What is the mechanism of action of terbutaline in a pregnant woman at risk of preterm labor?

Mechanism of Action of Terbutaline in Preterm Labor

Terbutaline is a selective beta-2 adrenergic receptor agonist that inhibits uterine contractions by stimulating beta-2 receptors in the myometrium, leading to smooth muscle relaxation through increased intracellular cyclic AMP. 1

Pharmacological Mechanism

Receptor Selectivity and Action

• Terbutaline acts as a "selective" beta-2 receptor stimulator that directly inhibits uterine smooth muscle contractility 2, 1
• In vitro studies demonstrate that terbutaline at concentrations of 0.2-1.0 μg/ml effectively inhibits spontaneous contractile activity of isolated myometrial strips 1
• The uterine inhibitory effects are mediated specifically through beta-2 receptors, as evidenced by complete blockade with non-selective beta-blocker propranolol but not with selective beta-1 blockers like practolol 1

Clinical Efficacy in Uterine Inhibition

• Intravenous infusion of terbutaline at 10-15 μg/min for 20-40 minutes effectively inhibits both spontaneous and oxytocin-stimulated uterine activity 1
• A single intravenous bolus of 250 μg terbutaline provides safe and effective transient inhibition of uterine activity, particularly useful for acute intrauterine resuscitation when nonreassuring fetal heart rate patterns are associated with excessive contractions 3, 4
• Therapeutic plasma concentrations for cessation of uterine contractions range between 12.8 and 31.5 ng/ml 5

Clinical Application in Preterm Labor

Acute Tocolysis

• Terbutaline is appropriate for acute intrauterine resuscitation when nonreassuring fetal status is associated with excessive uterine contractions, provided no contraindications exist 3
• The success rate for inhibiting preterm labor for ≥48 hours is approximately 83.4%, allowing time for corticosteroid administration and maternal transfer 6
• In controlled trials, 80% of terbutaline-treated patients had premature labor arrested beyond the treatment period, compared to only 20% with placebo (p < 0.01) 2

Important Contraindications

• Maternal cardiovascular disease, tachycardia >100 bpm, thyrotoxicosis, or severe placental abruption are absolute contraindications 3
• Concurrent corticosteroid or atropine use contraindicates terbutaline administration 3
• The FDA explicitly warns that oral terbutaline should NOT be used for acute or maintenance tocolysis, particularly in outpatient or home settings 7

Maternal and Fetal Effects

Maternal Cardiovascular Effects

• Terbutaline causes a moderate increase in maternal heart rate (approximately 30% increase during infusion), which is the most common side effect occurring in 95.1% of patients 2, 6
• Systemic beta-2 agonist administration may cause maternal hyperglycemia and metabolic effects 3
• Serious adverse reactions with prolonged use include cardiac arrhythmias, pulmonary edema, myocardial ischemia, and maternal death have been reported 3, 7

Fetal Considerations

• Terbutaline crosses the placenta, with umbilical blood levels ranging from 11% to 48% of maternal blood levels 7
• Fetal tachycardia occurs more frequently with terbutaline but without other adverse fetal effects when used appropriately 2, 1
• Neonatal hypoglycemia may occur as a result of maternal administration 7

Pharmacokinetic Alterations in Pregnancy

• Plasma clearance is 29% higher during pregnancy compared to postpartum, resulting in decreased terminal half-life from 5.3 to 3.7 hours 5
• Mean steady-state plasma concentrations are approximately 30% lower during pregnancy than after delivery 5
• Volume of distribution remains unchanged during pregnancy 5

Critical Clinical Caveats

Appropriate Use

• Terbutaline is a temporizing measure only and should never substitute for timely delivery when indicated 3
• The primary purpose is to delay delivery for 48-72 hours to allow corticosteroid administration and maternal transfer to tertiary care facilities 8
• Tocolytic agents like terbutaline improve fetal heart rate tracings, though improvements in neonatal outcomes have not been definitively demonstrated 3

Common Pitfalls to Avoid

• Do not use terbutaline for maintenance tocolysis or in outpatient settings due to serious safety concerns 7
• Terbutaline may have a tocolytic effect during delivery itself, which should be considered when timing administration 3
• Prepare for expedited delivery if fetal status does not improve after terbutaline administration 3