Effects of a thromboxane synthetase inhibitor on platelet function; possible risks of use in pregnancy.
It has been proposed that thromboxane synthetase inhibitors may be of use in the treatment of hypertensive disorders of pregnancy. A patient in whom aspirin did not prevent the development of pre-eclampsia in a previous pregnancy was treated with a thromboxane synthetase inhibitor (dazmegrel, Pfizer) in addition to low-dose aspirin. Increased urinary levels of 6-keto-prostaglandin F1 alpha were found throughout pregnancy, which is consistent with the mode of action. At 17-18 weeks of gestation urinary prostaglandin E2 and F2 alpha levels were increased compared with control pregnancies. These increases in PGE2 and PGF2 alpha production were associated with mid-trimester abortion. In vitro studies were carried out to determine the effects of dazmegrel on platelet eicosanoid production. In whole blood from non-pregnant female volunteers this compound inhibited thromboxane B2 production and significantly enhanced prostaglandin E2 production and slightly increased prostacyclin production, demonstrating a redirection of prostaglandin endoperoxides. This suggested that similar changes in arachidonic acid metabolite production may occur in vivo and in vitro, and that thromboxane synthetase inhibitors should not be used during early pregnancy, since increased production of prostaglandins E2 and F2 alpha may result in preterm labour or abortion.
Institute of Obstetrics and Gynaecology, Royal Postgraduate School, Hammersmith Hospital, London, U.K.
M H
MH
Sullivan
Y
Y
Ahmed
M G
MG
Elder
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis / Q000097:blood / Q000652:urine; D001792:Blood Platelets / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D000075202:Contraindications; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood / Q000652:urine; D015777:Eicosanoids / Q000097:blood*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011247:Pregnancy; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D015777:Eicosanoids; D007093:Imidazoles; C039242:dazmegrel; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003094:Collagen; D013930:Thromboxane-A Synthase; D015232:Dinoprostone