抗肿瘤药 - 药理学.pptVIP

原则 1．根据细胞增殖动力学规律考虑联合用药 　招募作用：即设计细胞周期非特异和特异性药物序贯应用，驱动更多G0期细胞进入增殖周期，以增加肿瘤细胞杀灭数量。 　 　实体瘤(G0期细胞多)：先用周期非特异药物，后用周期特异药物 　急性白血病：用药先后与实体瘤相反 　同步化作用：即先用细胞周期特异性药物，将细胞阻滞于某一时相，待肿瘤细胞同步进入下一时相，再使用作用于后一期的药物。 2.从抗肿瘤药物的作用机制考虑联合用药 (1)序贯抑制：采用两种以上药物对同 一代谢途径不同阶段予以序贯性抑制 例：羟基脲 　　AraC ↓ 　 ↓ 　核苷酸还原酶 抑 DNA多聚酶 (2)互补抑制 抑制RNA合成的药物　+　直接损伤DNA的药物 例 阿霉素 + 环磷酰胺 ↑淋巴肉瘤及乳腺癌疗效 3.从毒性角度考虑联合用药 不同毒性药物合作，↑疗效，不↑毒性 如抑制骨髓药(多数抗癌药)+对骨髓抑制轻的药(泼尼松、VCR、博莱霉素) 4.从药物在体内分布、代谢角度考虑联合用药 长春新碱（VCR）可阻止MTX溢出胞外而增加胞内 MTX浓度，两药合用疗效↑，用大剂量 MTX前常先用 VCR 10 Rules to Avoid Cancer No smoking No smoking No smoking W/O known Carcinogens exposure, including aflatoxin, UV light…… Healthy diet (W/O drainage oil…… ) Eat fresh fruit and vegetables/day Be physically active and avoid obesity Vaccination protection, or early detection/ treatment of, cancer causing chronic infections Right genes Good luck ! * Surgery to remove solid tumors Radiation to kill cancer cells that have spread to adjacent local or regional tissues -patients without metastasis(~30%) -Respond to surgery and radiation -If diagnosed at early stage, close to 50% cancer could be cured Chemotherapy to kill cancer cells located throughout the body(Antineoplastic drugs cannot differentiate between normal and cancerous cells) - Is the use of drugs (antineoplastic agents) to kill tumor cells by interfering with cellular functions and reproduction - Synthetic treatment rather than a localized therapy such as surgery and radiation therapy - 50% patients will undergo chemo, to remove micrometastasis. However, chemo is able to cure only about 10-15% of all cancer patients * * * * 6-巯基嘌呤(6-mercaptopurine;6-MP) 机制： 肌苷酸 6-MP→硫代肌苷酸 　　　　　　　肌苷酸　　　　腺苷酸及鸟苷酸 适应症： 1.急淋：对儿童病人的疗效较佳，用于维持治疗 急粒、慢粒、单核粒 2.绒癌：疗效不如5-FU、MTX 3.免疫抑制：硫唑嘌呤较6-MP（前者代谢产物）更强、较持久，多用 嘌呤核苷酸互变抑制 羟基脲(hydroxyurea；HU) 机制： 抑制核苷酸还原酶 胞苷酸 脱氧胞苷酸 适应症： 1.慢粒：疗效不亚于白消安，二药无交叉耐药性。治后生存达50％以上 2.黑色素瘤 阿糖胞苷(cytarabin; AraC) 机制： 1.AraC