Tocolytic


Tocolytics are medications used to suppress premature labor. Tocolytic therapy is provided when delivery would result in premature birth, postponing delivery long enough for the administration of glucocorticoids, which accelerate fetal lung maturity but may take one to two days before its effects are seen.
The suppression of contractions is often only partial and tocolytics can only be relied on to delay birth for several days. Depending on the tocolytic used the mother or fetus may require monitoring. In any case, the risk of preterm labor alone justifies hospitalization.

Types of agents

There is no clear first-line tocolytic agent.
Various types of agents are used, with varying success rates and side effects. Some medications are not specifically approved by the U.S. Food and Drug Administration for use in stopping uterine contractions in preterm labor, instead being used off-label.
DrugMechanism of actionDescriptionPossible
contraindications		Maternal side effectsFetal and neonatal side effects
Terbutaline β2 agonistIs often the drug given first, especially if there is only low risk of preterm birth.Cardiac arrhythmias, diabetesCardiac or cardiopulmonary arrhythmias, pulmonary edema, myocardial ischemia, hypertension, tachycardia, deathFetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia
Ritodrine β2 agonistNo longer FDA approvedPoorly controlled thyroid disease and diabetesMetabolic hyperglycemia, hyperinsulinemia, hypokalemia, antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinationsNeonatal tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intraventricular hemorrhage
Fenoterolβ2 agonistDiabetes
Salbutamol or albuterol β2 agonistDiabetes
Hexoprenaline β2 agonistNot FDA approvedHyperthyroidism, cardiovascular diseases, glaucoma, placental abruption, vaginal bleeding, inflammatory diseases of internal genitalia, 1st trimester of pregnancy, breastfeedingVertigo, anxiety, tremor, hyperhidrosis, tachycardia, hypotension, hyperglycemia, edemaHypoglycemia, bronchospasm, anaphylactic shock
Nifedipine Ca2+ channel blockerIs one of the most commonly used tocolytic agents.Cardiac disease. It should not be used concomitantly with magnesium sulfateFlushing, headache, dizziness, nausea, transient hypotension. Administration of calcium channel blockers should be used with care in patients with renal disease and hypotension. Concomitant use of calcium channel blockers and magnesium sulfate may result in cardiovascular collapseNone noted as yet
AtosibanOxytocin receptor antagonistFewer side effects than β2 agonists
IndomethacinNSAIDLate pregnancy, significant renal or hepatic impairmentNausea, heartburnConstriction of ductus arteriosus, pulmonary hypertension, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis
SulindacNSAIDCoagulation disorders or thrombocytopenia, NSAID-sensitive asthma, other sensitivity to NSAIDs
Magnesium sulfateMyosin light chain inhibitorShown to be ineffective for delaying birth or stopping early birth. Meta-analyses have failed to support it as a tocolytic agentAbsolute contraindication: myasthenia gravis. Use as a tocolytic agent may result in death of the fetus or infant.Flushing, lethargy, headache, muscle weakness, diplopia, dry mouth, pulmonary edema, cardiac arrestLethargy, hypotonia, respiratory depression, demineralization with prolonged use
EthanolGABAA receptor PAMShown to be ineffective. Was a frequently used tocolytic in the mid-20th century, but later double-blind studies found it was not effective.

Calcium-channel blockers and oxytocin antagonists may delay delivery by 2 to 7 days, depending on how quickly the medication is administered. Otherwise, tocolysis is rarely successful beyond 24 to 48 hours because current medications do not alter the fundamentals of labor activation. However, postponing premature delivery by 48 hours appears sufficient to allow pregnant women to be transferred to a center specialized for management of preterm deliveries, and thus give administered corticosteroids the possibility to reduce neonatal organ immaturity.
The efficacy of β-adrenergic agonists, atosiban, and indomethacin is a decreased odds ratio of delivery within 24 hours of 0.54 and 0.47 within 48 hours.
Antibiotics may also delay the onset of labor in women with premature rupture of membranes, but this is not usually characterized as tocolysis.

Contraindications to tocolytics

In addition to drug-specific contraindications, several general factors may contraindicate delaying childbirth with the use of tocolytic medications.