32：抗病毒药

抗病毒药1.概述自40年代抗生素问世以来，许多细菌性疾病得到了有效控制，而防治病毒性疾病则比治疗细菌性疾病要困难的多，已成为目前传染性疾病的突出问题，由于病毒的结构和增殖方式不同于细菌，他们自身缺乏繁殖的酶系统，必须寄生在宿主的细胞内。借助于宿主细胞的酶系统合成自身的核酸和蛋白质才能生长繁殖，这就使药物在对病毒产生作用的同时也可杀伤宿主的正常细胞，故使抗病毒药的应用受到了一定的限制。近年来虽筛选出了一些抗病毒药，但他们的抗病毒谱较狭窄，只限于对一种或几种病毒，因此，寻找新的有效的抗病毒药，特别是对病毒有选择性毒性而对宿主细胞无害的药物仍是当前迫切而重要的任务。1.1病毒的繁殖过程 病毒以复制方式繁殖，这一作用是在宿主细胞内完成的，从病毒感染宿主细胞到子代病毒从细胞释放为一繁殖周期。包括细胞吸附于细胞膜上的受体，继之穿入细胞，在细胞内脱去蛋质外壳，释放出感染性核酸，并进行生物合成（包括核酸的复制、转录与蛋白质合成），最后合成的核酸与蛋白质装配成子代病毒颗粒， 并被细胞释放，再感染新的细胞。1.2抗病毒药的作用机制1.2.1与病毒竞争细胞膜表面的受体，阻止病毒的吸附，如肝素和带阴电荷的多糖。1.2.2阻止病毒穿入和脱壳，如金刚烷胺能抑制流感病毒的脱壳而预防流感。1.2.3阻碍病毒的生物合成，如疱疹净抑制胸腺嘧啶核苷合成酶，影响dna的合成；阿糖腺苷，阿糖胞苷干扰DNA聚合酶，阻碍DNA的合成；吗林啉双胍对病毒增殖周期各个阶段几乎均有抑制作用（主要是阻抑RNA聚合酶的活性及蛋白质的合成）。此外，某些药物可被由病毒基因编码的酶（如胸苷激酶0磷酸化，该磷酸化物为病毒DNA聚合酶的底物，二者结合后就可发挥抑制酶的作用，因而，可阻止病毒DNA的合成，如无环鸟苷。1.2.4增强宿主抗病力的物质，如干扰素能激活宿主细胞的某些酶，从而抑制病毒合成蛋白质。2.种抗病毒药 金刚烷胺（金刚胺）为人工合成的饱和三环葵烷的胺基衍生物，白色结晶，性质稳定，易溶于水。一般用其盐酸盐。作用 1964年Davies等首先报告了金刚烷胺的抗病毒作用。它不是影响病毒与细胞的结合，也不影响其穿入，可能是通过阻止病毒脱壳而抑制甲型流感病毒的早期的复制与增殖。多数甲型流感病毒株及其亚型均可被0。4微克/毫升或更底浓度的金刚烷胺所抑制。高浓度时（2550微克/毫升）可抑制乙型流感病毒、风疹和其他病毒。组织培养及动物实验表明，该药能有效的预防不同株的流感病毒所引起的感染，用于与流感病人密切接触的人，特别适用于在医院和团体单位使用。对已经发病的患者，只要治疗及时，也能加速症状的消失。一般在用药24小时之内可使体温明显下降，36小时内其他症状也显著改善，并能缩短病程，减少并发症。在甲型流感病毒感染的病人中，用双盲法及安慰剂对照研究证明，在发病48小时以内给予金刚烷胺仍可发挥治疗作用。对动物的流感病毒同样有效。体内过程 口服后，在胃肠道几乎完全吸收。在体内不被代谢，主要由肾脏排出，约口服量的90%以原型由尿排出。一次口服后，一周内仍可从尿中排出。本品在人的半衰期为20个小时。易通过生物膜，脑脊液中的浓度为血浆浓度的60%。服药30小时后，唾液中的浓度接近血浆水平。在动物中的药物代谢动力学参数目前还未见报道。用途 主要用于甲型流感病毒的感染，特别当该病毒的变异株引起流感大流行而疫苗尚不能使用时，该药的应用价值更大。本品不影响流感疫苗的免疫反应，所以病人可以同时使用疫苗，2周后停用金刚烷。据报道，本品只能使半数病人免于得病，失败的原因之一可能是病毒产生了耐药性，不过应用本药预防后，即使仍被感染，其症状也较轻。也试用于带状疱疹病毒或淋巴细胞性脉络丛脑膜炎。本品用于防治禽流感，对鹌鹑流感死亡率可减少50%，对火鸡可使症状减轻，可使鸡流感的死亡率明显降低，但感染率不受影响并仍然排出病毒，鸡用量过大会明显影响食欲，导致中毒，1998年秋天，禽流感在山东开始大流行，有人用本品预防，结果导致产蛋率急剧下降。 不良反应 用于防治流感，人0.1克/次，每日两次，即每天的用量200毫克，用量过大，副作用明显增多。鸡510毫克/公斤体重。 吗啉双胍又叫吗啉胍，其盐酸盐也叫病毒灵，是60年代初合成的双胍类抗病毒药，为广谱抗病毒药。抗病毒谱较广，对甲、乙型流感病毒，副粘病毒、鼻病毒、呼吸道合包体病毒等RNA病毒有作用，对DNA病毒也有一定的作用，其抗病毒机理是抑制病毒的增殖，对增殖周期的各阶段几乎均有抑制作用，但主要是阻止RNA聚合酶的活性及蛋白质的合成。该药内服容易吸收、排泄也快。主要用于防治流感，流行性腮腺炎，疱疹，眼结膜炎，小儿秋季腹泻。可用于动物的病毒性疾病的防治鸡：510毫克/公斤体重。三氮唑核苷也叫病毒唑，利巴韦林，为广谱抗病毒药。作用 组织培养与动物实验证明，本药对多种DNA及RNA病毒有效，包括疱疹病毒、痘病毒、流感病毒、副流感病毒、鼻病毒、肠病毒。抗病毒机理为：在体内转变成它的磷酸盐，来竞争性的抑制单磷酸肌苷脱氢酶，导致鸟苷-5-磷酸盐难以合成。使DNA、RNA的合成受阻。对流感病毒还能抑制其蛋白质的合成。它能浓集于人的红细胞。用途用于防治多种病毒感染。用量过大（人每日超过900毫克）可导致贫血、白细胞减少等造血系统的变化，其原因不明。动物试验证明本品有致畸的毒性，故孕妇特别是妊娠前三个月内禁用。动物使用时也应注意。主要用于动物的流感治疗。 QcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3P tGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgK 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 tGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2tGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv HhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGshLs50cLmTWN60eo8Wgqv7XAv2OHUm32WGeaUwYDIAWGMeR4I30kA1DkaGhn3XtKknBYCUDxqA7FHYi2CHhI92tgKQcWA3PtGZ7R4I30kA1DkaGtgKQcWA3PtGZ7R4I30