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Tocolytics help eliminate uterine contractions by working on a variety of receptors, including oxytocin, voltage-gated L-type calcium channel, and acetylcholine receptors (Figure 154-1). The choice of agent is based on each clinical scenario.
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PHYSIOLOGY OF PRETERM LABOR
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The causes of preterm labor are multifactorial and vary according to gestational age. An extensive list of pathological processes has been implicated including decidual hemorrhage, myometrial and fetal membrane overdistention, precocious fetal endocrine activation, and infection/inflammation of the uterus. Tocolytic drugs are a group of medications responsible for the relaxation of the uterine myometrium, thus temporarily impeding labor. Tocolytics are generally employed during preterm labor under 35 weeks gestation age with the ultimate goal of delaying labor long enough for glucocorticoids to accelerate fetal lung maturity. It is important to note, however, that these medications are effective in delaying delivery but not in preventing premature births. Furthermore, tocolytics do not directly improve fetal outcome, but the opportunity they provide for glucocorticoid administration has been shown to improve fetal outcomes of prematurity.
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Tocolytic agents work by both inhibiting contraction and promoting relaxation of the uterine myometrium. Myometrial tone is increased when intracellular calcium levels become elevated, resulting in increased smooth muscle contractility via the calcium/calmodulin-dependent activation of myosin light-chain kinase. Tocolytic agents are successful in limiting calcium entry through L-type calcium channels and ligand-gated calcium channels, thereby preventing uterine contraction. Relaxation of the myometrium is favored when the cyclic nucleotides cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are increased leading to activation of protein kinases, which phosphorylate myosin light-chain kinase. This phosphorylation deactivates myosin light-chain kinase, which prevents contraction.
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TYPES OF TOCOLYTIC DRUGS
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β-Adrenergic Receptor Agonists
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Terbutaline is a β-adrenergic receptor agonist usually used as a fast-acting bronchodilator for asthma. However, off-label it is prescribed as a tocolytic and has been found to be effective in delaying preterm delivery for recommended maximum of 72 hours. Terbutaline activates the cAMP-protein kinase A (PKA) signaling cascade that phosphorylates and inactivates myosin light-chain kinase preventing contraction of the myometrium.
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Terbutaline can cause several adverse side effects including tachycardia, hypotension, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia. In the fetus, tachycardia and neonatal hypoglycemia may occur as side effects of maternal administration.
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The rate and duration of terbutaline administration should be altered in response to the patient’s response as measured by uterine response, maternal blood pressure (BP), and maternal and fetal heart rates. For acute tocolytic ...