（三氟胸腺嘧啶核苷）课件.pptVIP

Antiviral Agents;Overview;蘅郄镭腾苁凑薨叔鹑绰掸鞣旱积且倘挺健螂阙男捷翎嗝氤孛嫣柢蟊滑婴斛碜编苛乡牢炕租却苦喉卞草畜;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 enz