Although ^-adrenoceptor agonists (see Chapter 10) are the most commonly used tocolytic agents in the United States, they are not completely successful in treating preterm labor. Prophylactic administration of these agents to patients at high risk for preterm labor is not always effective. There is, however, clear evidence that (2-agonists can arrest preterm labor for at least 48 to 72 hours. The efficacy of these drugs beyond this time frame is in dispute. Even a short delay in delivery can be desirable, however, in that at very early preterm gestations (24-28 weeks) a 2-day delay in delivery may mean a 10 to 15% increase in probability of survival for the newborn. Furthermore, such a delay allows for cortico-steroid administration to the mother, which has been shown to decrease the incidence and severity of respiratory distress syndrome of the newborn, decrease the incidence of neonatal intraventricular hemorrhage, and improve survival in the premature newborn. Tocolysis also allows for the transport of the mother to a tertiary center where delivery of the preterm infant often results in its improved survival.
These drugs act by binding to ^-adrenoceptors on myometrial cell membranes and activating adenylyl cyclase. This in turn increases levels of cAMP in the cell (Fig. 62.1), activating cAMP-dependent protein kinase, hence decreasing intracellular calcium concentrations and reducing the effect of calcium on muscle contraction.
(2-Adrenergic drugs have many side effects. These result both from their residual ( activity and from their ability to stimulate (2-receptors elsewhere in the body (see Chapter 2). The side effects include palpitations, tremor, nausea, vomiting, nervousness, anxiety, chest pain, shortness of breath, hyperglycemia, hypokalemia, and hypotension. Serious complications of drug therapy are pulmonary edema, cardiac insufficiency, arrhythmias, myocardial ischemia, and maternal death.
Terbutaline (Brethine, Bricanyl) is a relatively specific ^-adrenoceptor agonist (see Chapters 10 and 39). Terbutaline can prevent premature labor, especially in individuals who are more than 20 weeks into gestation and have no indication of ruptured fetal membranes or in whom labor is not far advanced. Its effectiveness in premature labor after 33 weeks of gestation is much less clear. Terbutaline can decrease the frequency, intensity, and duration of uterine contractions through its ability to directly stimulate ^-adrenoceptors. While it appears to be especially selective for (2-receptor activation, terbutaline does have some ( activity as well.
Terbutaline should be initially used only in an appropriate hospital setting where any obstetric complications can be readily addressed. After initial administration, it can be used in the outpatient setting. Concomitant use of ( 2-adrenergic agonists and corti-costeroids have additional diabetic effects and may rarely lead to pulmonary edema. The combination of ( 2-adrenergic agonists and magnesium sulfate can cause cardiac disturbances, while coadministration of terbu-taline with other sympathomimetics can lead to the po-tentiation of the actions of the latter drugs.
Terbutaline is frequently used in the management of premature labor, although it has not been marketed for such use. Its effectiveness, side effects, precautions, and contraindications are similar to those of all ( 2-adrener-gic agonists. Terbutaline can cause tachycardia, hypotension, hyperglycemia, and hypokalemia. It can be given orally in addition to subcutaneous or intravenous administration.
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