Tocolytic

Tocolytics (also called anti-contraction medications or labor suppressants) are medications used to suppress premature labor (from Greek τόκος tókos, "childbirth", and λύσις lúsis, "loosening"). 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.

Tocolytic
SpecialtyOB/GYN

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 (e.g., blood pressure monitoring when nifedipine is used as it reduces blood pressure; cardiotocography to assess fetal well-being). In any case, the risk of preterm labor alone justifies hospitalization.

Types of agents

There is no clear first-line tocolytic agent.[1][2]

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 (FDA) for use in stopping uterine contractions in preterm labor, instead being used off-label.

Drug Mechanism of action Description Possible
contraindications		 Maternal side effects Fetal and neonatal side effects
Terbutaline (Brethine) β2 agonist Off-label use, FDA has advised that injectable terbutaline should only be used in urgent situations, and that the oral form of the drug should never be used[3] Cardiac arrhythmias, diabetes Cardiac or cardiopulmonary arrhythmias, pulmonary edema, myocardial ischemia, hypertension, tachycardia, death Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia
Ritodrine (Yutopar) β2 agonist No longer FDA approved[4] Poorly controlled thyroid disease and diabetes Metabolic hyperglycemia, hyperinsulinemia, hypokalemia, antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinations Neonatal tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intraventricular hemorrhage
Fenoterol β2 agonist Diabetes
Salbutamol (INN) or albuterol (USAN) β2 agonist Diabetes
Hexoprenaline (Gynipral) β2 agonist Not FDA approved Hyperthyroidism, cardiovascular diseases, glaucoma, placental abruption, vaginal bleeding, inflammatory diseases of internal genitalia, 1st trimester of pregnancy, breastfeeding[5][6] Vertigo, anxiety, tremor, hyperhidrosis, tachycardia, hypotension, hyperglycemia, edema Hypoglycemia, bronchospasm, anaphylactic shock[6]
Nifedipine (Procardia, Adalat) Ca2+ channel blocker Is one of the most commonly used tocolytic agents.[7] Cardiac disease.[8] It should not be used concomitantly with magnesium sulfate Flushing, 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 collapse None noted as yet
Atosiban Oxytocin receptor antagonist Fewer side effects than β2 agonists
Indomethacin NSAID Late pregnancy (ductus arteriosus), significant renal or hepatic impairment Nausea, heartburn Constriction of ductus arteriosus, pulmonary hypertension, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis
Sulindac NSAID Coagulation disorders or thrombocytopenia, NSAID-sensitive asthma, other sensitivity to NSAIDs
Magnesium sulfate[9] Myosin light chain inhibitor Shown to be ineffective for delaying birth or stopping early birth.[9] Meta-analyses have failed to support it as a tocolytic agent[9][10][11] Absolute contraindication: myasthenia gravis. Use as a tocolytic agent may result in death of the fetus or infant.[9] Flushing, lethargy, headache, muscle weakness, diplopia, dry mouth, pulmonary edema, cardiac arrest Lethargy, hypotonia, respiratory depression, demineralization with prolonged use
Ethanol GABAA receptor PAM Shown to be ineffective. Was a frequently used tocolytic in the mid-20th century, but later double-blind studies[12] found it was not effective.

Calcium-channel blockers (such as nifedipine) and oxytocin antagonists (such as atosiban) may delay delivery by 2 to 7 days, depending on how quickly the medication is administered.[13] Otherwise, tocolysis is rarely successful beyond 24 to 48 hours because current medications do not alter the fundamentals of labor activation.[10] 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 (OR) of delivery within 24 hours of 0.54 (95% confidence interval (CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95% CI: 0.30-0.75).[1]

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.

See also

References
  1. Tan TC, Devendra K, Tan LK, Tan HK (May 2006). "Tocolytic treatment for the management of preterm labour: a systematic review". Singapore Med J. 47 (5): 361–6. PMID 16645683.
  2. de Heus R, Mol BW, Erwich JJ, et al. (2009). "Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study". BMJ. 338: b744. doi:10.1136/bmj.b744. PMC 2654772. PMID 19264820.
  3. Why do doctors still use terbutaline to delay preterm labor despite its major health risks? Retrieved on October 20th, 2020
  4. "Drugs@fda:fda approved drug products. (n.d.)".
  5. "Gynipral (hexoprenaline) Full Prescribing Information". Russian State Register of Medicinal Products (in Russian). Nycomed Austria GmbH. St. Peter-Straße 25, A-4020, Linz, Austria. Retrieved 19 March 2016.
  6. "Gynipral (hexoprenaline) Tablets 0.5 mg, Solution for Intravenous Infusion 5 μg/mL (0.0005%)". "RLS" (РЛС): Russian Register of Medical Products (in Russian). Retrieved 19 March 2016.
  7. Welcome to the Women's - The Royal Women's Hospital Victoria Australia
  8. "Nifedipine". The American Society of Health-System Pharmacists. Archived from the original on 25 December 2015. Retrieved 19 December 2015.
  9. Crowther, CA; Brown, J; McKinlay, CJ; Middleton, P (15 August 2014). "Magnesium sulphate for preventing preterm birth in threatened preterm labour". The Cochrane Database of Systematic Reviews (8): CD001060. doi:10.1002/14651858.CD001060.pub2. PMID 25126773.
  10. Simhan HN, Caritis SN (2007). "Prevention of Preterm Delivery". New England Journal of Medicine. 357 (5): 477–487. doi:10.1056/NEJMra050435. PMID 17671256.
  11. Nanda, K; Grimes, DA (2006). "Magnesium sulfate tocolysis: Time to quit". Obstetrics and Gynecology. 108 (4): 986–989. doi:10.1097/01.AOG.0000236445.18265.93. PMID 17012463. S2CID 30014199.
  12. Castrén O, Gummerus M, Saarikoski S (1975). "Treatment of imminent premature labour". Acta Obstet Gynecol Scand. 54 (2): 95–100. doi:10.3109/00016347509156739. PMID 1094787. S2CID 22685586.
  13. Iams JD, Romero R, Culhane JF, Goldenberg RL (2008). "Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth". The Lancet. 371 (9607): 164–175. doi:10.1016/S0140-6736(08)60108-7. PMID 18191687. S2CID 8204299.
  14. Wong, Perry, and Hockenberry. Maternal Child Nursing Care. Mosby 2002.
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