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| Cardiac tachyarrhythmias, poorly controlled [[diabetes mellitus]], hyperthyroidism, prolonged tocolysis(>48 to 72 hours)<ref>American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol. 2016 Oct;128(4):e155-64. doi: 10.1097/AOG.0000000000001711. PMID: 27661654.</ref>
| Cardiac tachyarrhythmias, poorly controlled [[diabetes mellitus]], hyperthyroidism, prolonged tocolysis(>48 to 72 hours)<ref>American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol. 2016 Oct;128(4):e155-64. doi: 10.1097/AOG.0000000000001711. PMID: 27661654.</ref>
| Tachycardia, palpitations, hypotension, dyspnea, chest pain, hypokalemia, hyperglycemia, lipolysis, pulmonary edema, myocardial ischemia <ref>Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm labor: a systematic review. Obstet Gynecol. 1999 Nov;94(5 Pt 2):869-77. doi: 10.1016/s0029-7844(99)00329-4. PMID: 10546776.</ref>
| Tachycardia, palpitations, hypotension, dyspnea, chest pain, hypokalemia, hyperglycemia, lipolysis, pulmonary edema, myocardial ischemia <ref>Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm labor: a systematic review. Obstet Gynecol. 1999 Nov;94(5 Pt 2):869-77. doi: 10.1016/s0029-7844(99)00329-4. PMID: 10546776.</ref>
| Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia<ref>{{Cite journal|last=Gaudet|first=Laura M.|last2=Singh|first2=Kavita|last3=Weeks|first3=Laura|last4=Skidmore|first4=Becky|last5=Tsertsvadze|first5=Alexander|last6=Ansari|first6=Mohammed T.|date=2012-02-21|title=Effectiveness of Terbutaline Pump for the Prevention of Preterm Birth. A Systematic Review and Meta-Analysis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3283660/|journal=PLoS ONE|volume=7|issue=2|doi=10.1371/journal.pone.0031679|issn=1932-6203|pmc=3283660|pmid=22363704}}</ref>
| Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia{{Citation needed|date=April 2017}}
|-
|-
| [[Ritodrine]] (Yutopar)
| [[Ritodrine]] (Yutopar)

Revision as of 21:54, 26 July 2021

Tocolytic
SpecialtyOB/GYN

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 their 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 (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 tachyarrhythmias, poorly controlled diabetes mellitus, hyperthyroidism, prolonged tocolysis(>48 to 72 hours)[4] Tachycardia, palpitations, hypotension, dyspnea, chest pain, hypokalemia, hyperglycemia, lipolysis, pulmonary edema, myocardial ischemia [5] Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia[6]
Ritodrine (Yutopar) β2 agonist No longer FDA approved[7] Poorly controlled thyroid disease and diabetes[citation needed] Metabolic hyperglycemia, hyperinsulinemia, hypokalemia, antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinations[citation needed] Neonatal tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intraventricular hemorrhage[citation needed]
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[8][9] Vertigo, anxiety, tremor, hyperhidrosis, tachycardia, hypotension, hyperglycemia, edema Hypoglycemia, bronchospasm, anaphylactic shock[9]
Nifedipine (Procardia, Adalat) Ca2+ channel blocker Is one of the most commonly used tocolytic agents.[10] Cardiac disease.[11] It should not be used concomitantly with magnesium sulfate[citation needed] 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[citation needed] None noted as yet[citation needed]
Atosiban Oxytocin receptor antagonist Fewer side effects than β2 agonists[citation needed]
Indomethacin NSAID Late pregnancy (ductus arteriosus), significant renal or hepatic impairment[citation needed] Nausea, heartburn[citation needed] Constriction of ductus arteriosus, pulmonary hypertension, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis[citation needed]
Sulindac NSAID Coagulation disorders or thrombocytopenia, NSAID-sensitive asthma, other sensitivity to NSAIDs[citation needed]
Magnesium sulfate[12] Myosin light chain inhibitor Shown to be ineffective for delaying birth or stopping early birth.[12] Meta-analyses have failed to support it as a tocolytic agent[12][13][14] Absolute contraindication: myasthenia gravis[citation needed]. Use as a tocolytic agent may result in death of the fetus or infant.[12] Flushing, lethargy, headache, muscle weakness, diplopia, dry mouth, pulmonary edema, cardiac arrest[citation needed] Lethargy, hypotonia, respiratory depression, demineralization with prolonged use[citation needed]
Ethanol GABAA receptor PAM Shown to be ineffective. Was a frequently used tocolytic in the mid-20th century, but later double-blind studies[15] 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.[16] Otherwise, tocolysis is rarely successful beyond 24 to 48 hours because current medications do not alter the fundamentals of labor activation.[13] 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,[citation needed] several general factors may contraindicate delaying childbirth with the use of tocolytic medications.

See also

References

  1. ^ a b 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. ^ American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 171: Management of Preterm Labor. Obstet Gynecol. 2016 Oct;128(4):e155-64. doi: 10.1097/AOG.0000000000001711. PMID: 27661654.
  5. ^ Gyetvai K, Hannah ME, Hodnett ED, Ohlsson A. Tocolytics for preterm labor: a systematic review. Obstet Gynecol. 1999 Nov;94(5 Pt 2):869-77. doi: 10.1016/s0029-7844(99)00329-4. PMID: 10546776.
  6. ^ Gaudet, Laura M.; Singh, Kavita; Weeks, Laura; Skidmore, Becky; Tsertsvadze, Alexander; Ansari, Mohammed T. (21 February 2012). "Effectiveness of Terbutaline Pump for the Prevention of Preterm Birth. A Systematic Review and Meta-Analysis". PLoS ONE. 7 (2). doi:10.1371/journal.pone.0031679. ISSN 1932-6203. PMC 3283660. PMID 22363704.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  7. ^ "Drugs@fda:fda approved drug products. (n.d.)".
  8. ^ "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.
  9. ^ a b "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.
  10. ^ Welcome to the Women's - The Royal Women's Hospital Victoria Australia
  11. ^ "Nifedipine". The American Society of Health-System Pharmacists. Archived from the original on 25 December 2015. Retrieved 19 December 2015.
  12. ^ a b c d 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.
  13. ^ a b Simhan HN, Caritis SN (2007). "Prevention of Preterm Delivery". New England Journal of Medicine. 357 (5): 477–487. doi:10.1056/NEJMra050435. PMID 17671256.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ a b c d e f g h i j k Wong, Perry, and Hockenberry. Maternal Child Nursing Care. Mosby 2002.
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