Tocolytic
Tocolytics (also called anti-contraction medications or labor suppressants) are medications used to suppress premature labor (from the Greek tokos, childbirth, and lytic, capable of dissolving). They are given when delivery would result in premature birth. The therapy also buys time for the administration of betamethasone, a glucocorticoid drug which greatly accelerates fetal lung maturity, but takes one to two days to work.
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, as for instance blood pressure monitoring when nifedipine is used as it reduces blood pressure. 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 | Is often the drug given first, especially if there is only low risk of preterm birth.[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. 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[8] | Myosin light chain inhibitor | Shown to be ineffective. Has been recommended for women at high risk.[3] However, meta-analyses have failed to support it as a tocolytic agent[9][10] | Absolute contraindication: myasthenia gravis | 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[11] found it was not effective. |
Calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days.[12] Otherwise, tocolysis is rarely successful beyond 24–48 hours because current medication do not alter the fundamentals of labor activation.[9] However, just gaining 48 hours is sufficient to allow the pregnant women to be transferred to a center specialized for management of preterm deliveries and give administered corticosteroids the possibility to reduce neonatal organ immaturity.
The efficacy of beta-agonists, atosiban and indomethacin is a decreased odds ratio (OR) of delivery within 24 hours of 0.54 (95 percent confidence interval (CI): 0.32-0.91) and 0.47 within 48 hours (OR 0.47, 95 percent CI 0.30-0.75).[1]
Antibiotics may 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 birth with the use of tocolytic medications.
- Fetus is older than 34 weeks gestation[13]
- Fetus weighs less than 2500 grams or has intrauterine growth restriction (IUGR)[13] or placental insufficiency
- Lethal congenital or chromosomal abnormalities[13]
- Cervical dilation is greater than 4 centimeters[13]
- Chorioamnionitis or intrauterine infection is present[13]
- Mother has severe pregnancy-induced hypertension,[13] eclampsia[13]/preeclampsia, active vaginal bleeding,[13] placental abruption, a cardiac disease,[13] or another condition which indicates that the pregnancy should not continue.[13]
- Other cause of fetal distress or fetal death[13]
See also
References
- 1 2 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.
- ↑ 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. PMC 2654772
. PMID 19264820. doi:10.1136/bmj.b744. - 1 2 Healthline > Treatment of Preterm Labor: Tocolytics Health Article Retrieved on 6 January 2009
- ↑ [<Drugs@fda:fda approved drug products. (n.d.). Retrieved from http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=RITODRINE HCL> "Drugs@FDA"] Check
|url=value (help). - ↑ "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.
- 1 2 "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.
- ↑ Welcome to the Women's - The Royal Women's Hospital Victoria Australia
- ↑ Crowther CA, Hiller JE, Doyle LW (2002). Crowther, Caroline A, ed. "Magnesium sulphate for preventing preterm birth in threatened preterm labour". Cochrane Database Syst Rev (4): CD001060. PMID 12519550. doi:10.1002/14651858.CD001060.
- 1 2 Simhan HN, Caritis SN (2007). "Prevention of Preterm Delivery". New England Journal of Medicine. 357 (5): 477–487. PMID 17671256. doi:10.1056/NEJMra050435.
- ↑ Nanda, K; Grimes, DA (2006). "Magnesium sulfate tocolysis: Time to quit". Obstetrics and Gynecology. 108 (4): 986–989. PMID 17012463. doi:10.1097/01.AOG.0000236445.18265.93.
- ↑ Castrén O, Gummerus M, Saarikoski S (1975). "Treatment of imminent premature labour". Acta Obstet Gynecol Scand. 54 (2): 95–100. PMID 1094787.
- ↑ 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. PMID 18191687. doi:10.1016/S0140-6736(08)60108-7.
- 1 2 3 4 5 6 7 8 9 10 11 Wong, Perry, and Hockenberry. Maternal Child Nursing Care. Mosby 2002