Cremer K F, Pieper J A, Joyal M, Mehta J
Clin Pharmacol Ther. 1984 Nov;36(5):641-4. doi: 10.1038/clpt.1984.234.
Calcium channel blockers and antiplatelet agents, alone and in combination, have been reported to induce bleeding in patients undergoing surgery. Since diltiazem and dipyridamole influence platelet function in vitro and in vivo, their influence on hemostasis was examined in five normal men given diltiazem, 90 mg by mouth, followed by 60 mg every 6 hr for 48 hr, or dipyridamole, 75 mg by mouth every 8 hr for 48 hr. At 24 hr, the alternate drug was added to the regimen to assess effects of the combination on hemostasis. Platelet aggregation, serum thromboxane B2 and 6-keto-PGF1 alpha concentrations (stable metabolites of thromboxane A2 and prostacyclin), bleeding time, prothrombin time, partial thromboplastin time, and serum diltiazem concentrations were measured. Diltiazem and dipyridamole alone and in combination had no significant effect on bleeding time, prothrombin time, or partial thromboplastin time. Platelet aggregation induced by threshold concentrations of adenosine diphosphate, epinephrine, and calcium ionophore A 23187 were inhibited by diltiazem and dipyridamole alone and in combination. The only change in prostaglandin concentrations was a slight increase in serum 6-keto-PGF1 alpha after diltiazem. Despite influences on platelet function, neither diltiazem nor dipyridamole alone or in combination induced clinically relevant changes in hemostasis.
据报道，钙通道阻滞剂和抗血小板药物单独使用或联合使用时，会导致接受手术的患者出血。由于地尔硫䓬和双嘧达莫在体外和体内都会影响血小板功能，因此对5名正常男性进行了研究，观察它们对止血的影响。这5名男性口服90毫克地尔硫䓬，之后每6小时服用60毫克，持续48小时；或者每8小时口服75毫克双嘧达莫，持续48小时。在24小时时，将另一种药物添加到治疗方案中，以评估联合用药对止血的影响。测量了血小板聚集、血清血栓素B2和6-酮-前列腺素F1α浓度（血栓素A2和前列环素的稳定代谢产物）、出血时间、凝血酶原时间、部分凝血活酶时间以及血清地尔硫䓬浓度。地尔硫䓬和双嘧达莫单独使用及联合使用时，对出血时间、凝血酶原时间或部分凝血活酶时间均无显著影响。单独使用及联合使用地尔硫䓬和双嘧达莫时，均可抑制由阈浓度的二磷酸腺苷、肾上腺素和钙离子载体A 23187诱导的血小板聚集。前列腺素浓度的唯一变化是地尔硫䓬给药后血清6-酮-前列腺素F1α略有升高。尽管对血小板功能有影响，但地尔硫䓬和双嘧达莫单独使用或联合使用均未引起临床上与止血相关的变化。
