Tocolytics
High-yield Verified · Oct 2026Three ways to keep calcium from contracting the uterus — and three different organs that pay for it.
Nursing view → administration, monitoring and patient teaching
Compare: Labor drugs compared — uterotonics, tocolytics and magnesium sulfate →
Drugs
Mechanism
Terbutaline stimulates β2-adrenergic receptors, activating adenyl cyclase and raising cAMP, which relaxes smooth muscle. Nifedipine inhibits calcium entry into uterine smooth muscle, so calcium–calmodulin cannot activate myosin light chain kinase. Indomethacin inhibits cyclooxygenase, reducing prostaglandin production from arachidonic acid.
How the myometrium contracts
Myometrial contraction, like that of all smooth muscle, is calcium-mediated and needs no nerve or hormonal trigger to start. A spontaneous depolarization opens voltage-gated calcium channels; the incoming calcium binds calmodulin, and the complex activates myosin light chain kinase, which phosphorylates myosin light chains so the myosin heads cycle on actin. Tocolytics quiet this contraction by different mechanisms.
Terbutaline: β2 relaxation, β1 side effects
Terbutaline is a β-adrenergic agonist with a preferential effect on β2 receptors. It stimulates adenylyl cyclase, converting ATP to cAMP, and increased cAMP is associated with smooth muscle relaxation — in the bronchi, which is its labeled use, and in the myometrium. But β2 selectivity is relative: a population of β2 receptors exists in the human heart, subcutaneous terbutaline has shown no preferential β2 effect in controlled studies, and its maternal cardiac complications are suggested to stem from activity at β1 receptors.
The labels list the consequences in pregnancy: increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema and myocardial ischemia, with deaths reported. Hypokalemia, possibly from potassium shifting into cells, is usually transient. Increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration, and terbutaline crosses the placenta. Its boxed warning cites these reactions: no injectable tocolysis beyond 48 to 72 hours, no oral tocolysis at all, and no maintenance tocolysis at home.
Nifedipine and indomethacin
Nifedipine inhibits calcium entry into uterine smooth muscle, so calcium–calmodulin cannot activate myosin light chain kinase; it is the most common calcium channel blocker used (Calcium channel blockers page). Its maternal risks include flushing, headache, dizziness, nausea and hypotension, so it is used with great caution in women with hypotension or cardiac conditions.
Indomethacin inhibits cyclooxygenase, which makes prostaglandins from arachidonic acid (NSAIDs page). Blocking prostaglandins also constricts the renal afferent arteriole. In the fetus, NSAIDs at about 30 weeks and later increase the risk of premature closure of the ductus arteriosus, and from about 20 weeks can cause fetal renal dysfunction and oligohydramnios; StatPearls also lists fetal gastric perforation and pulmonary hypertension.
Why tocolysis is short-term
Tocolysis is meant to prolong gestation by two to seven days, not to term. That window allows transfer to a higher-level facility, a course of antenatal corticosteroids for fetal lung maturity (Corticosteroids page), and GBS prophylaxis; typically 48 hours of medication bridges the steroid window. It benefits preterm labor before 34 weeks, is not recommended as prophylaxis, and evidence does not support β-agonists, calcium channel blockers or COX inhibitors for maintenance tocolysis. Magnesium sulfate is covered on its own page.
Progesterone and hydroxyprogesterone caproate have limited data for maintenance and may be used in women with a history of preterm labor, but they are not considered tocolytic agents.
Comparing the drugs
Tocolytics compared
| Drug | Mechanism | Label status for tocolysis | Main maternal risk | Main fetal or neonatal risk |
|---|---|---|---|---|
| Terbutaline | β2 agonist → ↑ cAMP | Not approved; boxed against prolonged (injection) or any oral tocolysis | Tachycardia, arrhythmia, pulmonary edema, hyperglycemia, hypokalemia | Fetal tachycardia; neonatal hypoglycemia |
| Nifedipine | Blocks calcium entry into myometrium | Off-label (labeled for angina) | Hypotension, flushing, headache | — |
| Indomethacin | COX inhibition → ↓ prostaglandins | Off-label (labeled for arthritis and gout); NSAID box | GI bleeding; renal vasoconstriction | Ductus arteriosus closure (≥ ~30 weeks); oligohydramnios (≥ ~20 weeks) |
Pharmacokinetics
- Terbutaline
- After subcutaneous injection, peak levels occur at a median of about 30 minutes; the mean terminal half-life was 5.7 hours in one study, and about 2.9 hours in most patients in another. About 90% is excreted in the urine, around 60% unchanged, and it crosses the placenta (umbilical levels 11–48% of maternal).
- Nifedipine
- Metabolized by CYP3A4: phenytoin lowers its exposure by about 70%, and grapefruit juice about doubles it.
Uses & drug choice
- Terbutaline — labeled only for prevention and reversal of bronchospasm in patients 12 years and older; it is not approved for tocolysis and is boxed against prolonged (injection) or any oral tocolysis
- Nifedipine — labeled for vasospastic and chronic stable angina; used off-label as a tocolytic
- Indomethacin — labeled for rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, acute painful shoulder and acute gouty arthritis; used off-label as a tocolytic
Adverse effects
- Maternal tachycardia, arrhythmia, myocardial ischemia (terbutaline)
- Suggested to stem from β1 activity in cardiac muscle; β2 receptors are also present in the human heart.
- Hypokalemia (terbutaline)
- Possibly intracellular shifting of potassium by β-agonists.
- Hyperglycemia and neonatal hypoglycemia (terbutaline)
- β-adrenergic metabolic effects in the mother; placental transfer to the fetus.
