,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,单击此处编辑母版标题样式,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,Adverse Effects:,Infusion-Related Toxicity:,fever,chills,muscle spasms,vomiting,headache,hypotension.,Slower Toxicity:,Renal toxicity,K,+,Mg,2+,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.,Azoles,Synthetic compounds.,Classification:,according to the number of nitrogen atoms in the five-membered azole ring,Imidazoles:,Ketoconazole,Miconazole,Econazole,Clotrimazole,Bifonazole,Triazoles:,Itraconazole,Fluconazol,Vorionazole,systemic treatment,Mechanism of Action,Reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes.,Greater affinity for funfal,than for human cytochrome P450 enzymes.,Imidazoles exhibit a lesser degree of specificity than the triazoles,accounting for their higher incidence of drug interactions and side effects.,Miconazole,Econazole,Clotrimazole,Bioavailability is low by taking orally.,Used topically.,Itraconazole,Its absorption is increased by food and by low gastric pH.,Treatment of,dermatophytoses,(皮真菌病)and,onychomycosis,(甲真菌病).,The only agent with significant activity against,aspergillus,(曲霉菌)species.,Fluconazol,Water solubility and good cerebrospinal fluid penetration.,The,widest therapeutic index,(治疗指数)of the azoles.,Treatment and secondary prophylaxis(预防)of,cryptococcal meningitis（,隐球菌脑膜炎,）,.,Acrylamide,Include,Naftifine,and,Terbinafine,.,non-competitive and reversible,inhibitor,of,Squalene epoxidase,.,Terbinafine,is synthetic,oral formulation.,Fungicidal（杀菌剂）,Treatment of dermatophytoses,especially,onychomycosis,more effective than griseofulvin or itraconazole.,Pyramine,Flucytosine（5-FC）is a,water-soluble,pyrimidine analog,.,Its spectrum of action is much,narrower,than that of,amphotericin B,.,Poorly protein-bound,and,penetrates well,into all body fluid aompartments,including the,cerebrospinal fluid.,Mechanism,5-FC,(taken up by fungal cells via the enzyme cytosine permease),5-FU,F-dUMP,and,FUTP,inhibit DNA and RNA synthesis,respectively.,Synergy(协同)with amphotericin B.,Spectrum of action:,Cryptococcus neoformans,some candida species,and the,dematiaceous molds,that cause chromoblastomycosis.,Not used as a single agent,because of its demonstrated,synergy,with other agents and to avoid the development of secondary,resistance,.,Adverse effects:,result from metabolism to fluorouracil(,5-FU,),Bone marrow toxicity,with anemia,leukopenia,and thrombocytopenia,