ranking

Fungal Infections
0.80401856
Antifungal Agents
0.8003516
Antifungal Drugs
0.58657146
Central Nervous System Diseases
0.5115577
Systemic Fungal Infections
0.43606475
0.80401856
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Chemical structures of systemically available antifungal agents. doi:10.1128/9781555817176.ch22.f1a

Citation: Nett J, Andes D. 2012. Antifungals: Drug Class, Mechanisms of Action, Pharmacokinetics/Pharmacodynamics, Drug-Drug Interactions, Toxicity, and Clinical Use, p 345-371. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch22
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Image of FIGURE 1b
FIGURE 1b

Chemical structures of systemically available antifungal agents. doi:10.1128/9781555817176.ch22.f1b

Citation: Nett J, Andes D. 2012. Antifungals: Drug Class, Mechanisms of Action, Pharmacokinetics/Pharmacodynamics, Drug-Drug Interactions, Toxicity, and Clinical Use, p 345-371. In Calderone R, Clancy C (ed), and Candidiasis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817176.ch22
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