【医学课件】 Antifungal Agents.pptVIP

Antifungal Agents Fen-Fei Gao Overview Fungal infections classification: Superficial infections: Ringworm (tinea) → skin and mucous membrane. Incidence rate is high. Systemic infections: Candida albicans → opportunist infections. Fatality rate is high. Antifungal agents classification: Antibiotics: Amphotericin B; Azole: Ketoconazole; Allylamine: Terbinafine; Pyrimidine: Flucytosine. Antibiotic Antifungal Drugs Polyenes: Amphotericin B, Nystatin Non-polyenes: Griseofulvin Amphotericin B Produced by Streptomyces nodosus. Amphoteric polyene macrolide. Pharmacological Effect: broad-spectrum Mechanism: binds to ergosterol in fungi (cholesterol in humans and bacteria) to form pores Pharmacokinetics: Poorly absorbed from the gastrointestinal tract. More than 90% bound by serum proteins. Metabolized in liver, excreted slowly in the urine. Adverse Effects: Infusion-Related Toxicity: fever, chills, muscle spasms, vomiting, headache, hypotension. Slower Toxicity: Renal toxicity K+↓, Mg2+↓ Anemia: erythropoietin (促红细胞生成素)↓ Abnormalities of liver function Neurologic sequela Announcements: Administration in advance of NSAIDs and Antihistamine drug, Glucocorticoid Periodic Monitoring Liposomal Amphotericin B Lipid preparations reduce toxicity without sacrificing efficacy. Lipid formulations distributes mostly in reticular endothelial tissue (liver, spleen, lung), but less in kidney. Nysfungin Like Amphotericin B and has same mechanism of action. Too toxic for parenteral administration, and is only used topically (局部). Not absorbed from skin, mucous membranes, or the gastrointestinal tract, so little significant toxicity. Ketoconazole The first oral azole introduced into clinical use.