Antiviral and antifungal drugs
Anti-HIV agents
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）
1. 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)
(1)
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
(2)
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
(3) Protease inhibitor
Drugs :saquinavir（沙奎那韦）, ritonavir(利托那韦）,indinavir（英地那韦）, nelfinavir（奈非
地韦）
Mechanism: inhibit precursor molecules convert to mature virions during HIV replication
Clinical uses: in combination with other agents to treat AIDS
Toxicity: abnormality in metabolism include altered body fat distribution, insulin resistance and
hyperlipidemia Other Antiviral agents
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)
2. Valacyclovir (伐昔洛韦）
Higher blood concentration
3.Ganciclovir
CMV
4.Vidarabine （Ara-A）
Convert to Ara-A triphosphate and inhibit DNA polymerase
Active against HSV, VZV, CMV, HBV etc/ Toxicity : neurotoxicity
Idoxuridine（IDU）
Inhibit DNA synthesis by blocking thymidylic acid synthetase
Topical use for treatment of HSV infections of the eyelid, cornea and skin
High toxicity
6. Ribavirin （virazole）
Inhibit replication of both DNA and RNA viruses
Treatment of influenza A and B infections
Teratogenesis
Lamivudine (3TC)
NRTIs: HIV-1/ One of the most effective drugs on HBV infection
Amantadine and rimantadine
Inhibit penetration of virus to cells and the uncoating of certain virus
Prevent diseases caused by influenza A
7. Foscarnet
8. Interferon
9. Polyinosinic polycytidylic acid
ANTIFUNGAL DRUGS
1. Fungal infection
Topical infection/ Systemic infection
2. Antifungal drugs
Antifungal antibiotics/ Azole: imidazole and triazole/ Others: terbinafine and flucytosine
3. Antifungal antibiotics
（1）Griseofulvin
①Antifungal activity
Inhibit the growth of dermatophytes include epidermophyton, microsporum and trichophyton
No effect on bacteria and systemic infections of fungi
②Mechanism of action: interfere with fungal nucleic acid synthesis
③Clinical use
only used in the systemic treatment of dermatophytosis include skin, hair and nails
④Adverse effects
Nausea, vomiting ,headache/ Allergic reaction: fever, skin rash and leukopenia
（2）Nystatin
 Has the same mechanism with amphotericin B
 Only used topically for suppression of local candidal infection
（3）Amphotericin B
①Antifungal activity: Has the broadest spectrum of antifungal action, Active against candida
albicans, cryptococcus neoformans, histoplasma capsulatum , bastomyces
②Mechanism 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 intracellular ions
and macromolecules leading to cell death
③Clinical uses
Drug of choice for nearly all life-threatening mycotic infections include severe fungal
pneumonia, crypotoccal meningitis or sepsis syndrome
④Adverse reactions
 Infusion-related toxicity: fever, chills, muscle spasm, headache, hypotension
 Renal damage: azotemia, K+ ,Mg2+ wasting
 Others: Liver damage, arrhythmia, anemia
4. Azole
（1）Drugs :
Imidazole: Clotrimazole, miconazole, ketoconazole
Triazole : Fluconazole, itraconazole
（2）Mechanism of action
Reduction of ergosterol synthesis by inhibition of fungal cytochrome P450-dependent 14-α
-demethylase
（3）Clinical uses
Broad spectrum: candida species, cryptococcus neoformans, dermatophytes
（4）Topical azoles: clotrimazole and miconazole
Poorly absorbed / Broad spectrum/ Too toxic for systemic uses/ Topical use in treatment of
dermatophytosis
（5）Ketoconazole
 The first broad-spectrum oral azole introduced into clinical use
 Treatment of mucocutaneous candidiasis and dermatophytosis
 Major toxicity:
Endocrine disturbance: infertility, gynecomastia and menstrual irregularity
Hepatoxicity: hepatitis
（6）Fluconazole
 Can be administered orally and intravenously, high bioavalibility
 Least effect on hepatic microsomal enzyme
 Drug of choice in the treatment of cyrptococcal meningitis and other systemic fungal
infections
（7）Itraconazole
 Can not penetrate BBB
 Choice in the treatment of dermatophytosis and onychomycosis
5. Other antifungal agents
（1）Terbinafine
 Inhibit fungal enzyme- squalene epoxidase and interfere with ergosterol biosynthesis
 Treatment of dermatophytosis especially onychomycosis
（2）Flucytosine
 Convert to 5-FU, inhibit DNA synthesis
Synergism with Amphotericin B, Effective against cryptococcus and candida species