dinoprost and Nausea

In a prospective, open-label, assessor-blind, randomised parallel group study the efficacy and safety of Hemabate (Pharmacia-Upjohn Pharmaceuticals, Milton Keynes, Buckinghamshire) an analogue of 15-methyl-prostaglandin (PGF2alpha) analogue was compared with Syntometrine (Alliance Pharmaceuticals, Chippenham, Wilts) the standard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage (PPH). The study was set in a district general hospital with approximately 4,000 deliveries annually. The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects. At the time of the interim analysis, a total of 529 women had completed the study with 263 randomised to receive PGF2alpha and 266 to receive ergometrine and syntocinon. In a pre-specified subgroup analysis, women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH. The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk. Adverse gastrointestinal events were recorded more often in the Hemabate group. The most common symptom was diarrhoea which occurred in 21% of women who received Hemabate compared to only 0.8% of Syntometrine users. PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha.

Topics: Adult; Blood Pressure; Body Height; Body Weight; Carboprost; Cesarean Section; Dinoprost; Disease Susceptibility; Drug Combinations; Ergonovine; Female; Gastrointestinal Diseases; Humans; Nausea; Oxytocin; Parity; Postpartum Hemorrhage; Pregnancy; Random Allocation; Single-Blind Method; Tromethamine

Cervical dilatation and softening after pretreatment with mifepristone are well documented. As this effect is similar to that observed after local application of prostaglandin E2 (PGE2) it is tempting to speculate that the effect of mifepristone is mediated via an increase of the endogenous secretion of prostaglandins from the cervical mucosa. Eighteen healthy women in the first trimester of pregnancy were treated with oral mifepristone (200 mg) 48 and 24 hours before legal abortion by vacuum aspiration and 18 women in the same age of gestation without any pretreatment served as controls. Cervical mucus was collected for measurement of prostaglandins by radioimmunoassay before administration of the drug and in connection with vacuum aspiration. The cervical dilatation at the time of surgery was significantly increased in women given mifepristone as compared with untreated women (7.6 versus 5.8 mm). The wet weight of collected cervical mucus was significantly increased in mifepristone treated women. The amount of PGE2 and prostaglandin F2 alpha per sample was unchanged in mifepristone-treated women, whereas the concentration was lower as an effect of dilution due to an increased yield in cervical secretion observed after mifepristone treatment. The present observation does not give any support to the hypothesis that mifepristone-induced cervical maturation is mediated via an increase in cervical prostaglandin production.

Topics: Abortion, Legal; Adult; Cervix Mucus; Cervix Uteri; Chlamydia Infections; Chlamydia trachomatis; Dilatation and Curettage; Dinoprost; Dinoprostone; Female; Gestational Age; Humans; Mifepristone; Nausea; Pregnancy; Pregnancy Trimester, First; Time Factors; Vaginosis, Bacterial

Peripheral plasma prostaglandins (PGs) were assayed in 10 cases of gynecologic malignancies. In addition, fluctuations of PG levels during chemotherapeutically-induced gastrointestinal toxicity as well as those caused by a bolus infusion of steroid hormone were investigated. As a result, the level of PGE2 in most cases of gynecologic malignancies was seen above or around the upper limit of that in healthy women. During chemotherapy, the levels of PGF2 alpha and thromboxane B2 (TxB2) increased significantly compared to baseline levels (P less than 0.05). A bolus infusion of steroid hormone did not bring about any noticeable change in any of the levels of PGF2 alpha, TxB2, PGE2 or 6K. It may be inferred from these findings that PGs are synthesized in tumor tissue itself and released into plasma. Also, the finding that the levels of peripheral plasma PGs increased during chemotherapy suggested that such an increase in PG release could be one of the factors causing gastrointestinal toxicity. Based on the fact that there were no changes in levels of peripheral plasma PGs due to the administration of steroid hormone, however, we failed to support the proposal that steroid hormone suppresses the release of PG.

Topics: 6-Ketoprostaglandin F1 alpha; Antineoplastic Combined Chemotherapy Protocols; Dinoprost; Dinoprostone; Female; Humans; Hydrocortisone; Nausea; Ovarian Neoplasms; Prostaglandins; Prostaglandins E; Prostaglandins F; Radioimmunoassay; Thromboxane B2; Uterine Neoplasms; Vomiting

The introduction of dinoprost tromethamine (Prostin F2 Alpha) as an abortifacient in the second trimester of pregnancy represents the first clinical use of a prostaglandin. Various synthetic analogues of the naturally occurring derivatives are being employed investigationally in the treatment of peptic ulcer, hypertension, asthma, and hypercalcemia. In the United States, dinoprost tromethamine is primarily administered intra-amniotically. Despite the fact that a substantial number of patients experience allergic reactions, hypertension, bronchospasm, nausea, vomiting, cramps, and diarrhea, the efficacy and relative safety of dinoprost tromethamine establish it as superior to intra-amniotic instillation of hypertonic saline. Cervical laceration, laceration or rupture of the lower uterine segment, retention of the placenta, and hemorrhage in part reflect the intensity of uterine contraction induced by dinoprost. Experience in administration improves the therapeutic response and diminishes adverse reactions.

Topics: Abortifacient Agents; Bronchial Spasm; Diarrhea; Dinoprost; Dose-Response Relationship, Drug; Drug Evaluation; Drug Hypersensitivity; Female; Humans; Hypertension; Injections; Muscle Contraction; Myometrium; Nausea; Pregnancy; Pregnancy Trimester, Second; Prostaglandins F; Vomiting