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1What drug interactions may occur with warfarin?
2What drugs alter prothrombin time by interacting with warfarin levels (pharmacokinetics)?
3What drugs alter prothrombin time, but not by changing warfarin levels (pharmacodynamics)?
1 哪些药物可与华法林相互影响？
2 哪些药物可通过影响华法林水平改变凝血酶原时间（药代动力学角度）？
3 哪些药物不是通过影响华法林水平而改变凝血酶原时间（药效动力学角度）？

参考答案
1 哪些药物可与华法林相互影响的？
许多药物与华法林一起使用后，对华法林的疗效可能无影响，也可能增强或拮抗抗凝作用。随着合并用药的增加和新药物的不断引进，相互作用的列表不断更新（表1, 2, 3)）。最近草药和华法林的相互作用引起人们重视，如有文献报道华法林和银杏片合用时增加了出血几率。
随着科学家们对药物的相互作用认识的不断深入，华法林和其他药物独立的或依赖性作用也逐渐明了。Dozal等研究了可改变3种维生素K类型（所有的电子受体）的电子传递供体-受体复合物和噻嗪类精神药物、抗菌剂、抗疟药、抗生素和抗凝剂等间的相互作用。有趣的是，在发生快速化学反应后，抗凝剂华法林、香豆素、双香豆素只是短暂合成。相反，许多噻嗪类精神药物、抗菌剂、抗疟药、抗生素和抗凝剂与维生素K相互作用形成牢固的供体-受体复合物，而此时此相互作的抗凝效应还未检测到，华法林与这些药物合用后抗凝效应增强可能与此现象有关。
2 哪些药物可通过影响华法林水平改变凝血酶原时间（药代动力学角度）？
 
3 哪些药物不是通过影响华法林水平而改变凝血酶原时间（药效动力学角度）？

Table 3: 可改变凝血酶原时间，但作用机制
不明的药物 (1)

英文参考答案：
1.What drug interactions may occur with warfarin?
The concurrent use of warfarin with a number of medications may mimic, magnify, or oppose its intended action. The list of interactions (Tables 1, 2, 3) grows with the increased use of drug combinations and the introduction of new drugs (1). Most recently, herbal remedy-warfarin interactions, such as the increased bleeding when warfarin is combined with ginkgo (Ginkgo biloba), has been reported (2).
As the science to investigate these interactions improves, additional information on the independent and dependent reactions of warfarin and other medications is unveiled. Dozal et al. (3), studied the charge transfer donor (D)-acceptor (A) complexes which form between three classes of vitamin K (all electron acceptors) and several thiazine psychotropes, antimicrobials, antimalarials, antibiotics, and anticoagulants. Interestingly, the anticoagulants warfarin, coumarin, and dicumarol, formed only temporary complexes before proceeding rapidly to chemical reaction. By contrast, many thiazine antimicrobials, antimalarials and antibiotics formed strong donor-acceptor interactions with vitamin K. While the anticoagulant effect of this interaction was not examined, potentially this may be responsible for the increased anticoagulant effect observed with warfarin in the presence of these drugs.
2.What drugs alter prothrombin time by interacting with warfarin levels (pharmacokinetics) (1)?
 

3.What drugs alter prothrombin time, but not by changing warfarin levels (pharmacodynamics) (1)?
 
Table 3: Drugs which alter prothrombin time, but the mechanism
is not known (1)

References:
1.Hirsh J. Oral anticoagulant drugs. N Engl J Med 1991;324:1865.
2.Fugh-Berman A. Herb-drug interactions. Lancet 2000 Jan 8;355(9198):134-8
3.Dozal A, Keyzer H, Kim HK, Wang WW. Charge transfer complexes of K vitamins with several classes of antimicrobials. Int J Antimicrob Agents 2000 Apr;14(3):261-5