- Hypotension, flushing, headache (nifedipine)
- Nifedipine’s hypotensive effect; occasional patients have excessive, poorly tolerated hypotension.
- Premature ductal closure, oligohydramnios (indomethacin)
- NSAID effects on the fetus: ductal closure from about 30 weeks, renal dysfunction from about 20 weeks.
Interactions
Contraindications
- Terbutaline injection — prolonged tocolysis beyond 48–72 hours, or maintenance tocolysis at home — Labeled contraindication and boxed warning — serious maternal cardiopulmonary reactions and deaths.
- Terbutaline tablets — acute or maintenance tocolysis — Labeled contraindication and boxed warning.
- Terbutaline — hypersensitivity to sympathomimetic amines — Labeled contraindication.
- Indomethacin — aspirin or NSAID hypersensitivity (asthma, urticaria), known hypersensitivity, or CABG surgery — Labeled contraindications.
- Indomethacin — pregnancy at about 30 weeks of gestation or later use caution — Avoid: risk of premature closure of the fetal ductus arteriosus.
- Terbutaline — cardiovascular disorders (ischemic heart disease, arrhythmias, hypertension), hyperthyroidism, diabetes, seizure disorders use caution — Use with caution: sympathomimetic cardiovascular and metabolic effects.
- Nifedipine — maternal hypotension or cardiac conditions use caution — Use with great caution in tocolysis because of hypotension.
High-yield
Practice questions
Q1A 28-year-old woman at 30 weeks in preterm labor receives subcutaneous terbutaline. An hour later her heart rate is 132/min, she reports chest tightness, her glucose is 186 mg/dL and her potassium is 3.1 mEq/L.
What best explains these findings?
- A.Blockade of β2 receptors in the uterus and lungs
- B.Calcium channel blockade with reflex tachycardia
- C.β-adrenergic stimulation — cardiac β1 activity and β-agonist metabolic effects
- D.Inhibition of prostaglandin synthesis
Show answer
C. β-adrenergic stimulation — cardiac β1 activity and β-agonist metabolic effects — Terbutaline is a β-adrenergic agonist; its maternal cardiac complications are suggested to stem from β1 activity in cardiac muscle, and β-agonists cause transient hyperglycemia and hypokalemia, possibly from intracellular potassium shifting. It stimulates rather than blocks β2 receptors. Calcium channel blockade is how nifedipine works, and prostaglandin synthesis inhibition is indomethacin’s mechanism.
Q2A 32-year-old woman at 31 weeks has preterm contractions. The team considers indomethacin as a tocolytic.
Which fetal risk is the main reason to avoid it at this gestational age?
- A.Premature closure of the fetal ductus arteriosus
- B.Fetal tachycardia
- C.Neonatal hypoglycemia
- D.Maternal hypokalemia
Show answer
A. Premature closure of the fetal ductus arteriosus — NSAIDs, including indomethacin, at about 30 weeks of gestation and later increase the risk of premature closure of the fetal ductus arteriosus, and from about 20 weeks they can cause fetal renal dysfunction leading to oligohydramnios. Neonatal hypoglycemia and fetal tachycardia are terbutaline’s fetal and neonatal effects, and hypokalemia is a maternal effect of β-agonists such as terbutaline, not a fetal risk of indomethacin.
Q3A 25-year-old woman at 29 weeks in preterm labor asks how long her tocolytic will be given and why.
Which statement describes the purpose of tocolysis?
- A.Preventive treatment in women at risk who are not in labor
- B.Continuing until 37 weeks so she can deliver at term
- C.A short delay of two to seven days to allow antenatal corticosteroids and transfer
- D.Long-term maintenance at home with oral terbutaline
Show answer
C. A short delay of two to seven days to allow antenatal corticosteroids and transfer — Tocolysis is intended to prolong gestation for two to seven days, providing a window for transfer, antenatal corticosteroids for fetal lung maturity and GBS prophylaxis; it is not intended to reach term. Tocolytics are not recommended as prophylaxis. Oral terbutaline is boxed against any tocolysis, and terbutaline should not be used for maintenance tocolysis at home.
Q4A 27-year-old woman at 30 weeks receives nifedipine for preterm labor. Thirty minutes later she is flushed and dizzy, with a blood pressure of 84/50 mm Hg.
What is the most likely mechanism?
- A.β2-receptor stimulation raising cAMP
- B.Oxytocin-receptor antagonism
- C.Cyclooxygenase inhibition reducing prostaglandins
- D.Calcium channel blockade causing vasodilation and hypotension
Show answer
D. Calcium channel blockade causing vasodilation and hypotension — Nifedipine blocks calcium entry to relax the myometrium, and it also has a hypotensive effect: flushing, headache, dizziness and hypotension are its maternal risks, and occasional patients have excessive, poorly tolerated hypotension. β2 stimulation is terbutaline’s mechanism, COX inhibition is indomethacin’s, and oxytocin-receptor antagonism belongs to atosiban and retosiban, which are not approved in the United States.
Sources
- Terbutaline sulfate injection (Hikma) — FDA label: boxed warning, contraindications, pharmacology, warnings, interactions — FDA / DailyMed
- Terbutaline sulfate tablets (Upsher-Smith) — FDA label: boxed warning against oral tocolysis — FDA / DailyMed
- Nifedipine capsules (Chartwell) — FDA label: indications, hypotension, CYP3A4 and grapefruit — FDA / DailyMed
- INDOCIN (indomethacin) oral suspension — FDA label: boxed warning, contraindications, fetal ductus and oligohydramnios — FDA / DailyMed
- Tocolysis — purpose, off-label status, mechanisms, agents — StatPearls (NCBI)
By LearnDrugs
Educational summary for medical students. Always verify against current prescribing information and guidelines. Not medical advice.