Dinoprostone (Prostin E2) is a naturally occurring prostaglandin E2 found in mammalian tissues, human seminal plasma, and menstrual fluid (see Chapter 36). Carboprost tromethamine (Hemabate, Prostin/15M) is a synthetic analogue of the naturally occurring prostaglandin PGF2a. Both drugs stimulate uterine smooth muscle contractions and can be used to induce abortion during gestation weeks 12 to 20. Abortion was successful in 96% of the cases in which these agents were used, with complete passage of fetal products occurring more than 75% of the time without surgical intervention. The mean time to abortion after drug administration was 16 hours. The prostaglandins are more effective stimulants of uterine contraction through the second trimester of pregnancy than is oxytocin. Inhibition of endogenous prostaglandin synthesis with a non-steroidal antiinflammatory agent, such as aspirin or ibuprofen, can increase the length of gestation, prolong spontaneous labor, or interrupt premature labor.
Dinoprostone is slowly absorbed from the amniotic fluid into the systemic circulation. It and its metabolites readily cross the placenta and can concentrate in the fetal liver. Dinoprostone is primarily metabolized in the maternal lungs and liver and has a half-life in plasma and amniotic fluid of less than 1 minute and 3 to 6 hours, respectively. Carboprost also is metabolized in maternal lung and liver but somewhat more slowly than dinopro-stone. It is primarily eliminated by renal excretion of its metabolites, with small amounts appearing in the feces.
Because dinoprostone produces cervical ripening along with stimulation of the uterus, it has been used as an alternative to oxytocin for the induction of labor. Preparations of dinoprostone can be placed in either the cervix or the posterior fornix. Prepidil is a formulation and delivery system of dinoprostone that delivers a dose of 0.5 mg into the cervix, while Cervidil consists of the drug embedded in a plastic matrix. The matrix is designed to deliver a dose of 0.3 mg per hour for 12 hours.
Carboprost has been used successfully to control postpartum bleeding that was secondary to loss of uterine tone and where the myometrium was unresponsive to oxytocin, ergonovine, or methylergonovine. Given intramuscularly, carboprost causes an almost immediate and sustained uterine contraction. Clinical experience has shown that the use of this agent has saved many women from operative interventions (including hysterectomy) to control postpartum hemorrhage.
Misoprostol (Cytotec) is a prostaglandin Ej analogue that is being evaluated as a cervical ripening agent. It also is used in the treatment and prevention of peptic ulcer disease (see Chapter 40). Clinical trials show that misoprostol is an effective agent for both cervical ripening and labor induction. It appears to be as effective as dinoprostone and is much less expensive.
While adverse reactions are common following the use of abortion-inducing doses of the prostaglandins, most are not serious. Gastrointestinal disturbances include nausea, vomiting, and diarrhea. Transient fever, retained placental fragments, excessive bleeding, decreased diastolic blood pressure, and headache also have been noted. These drugs should be used with caution in patients with asthma, cervicitis, vaginitis, hypertension or hypotension, anemia, jaundice, diabetes, or epilepsy. They should not be used in patients with acute pelvic inflammatory disease, drug hypersensitivity, or an active renal, hepatic, or cardiovascular disorder. Since prostaglandins are potentially carcinogenic, if pregnancy is not effectively terminated following their use, another method should be used. The prostaglandins are not generally used concomitantly with oxytocin because of the possibility of uterine rupture.
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