《（表皮癣菌）课件》由会员分享，可在线阅读，更多相关《（表皮癣菌）课件（35页珍藏版）》请在金锄头文库上搜索。
1、Chapter 43 Antifungal and Antiviral Drugs,Antifungal drugs,Fungal infection Superficial infection Systemic infection Antifungal drugs Antifungal antibiotics Azole: imidazole and triazole Others: terbinafine and flucytosine,Antifungal antibiotics,Griseofuvin Amphotericin B Nystatin,Griseofulvin,Antif
2、ungal activity inihibit the growth of dermatophytes include epidermophyton（表皮癣菌）, microsporum（小孢子菌） and trichophyton（发癣菌属） no effect on bacteria and systemic infections of fungi Mechanism of action interfere with fungal nucleic acid synthesis,Griseofulvin,Clinical useit is only used in the systemic
3、treatment of dermatophotosis include skin, hair and nails Adverse effectsNausea, vomiting ,headache Allergic reaction: fever, skin rash and leukopenia Teratogenesis,Amphotericin B,Antifungal activity Has the broadest spectrum of antifungal action Active against candida albicans, cryptococcus neoform
4、ans, histoplasma capsulatum etc,Amphotericin B,Mechanism of action Bind to ergosterol on fungal cell membrane and alter the permeability of the cell by forming amphotericin B-associated pores in the cell membrane, allow the leakage of intra-cellular ions(K+) and molecules leading to cell death,Ampho
5、tericin B,Clinical uses Drug of choice for nearly all life-threatening mycotic infections include severe fungal pneumonia, crypotoccal meningitis or sepsis syndrome,Amphotericin B,Adverse reactions Infusion-related toxicity: fever, chills, muscle spasm, headache, hypotension Renal damage: azotemia,
6、K+ ,Mg2+ wasting Others: Liver damage, arrthymia, anemia,New preparation,Liposomal amphotericin B(两性霉素B脂质体） Amphotericin B lipid complex（两性霉素B脂质复合体） Amphotericin B colloidal dispersion (两性霉素B胶质复合体） Lower renal toxicity,Nystatin,Has the same mechanism with amphotericin B Only used topically for suppr
7、ession of local candidal infection,Azole,Imidazole Clotrimazole, miconazole, ketoconazole Triazole Fluconazole, itraconazole,Azole,Mechanism of action reduction of ergosterol synthesis by inhibition of fungal cytochrome P450-dependent 14- -demethylase Clinical uses Broad-spectrum: candida species, c
8、ryptococcus neoformans, and dermatophytes,Topical azoles: clotrimazole and miconazole,Broad spectrum Poorly absorbed Too toxic for systemic uses Topic use in treatment of dermatophytosis,Ketoconazole,The first broad-spectrum oral azole introduced into clinical use Treatment of mucocutaneous candidis
9、is and dermatophytosis Major toxicity: Endocrine disturbance: infertility, gynecomastia and menstrual irregularity Hepatoxicity: hepatitis Drug interaction,Itraconazole,Absorbed well F 55% Clinical uses Systemic fungal infection Choice in the treatment of dermatophytosis and onychomycosis Lower toxi
10、city than ketoconazole Can not penetrate BBB,Fluconazole,Can be adminstered orally and intravenously , high bioavalibility 95% Least effect on hepatic microsomal enzyme Drug of choice in the treatment of cyrptococcal menigitis (隐球菌性脑膜炎）of AIDS and other systemic fungal infections High concentration
11、in CSF,Other antifungal agents,Terbinafine(丁克） Inhibit fungal squalene epoxidase and interfere with ergosterol biosynthesis High effect and low toxicity Treatment of dermatophytoses especially onychomycosis(甲癣） Flucytosine Effective against cryptococcus and candida species Convert to 5-FU, inhibit D
12、NA synthesis Synergism with Amphotericin B,Antiviral drugs,Antiviral drugs,Acyclovir (ACV) Active against HSV-1 , HSV-2 Convert to ACV triphosphate and inhibit viral DNA polymerase Treatment of a variety of herpes infections include primary and recurrent genital herpes (one of the most effective),An
13、tiviral drugs,Idoxuridine（IDU） Active against HSV and VZV(牛痘病毒） Inhibit DNA synthesis by blocking thymidylic acid synthetase Topical use for treatment of HSV infections of the eyelid, cornea and skin High toxicity,Antiviral drugs,Ribavirin （virazole） Inhibit replication of both DNA and RNA viruses T
14、reatment of influenza A and B infections Teratogenesis Vidarabine （Ara-A） Convert to Ara-A triphosphate and inhibit DNA polymerase Active against HSV and vaccina virus Treatment of HSV encephalitis and herpetic keratitis,Antiviral drugs,Amantadine Inhibit penetration of virus to cells and the uncoat
15、ing of certain virus Prevent diseases caused by influenza A Treatment of Parkinsons disease,Anti-HIV drugs,Anti-HIV drugs,Nucleoside reverse transcriptase inhibitors(NRTIs, 核苷类逆转录酶抑制剂） Non-nucleoside reverse transcriptase inhibitors (NNRTIs, 核苷类逆转录酶抑制剂） Protease inhibitor(PI, 蛋白酶抑制剂） Cocktail therap
16、y,Nucleoside reverse transcriptase inhibitors (NRTIs),Zidovudine （齐多夫定，AZT, ZDV） Lamivudine(拉米夫定,3TC) Stavudine（司他夫定, d4T） Zalcitabine (扎西他宾, ddC） Didanosine (去羟肌苷, ddI） Abacavir (阿巴卡韦, ABC),Zidovudine （齐多夫定，AZT, ZDV）,The first reverse transcriptase inhibitor for treatment of AIDS Treatment of AIDS and HIV-associated dementia and thrombocytopenia Mechanism: Toxicity: myelosuppression,Non-nucleoside reverse transcriptase inhibitors,Delavirdine(地拉韦定） Nevirapine（奈韦拉平） Efavirenz （依法韦恩茨） Mechanism: different with NRTIs Used in combination with NRTIs and PI Toxicity: rash,
