Effects of diltiazem, dipyridamole, and their combination on hemostasis.
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.
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000328:Adult; D001552:Benzazepines / Q000494:pharmacology*; D001760:Bleeding Time; D001794:Blood Pressure / Q000187:drug effects; D000001:Calcimycin / Q000037:antagonists & inhibitors; D004110:Diltiazem / Q000097:blood / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000037:antagonists & inhibitors; D006339:Heart Rate / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D011517:Prothrombin Time; D013929:Thromboxane B2 / Q000097:blood
D001552:Benzazepines; D000001:Calcimycin; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D004110:Diltiazem; D004837:Epinephrine