Munsterhjelm E, Niemi T T, Syrjälä M T, Ylikorkala O, Rosenberg P H
Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Hospital, PO Box 340 (P-floor), FIN-00029 HUS, Helsinki, Finland.
Br J Anaesth. 2003 Sep;91(3):357-62. doi: 10.1093/bja/aeg195.
Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects.
Ten healthy male volunteers (21-30 yr) were given diclofenac 1.1 mg kg(-1) alone, a combination of propacetamol 30 mg kg(-1) (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg(-1) or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22-24 h by photometric aggregometry, platelet function analyser (PFA-100(TM)) and by measuring the release of thromboxane B(2) (TxB(2)). Analgesia was assessed with the cold pressor test.
Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22-24 h, platelet function had fully recovered. TxB(2) release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100(TM) detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test.
The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.
对乙酰氨基酚（扑热息痛）可增强非甾体抗炎药（NSAIDs）的镇痛效果。对乙酰氨基酚是环氧化酶（COX）的弱抑制剂，其与NSAIDs联合使用可能会增加与COX抑制相关的副作用。
在一项双盲、交叉研究中，10名健康男性志愿者（21 - 30岁）被静脉注射单独的双氯芬酸1.1毫克/千克、丙帕他莫30毫克/千克（水解后50%为对乙酰氨基酚）与双氯芬酸1.1毫克/千克的组合或安慰剂。在5分钟、90分钟和22 - 24小时通过光度聚集法、血小板功能分析仪（PFA - 100™）以及测量血栓素B2（TxB2）的释放来评估血小板功能。通过冷加压试验评估镇痛效果。
在30分钟药物输注结束时，单独使用双氯芬酸和联合用药均能完全抑制花生四烯酸诱导的血小板聚集。丙帕他莫在90分钟时增强了双氯芬酸的抑制作用（P = 0.014）。在22 - 24小时，血小板功能已完全恢复。与单独使用双氯芬酸相比，丙帕他莫和双氯芬酸的组合在90分钟时抑制了TxB2的释放（P = 0.027）。PFA - 100™检测到这两组之间血小板功能无差异。冷加压试验未检测到镇痛效果。
丙帕他莫和双氯芬酸的组合比单独使用双氯芬酸更能抑制血小板功能。在评估手术出血风险时应考虑这一点。
