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ceptor agonists, nitric oxide donors, and magnesium sulfate and the calcium channel blockers. The second group includes prostaglandin synthesis inhibitors and oxytocin antagonists.

Randomized, controlled trials of tocolytics have shown that they successfully inhibit contractions for 2 to 7 days. They have not been useful for long-term maintenance of contraction inhibition and in most studies have not improved perinatal outcomes, although their use does allow time for the administration of corticosteroids and maternal transfer to an appropriate hospital.


Magnesium sulfate The precise mechanism by which magnesium affects uterine contractions has not been completely elucidated. Magnesium likely competes with calcium at the level of plasma membrane voltage-gated channels. It hyperpolarizes the plasma membrane and inhibits myosin light-chain kinase activity by competing with intracellular calcium at this site. Interference with the activity of myosin light-chain kinase reduces myometrial contractility (Cunze et al., 1995; Lemancewicz et al., 2000; Mizuki et al., 1993). In two randomized, placebo-controlled trials of magnesium sulfate, magnesium sulfate did not lead to improved birth outcomes, although the cessation of contractions for a short interval was demonstrated (Cox et al., 1990; Fox et al., 1993). Three of four randomized clinical trials that compared magnesium sulfate with terbutaline found no difference in perinatal outcomes (Berkman et al., 2003). Meta-analysis also indicates that magnesium sulfate is ineffective for the treatment of preterm labor (Crowther et al., 2002). Potential adverse effects of magnesium sulfate include respiratory depression, flushing, nausea, and pulmonary edema.


Beta-mimetic drugs The β-adrenergic receptor agonists cause myometrial relaxation by binding with β2-adrenergic receptors and increasing intracellular adenyl cyclase. An increase in intracellular cyclic adenosine monophosphate levels activates protein kinase, which results in the phosphorylation of intracellular proteins. The resultant drop in intracellular free calcium levels interferes with the activity of myosin light-chain kinase, which inhibits the interaction between actin and myosin, and thus, myometrial contractility is diminished (Caritis et al., 1979, 1987, 1991).

Beta-sympathomimetic drugs, including terbutaline and ritodrine, have been widely used as tocolytics for many years. The most commonly used beta-mimetic in the United States is terbutaline (marketed in the United States as a drug for the treatment of asthma); but others, including albuterol, fenoterol, hexoprenaline, metaproterenol, nylidrin, orciprenaline, and salbutamol, are used in other countries. Ritodrine hydrochloride, the only drug ever approved for use as a parenteral tocolytic by the Food and Drug Administration (FDA), never achieved widespread use because of frequent



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