精品Trifluorothymidine（三氟胸腺嘧啶核苷）课件_8.pptVIP

Antiviral Agents;Overview;;Research in Antiviral Chemotherapy;Antiretroviral (Anti-HIV) Agents;病毒RNA;ViralRNA;Nucleoside Reverse Transcriptase Inhibitors;Mechanism of Action;Zidovudine;Decrease the rate of clinical disease progression and prolong survival. Treatment HIV-associated dementia(痴呆) and thrombocytopenia(血小板减少). Reduce the rate of vertical (mother-to-newborn) transmission of HIV. Adverse effect: myelosuppression(骨髓抑制) → anemia or neutropenia; gastrointestinal intolerance, headachs, insomnia(失眠);Zalcitabine (ddC);Stavudine;Adverse effects: Dose-limiting toxicity is a dose-related peripheral sensory neuropathy. Pancreatitis, arthralgias(关节痛), elevation in serum aminotransferases(转氨酶).;Didanosine (ddI);Adverse effects: Dose-dependent pancreatitis Painful peripheral distal neuropathy Diarrhea Hepatitis Esophageal ulceration(食管溃疡) Cardiomyopathy Central nervous system toxicity (headach, irritability, insomnia);Nonnucleoside reverse transcriptase inhibitors;Specific activity against HIV-1. Cross-resistance among this class of agents. The rapid emergence of resistance prohibits monotherapy with any of the NNRTIs. No cross-resistance between the NNRTIs and the NRTIs or the protease inhibitors. Oral bioavailability is high. Metabolized by the CYP3A P450 isoform, excreted in the urine. Adverse effects: skin rash;Protease inhibitors;Combination therapy with other agents is recommended to avoid emergence of resistance, because of specific genotypic alterations. Adverse effect: Syndrome of altered body fat distribution (buffalo hump and truncal obesity, with facial and peripheral atrophy) Insulin resistance Hyperlipidemia(高脂血症);Others Antiviral Agents;Nucleoside Antiviral Agents;Acyclovir (ACV);Mechanism: Three phosphorylation steps for activation. First converted to the monophosphate derivative by the virus-specified thymidine kinase;（selective activation） Then to the di- and triphosphate compounds by host’s cellular enzymes. Acyclovir triphosphate inhibits viral D