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a substance that exerts some force or effect
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any agent or representative of a federal agency or bureau (同)federal agent
a representative who acts on behalf of other persons or organizations
an active and efficient cause; capable of producing a certain effect; "their research uncovered new disease agents"
how long something has existed; "it was replaced because of its age"
a time of life (usually defined in years) at which some particular qualification or power arises; "she was now of school age"; "tall for his eld" (同)eld
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『代理人』;周旋人 / 働き(作用)を起こすもの;作用物,薬剤 / (政府機関,特にFBI,CIAなどの)部員,機関員
〈U〉(一般に)『年齢』,寿命;〈C〉(個々の)『年齢』,年 / 〈U〉成年(おとなとしての資格・権利を得る年齢;通例18または21歳) / 〈U〉『老齢』;《集合的に》老人たち / 〈U〉(人生の)『一時期』;〈C〉世代(generation) / 〈U〉〈C〉《しばしばA-》(歴史上の)『時代』 / 〈C〉《話》長い間 / 年をとる,ふける;〈物が〉古くなる / 〈年〉'を'とらせる;〈物〉'を'古びさせる

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/10 11:12:36」(JST)

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Tocolytics (also called anti-contraction medications or labor repressants) 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	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^[4] diabetes	Cardiac or cardiopulmonary arrhythmias, pulmonary edema, myocardial ischemia, hypertension, tachycardia, death ^[4]	Fetal tachycardia, hyperinsulinemia, hypoglycemia, myocardial and septal hypertrophy, myocardial ischemia ^[4]
Ritodrine (Yutopar)	β2-agonist	No longer FDA approved.^[5]	Poorly controlled thyroid disease and diabetes^[4]	Metabolic hyperglycemia, hyperinsulinemia, hypokalemia, antidiuresis, altered thyroid function, physiologic tremor, palpitations, nervousness, nausea or vomiting, fever, hallucinations ^[4]	Neonatal tachycardia, hypoglycemia, hypocalcemia, hyperbilirubinemia, hypotension, intraventricular hemorrhage ^[4]
Fenoterol	β2-agonist		diabetes
Salbutamol	β2-agonist		diabetes
Nifedipine (Procardia, Adalat)	CCBs	Is one of the most commonly used tocolytic agents.^[6]	Cardiac disease.^[4] It should not be used concomitantly with magnesium sulfate.^[4]	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.^[4]	None noted as yet^[4]
Atosiban	oxytocin antagonist	Less side effects than B2 recap agonist
Indomethacin	NSAIDs		late pregnancy (ductus arteriosus), significant renal or hepatic impairment ^[4]	Nausea, heartburn ^[4]	Constriction of ductus arteriosus, pulmonary hypertension, reversible decrease in renal function with oligohydramnios, intraventricular hemorrhage, hyperbilirubinemia, necrotizing enterocolitis ^[4]
Sulindac	NSAIDs		Coagulation disorders or thrombocytopenia, nonsteroidal anti-inflammatory drug (NSAID)-sensitive asthma, other sensitivity to NSAIDs^[4]
IV Magnesium sulfate^[7]	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.^[8]^[9]	Absolute contraindication: Myasthenia gravis^[4]	Flushing, lethargy, headache, muscle weakness, diplopia, dry mouth, pulmonary edema, cardiac arrest ^[4]	Lethargy, hypotonia, respiratory depression, demineralization with prolonged use ^[4]
Ethyl alcohol	?	Shown to be ineffective. Was frequently prescribed as a tocolytic in the mid-20th century, but later double-blind studies^[10] found it was not effective.

Calcium-channel blockers and an oxytocin antagonist can delay delivery by 2–7 days.^[11] Otherwise, tocolysis is rarely successful beyond 24–48 hours because current medication do not alter the fundamentals of labor activation.^[8] 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 tocolysis

In addition to drug-specific contraindications,^[4] several general factors may contraindicate delaying birth with the use of tocolytic medications.

Fetus is older than 34 weeks gestation ^[12]
Fetus weighs less than 2500 grams or has intrauterine growth restriction (IUGR)^[12] or placental insufficiency^[4]
Lethal congenital or chromosomal abnormalities^[4]^[12]
Cervical dilation is greater than 4 centimeters^[12]
Chorioamnionitis or intrauterine infection is present^[4]^[12]
Mother has severe pregnancy-induced hypertension,^[12] eclampsia^[12]/preeclampsia,^[4] active vaginal bleeding,^[12] placental abruption,^[4] a cardiac disease,^[12] or another condition which indicates that the pregnancy should not continue.^[12]
Other cause of fetal distress or fetal death^[12]

References

^ ^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.
^ 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.
^ ^a ^b Healthline > Treatment of Preterm Labor: Tocolytics Health Article Retrieved on 6 January 2009
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w Management of preterm labor. American College of Obstetricians and Gynecologists (ACOG). Management of preterm labor. Washington (DC): 2003 May. 9 p. (ACOG practice bulletin; no. 43).
^ [<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"].
^ 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. doi:10.1002/14651858.CD001060. PMID 12519550.
^ ^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.
^ 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.
^ 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. doi:10.1016/S0140-6736(08)60108-7. PMID 18191687.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k Wong, Perry, and Hockenberry. Maternal Child Nursing Care. Mosby 2002

