本帖最后由 中庸之道 于 2010-10-29 17:48 编辑
治乙肝有门 发表于 2010-10-29 08:51
Aciclovir - 是不是阿昔洛韦?老师下次别用英文了,看不懂的.还有那个HSV-2怎么有的医生叫HPV呢? ...
(来源--维基百科) 阿昔洛韦(Aciclovir),又称无环鸟苷,是一种鸟嘌呤类似物类的抗病毒药物。阿昔洛韦是最常用的抗病毒药物之一,主要用于治疗单纯疱疹病毒感染,也用于带状疱疹的治疗。 阿昔洛韦曾因其极高的选择性和低细胞毒性而被视为是抗病毒治疗的新时代的开始,其发明者美国药理学家格特鲁德·B·埃利恩(Gertrude Belle Elion)也部分因此而获得1988年诺贝尔生理学或医学奖。 Aciclovir (INN) (pronounced /eɪˈsaɪklɵvɪər/) or acyclovir (USAN, former BAN), chemical name acycloguanosine, abbreviated as ACV,[1] is a guanosine analogue antiviral drug, marketed under trade names such as Cyclovir, Herpex, Acivir, Acivirax(Mash-Premier), Zovirax, Aciclovir (Sanofi-Aventis) and Zovir (GSK). One of the most commonly-used antiviral drugs, it is primarily used for the treatment of herpes simplex virus infections, as well as in the treatment of herpes zoster (shingles).
Aciclovir was seen as the start of a new era in antiviral therapy,[1] as it is extremely selective and low in cytotoxicity. Pharmacologist Gertrude B. Elion was awarded the 1988 Nobel Prize in Medicine, partly for the development of aciclovir. Dr. Richard Whitley, a University of Alabama at Birmingham researcher and pioneer in antiviral therapy, was the first to successfully use the drug in humans.
作用机理 阿昔洛韦与以前的核苷类似物类抗病毒药物不同,它只含有部分的核苷结构,其糖环被一条开放链取代。阿昔洛韦可被病毒胸腺嘧啶激酶(Thymidine Kinase, TK)催化磷酸化变成一磷酸无环鸟苷(acyclo-GMP),此过程比细胞胸腺嘧啶激酶快3000多倍。在细胞酶的催化下转变成二磷酸无环鸟苷(acyclo-GDP)及三磷酸无环鸟苷(acyclo-GTP)。acyclo-GMP是一种十分有效的DNA聚合酶抑制剂,它与病毒的亲和力是细胞聚合酶的100倍。作为酶作用物,acyclo-GTP与病毒的DNA结合,导致DNA链终止。同时,病毒酶不能将acyclo-GTP从DNA链上除去,从而导致DNA聚合酶的作用被进一步的抑制。可能是因为细胞磷酸酶的作用,acyclo-GTP在细胞中的代谢相当迅速。 Mechanism of action Aciclovir differs from previous nucleoside analogues in that it contains only a partial nucleoside structure: the sugar ring is replaced by an open-chain structure. It is selectively converted into acyclo-guanosine monophosphate (acyclo-GMP) by viral thymidine kinase, which is far more effective (3000 times) in phosphorylation than cellular thymidine kinase. Subsequently, the monophosphate form is further phosphorylated into the active triphosphate form, acyclo-guanosine triphosphate (acyclo-GTP), by cellular kinases. Acyclo-GTP is a very potent inhibitor of viral DNA polymerase; it has approximately 100 times greater affinity for viral than cellular polymerase. As a substrate, acyclo-GTP is incorporated into viral DNA, resulting in chain termination. It has also been shown that viral enzymes cannot remove acyclo-GTP from the chain, which results in inhibition of further activity of DNA polymerase. Acyclo-GTP is fairly rapidly metabolised within the cell, possibly by cellular phosphatases.
In sum, aciclovir can be considered a prodrug: it is administered in an inactive (or less active) form and is metabolised into a more active species after administration.
副作用 一般耐受性良好。局部用药有其轻度刺激症状,静脉滴注外渗可引起局部炎症和静脉炎,还有厌食、恶心、头痛和皮症。 To date, resistance to aciclovir has not been clinically significant. Mechanisms of resistance in HSV include deficient viral thymidine kinase; and mutations to viral thymidine kinase and/or DNA polymerase, altering substrate sensitivity.[3] Acyclovir has also shown cross-resistance with Valacyclovir and Famcyclovir |