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Side effects of tocolytics

Beta-Adrenergic receptor-agonists (Terbutaline)

Ritodrine is the only FDA approved medication in this class, but (ironically) isn’t available in the US. Thus, terbutaline is frequently used for this indication. Beta-agonists relax smooth muscles, including the myometrium. Binding of the receptor increases intracellular levels of cyclic AMP. This increase in intracellular levels of cyclic AMP activates protein kinase, which inactivates myosin light-chain kinase, and decreases myometrium contractility.

Side effects: Tachycardia, hypotension, palpitations, shortness of breath, chest pain, pulmonary edema, hypokalemia, hyperglycemia. Contraindications include tachycardia-sensitive maternal cardiac conditions.

Magnesium Sulfate

The mechanism not completely understood, but likely works by decreasing the availability of calcium by blocking membrane and intracellular calcium channels, decreasing contractility.

Side effects: Hypotension, can potentiate the action of depolarizing and non-depolarizing muscle relaxants, pulmonary edema, nausea, flushing, headache, lethargy. Myasthenia Gravis is a contraindication to the use of magnesium sulfate.

Nitric Oxide Donors (nitroglycerin)

Nitroglycerin increases intracellular levels of cyclic GMP leading to inactivation of myosin light-chain kinase, and relaxation of smooth muscle.

Side effects: Flushing, tachycardia, hypotension and headache. There are no real contraindications, but preload dependent cardiac lesions will likely worsen with nitroglycerin.

Calcium Channel Blockers (Nifedipine)

Nifedipine directly inhibits the influx of calcium into the cell membrane and the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium levels leads to an inhibition of myosin light-chain kinase, and relaxes the myometrium.

Side effects: Dizziness, flushing, hypotension. When used with magnesium sulfate: suppression of heart rate, decreased contractility, elevation of hepatic enzyme levels.

Cyclooxygenase Inhibitors (Indomethacin)

Prostaglandin increases intracellular calcium levels, and release from the sarcoplasmic reticulum. COX inhibitors inhibit this release and cause relaxation of the myometrium.

Side Effects: Nausea, GERD, gastritis, platelet dysfunction.

Oxytocin-receptor antagonists

Oxytocin leads to increased intracellular calcium levels and uterine contractions. Oxytocin-receptor antagonists compete with oxytocin at the receptor level, and decrease levels of intracellular calcium.

Side Effects: Hypersensitivity reactions, injection-site reactions. Atosiban was shown to increase the rate of fetal or infant death in a randomized, double-blinded study.


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  2. J M Moutquin, D Sherman, H Cohen, P T Mohide, D Hochner-Celnikier, M Fejgin, R M Liston, J Dansereau, M Mazor, E Shalev, M Boucher, M Glezerman, E Z Zimmer, J Rabinovici Double-blind, randomized, controlled trial of atosiban and ritodrine in the treatment of preterm labor: a multicenter effectiveness and safety study. Am. J. Obstet. Gynecol.: 2000, 182(5);1191-9 PubMed Link