UpToDate Contents

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1. 切迫早産の予防 inhibition of acute preterm labor
2. 硫酸マグネシウムへの子宮内曝露の神経保護効果 neuroprotective effects of in utero exposure to magnesium sulfate
3. 切迫早産予防後の妊婦のマネージメント management of pregnant women after inhibition of acute preterm labor
4. 妊娠中および周産期における急性呼吸不全 acute respiratory failure during pregnancy and the peripartum period
5. 非産科手術を受けた妊娠患者のマネージメント management of the pregnant patient undergoing nonobstetric surgery

English Journal

Setting research priorities to improve global newborn health and prevent stillbirths by 2025.

Yoshida S1, Martines J2, Lawn JE3, Wall S4, Souza JP5, Rudan I6, Cousens S7; neonatal health research priority setting group, Aaby P8, Adam I9, Adhikari RK10, Ambalavanan N11, Arifeen SE12, Aryal DR13, Asiruddin S14, Baqui A15, Barros AJ16, Benn CS17, Bhandari V18, Bhatnagar S19, Bhattacharya S20, Bhutta ZA21, Black RE22, Blencowe H23, Bose C24, Brown J25, Bührer C26, Carlo W27, Cecatti JG28, Cheung PY29, Clark R30, Colbourn T31, Conde-Agudelo A32, Corbett E33, Czeizel AE34, Das A35, Day LT36, Deal C37, Deorari A38, Dilmen U39, English M40, Engmann C41, Esamai F42, Fall C43, Ferriero DM44, Gisore P45, Hazir T46, Higgins RD47, Homer CS48, Hoque DE12, Irgens L49, Islam MT50, de Graft-Johnson J51, Joshua MA52, Keenan W53, Khatoon S54, Kieler H55, Kramer MS56, Lackritz EM57, Lavender T58, Lawintono L59, Luhanga R60, Marsh D51, McMillan D61, McNamara PJ62, Mol BW63, Molyneux E64, Mukasa GK65, Mutabazi M66, Nacul LC67, Nakakeeto M68, Narayanan I69, Olusanya B70, Osrin D71, Paul V38, Poets C72, Reddy UM73, Santosham M74, Sayed R75, Schlabritz-Loutsevitch NE76, Singhal N77, Smith MA78, Smith PG79, Soofi S80, Spong CY81, Sultana S82, Tshefu A83, van Bel F84, Gray LV85, Waiswa P86, Wang W87, Williams SL88, Wright L73, Zaidi A89, Zhang Y90, Zhong N91, Zuniga I92, Bahl R1.
Journal of global health.J Glob Health.2016 Jun;6(1):010508. doi: 10.7189/jogh.06.010508.
BACKGROUND: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline f
PMID 26401272

Effectiveness of Tocolytic Agents on Prevention of Preterm Delivery, Neonatal Morbidity, and Mortality: Is There a Consensus? A Review of the Literature.

Petousis S1, Margioula-Siarkou C1, Kalogiannidis I2.
Obstetrical & gynecological survey.Obstet Gynecol Surv.2016 Apr;71(4):243-52. doi: 10.1097/OGX.0000000000000302.
Preterm delivery presents the main cause of neonatal morbidity and mortality worldwide. The rate of preterm delivery is 12% to 13% in the United States, of which 29% concerns preterm deliveries before 34 weeks of gestation. Basic parameter of prevention strategy is implementation of tocolytic therap
PMID 27065070

Genotoxic effect of tocolytic drug ritodrine in combination with smoking during pregnancy.

Kareli D1, Pouliliou S2, Liberis A3, Nikas I3, Psillaki A3, Kontomanolis E3, Nikolettos N4, Galazios G3, Lialiaris T1.
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.J Matern Fetal Neonatal Med.2016 Mar 18:1-10. [Epub ahead of print]
OBJECTIVE: Tocolytic drugs are used widely in order to prevent preterm birth. Ritodrine, is the only food and drug administration (FDA) approved drug for tocolytic use. We estimated the cytogenetic effect of ritodrine administered as maternal therapy, alone or in combination with smoking, in women a
PMID 26742485

Japanese Journal

4)硫酸マグネシウムを使用する立場に立って : 硫酸マグネシウム短期単剤療法の効果((2)切迫早産の治療,4)周産期,クリニカルディベート,第63回日本産科婦人科学会学術講演会講演要旨,研修コーナー)

日本産科婦人科學會雜誌 64(1), "N-21"-"N-25", 2012-01-01
NAID 110008913817

Investigation of β_2-adrenoceptor subtype selectivity and organ specificity for bedoradrine (KUR-1246), a novel tocolytic beta-adrenergic receptor stimulant