Current pharmacotherapy options for labor induction

Introduction: Labor induction is now reported to occur in up to 30 – 40% of obstetrical patients. There are a number of pharmacological options available to facilitate labor induction, including oxytocin and analogues of prostaglandins E1 and E2, which have particular utility when labor induction necessitates cervical ripening, as when labor induction occurs in the context of an unfavorable cervix.

Areas covered: This paper reviews acceptable pharmacological options for labor induction, especially when cervical ripening is required. These options include oxytocin and a number of prostaglandin formulations using dinoprostone and misoprostol. It also covers several analyses of published clinical trials (Phase-III) describing evidence of effectiveness.

Expert opinion: Oxytocin is best used when labor needs to be induced in the context of a favorable cervix. When the cervix is not favorable, cervical ripening using prostaglandins should precede labor induction. Either dinoprostone or misoprostol are superior to oxytocin alone for cervical ripening. However, judicious, careful considerations need to be made at the outset of labor induction so as to balance maternal and fetal risks, and these should be guided by institutional policies that reflect the evidence-base.     

Pharmacotherapy options for labor induction

Introduction: Induction of labor remains one of the most commonly performed procedures in the US and in other developed countries around the world. Various agents for cervical ripening are used prior to induction; the most commonly used are prostaglandins and oxytocin. The ideal agent is one that decreases time to vaginal delivery without compromising maternal and/or fetal safety.

Areas covered: This article reviews the current pharmacologic methods available for induction of labor. Although these agents have been extensively studied and their safety and efficacy profile are well accepted, there is still ongoing research to determine the safest and most effective method. The article discusses the impact of pharmacogenomics as it relates to the most common induction agents. The dosing, route of administration, and side effects of these agents are reviewed.

Expert opinion: Prostaglandins and oxytocin have been proven to be safe and effective methods of induction. However, the optimal medication for induction is yet to be determined. Although there are currently no pharmacogenomic findings that affect dosing of either prostaglandins or oxytocin, this is a growing area of research. In the near future, it may become clear that there is no ‘one regimen for all’ when selecting an induction or cervical ripening agent, or any other pharmaceutical altogether.     

A randomised controlled trial f an oral solution of prostaglandin E2 and oral oxytocin used immediately after low amniotomy for induction of Iabour in the presence of a favourable cervix

Summary

A randomised controlled trial was carried out in 50 primigravidae and 50 multi-gravidae to compare the effectiveness in induction of labour after low amniotomy of prostaglandin E₂, given as an oral solution, and oxytocin, given as buccal tablets. The results showed that in dosages recommended by the manufacturers, both oxytocic preparations were almost equally effective. With oral oxytocin, once labour had been established and dosage was left to the discretion of the staff, there appeared to be a potentially dangerous tendency to continue giving large doses despite adequate uterine contractions. The authors comment that this was probably the reason why oxytocin-treated multigravidae having normal deliveries within 24 hours had labours significantly shorter on average than those of other successfully induced patients.     

比较米索前列醇与缩宫素足月引产的疗效

目的：比较阴道给米索前列醇与静脉滴注缩宫素对足月引产的有效性及安全性。方法：５０例产妇（初产妇４９例、经产妇１例）年龄２０～４０ａ，妊娠３７．６～４２．４ｗｋ，随机分为２组，各２５例。Ａ组用米索前列醇１片（５０μｇ／片）阴道给药，４～６ｈ重复直至临产。Ｂ组用静脉滴注缩宫素２．５～５ＩＵ。结果：用药后６ｈＡ组比Ｂ组宫颈Ｂｉｓｈｏｐ评分改善更明显（Ｐ＜０．０５）；从给药引产到阴道分娩的时间短，但无统计学差异（１１±５ｈｖｓ１５±７ｈ，Ｐ＞０．０５）；引产成功率高（８８％ｖｓ４４％，Ｐ＜０．０１）；２组均未发现明显副作用。结论：阴道给米索前列醇较静脉滴注缩宫素足月引产的成功率高。     

小剂量米索前列醇用于足月妊娠引产

目的 :观察采用小剂量 (33.3μg)米索前列醇用于足月妊娠引产的有效性和安全性。方法 :米索前列醇组 :有引产指征、无引产及使用米索前列醇禁忌证的单胎、头位、胎膜完整的足月妊娠妇女 31例 ,采用小剂量 (33.3μg)米索前列醇阴道给药引产。间隔 4～ 6h重复给药 ,2 4h内最大剂量为 2 0 0μg。缩宫素组 :同条件足月妇娠妇女 2 8例 ,采用小剂量缩宫素 (5%葡萄糖氯化钠注射液 50 0mL +缩宫素 2 .5IU)静脉滴注引产。结果 :米索前列醇组和缩宫素组引产成功率分别为 81%和 57% ,差异有显著意义 ,P <0 .0 5。首次用药到临产时间分别为 14h±s 13h和 2 7h± 16h ,差异有显著意义 ,P <0 .0 5。产程时间、分娩方式、产后出血量 2组比较 ,P>0 .0 5,差异均无显著意义。结论 :小剂量 (33.3μg)米索前列醇用于足月妊娠引产是有效且安全的方法 ,其引产成功率和缩短引产时间方面优于小剂量缩宫素静脉滴注引产。     

过期妊娠用缩宫素引产失败后用卡前列甲酯栓的疗效

目的：观察足月妊娠用缩宫素引产失败后再用卡前列甲酯栓的疗效。方法：４６例孕妇，妊娠４１．２±ｓ１．３ｗｋ，年龄２５±ｓ５ａ，无前列腺素药物禁忌证，在用缩宫素引产失败后１０～１２ｈ内，于阴道后穹窿放置卡前列甲酯栓０．３ｍｇ，平卧３０ｍｉｎ，２４ｈ无宫缩再放０．３ｍｇ。结果：４６例中１次用药引产成功３６例，２次用药引产成功１０例，成功率１００％。与同期缩宫素引产成功的８６例相比，诱发宫缩的时间明显缩短，Ｐ＜０．０５。但分娩方式，新生儿出生１ｍｉｎＡｐｇａｒ评分及产后出血量，两者皆无显著差异，Ｐ＞０．０５。结论：缩宫素引产失败后，再用卡前列甲酯栓，效果满意。     

A comparison between intravenous oxytocin and oral prostaglandin E2 for the induction of labour in parous patients

Summary

A prospective survey was carried out on 187 parous patients, in whom labour was induced by amniotomy and either intravenous oxytocin or oral prostaglandin E₂, (PGE₂).

The results show no significant difference in the performance of each group for the induction to delivery interval, the mode of delivery, the Apgar score at 5 minutes or for third stage anomalies.

The use of oral PGE₂offers advantages to the patient who is spared the discomfort, restriction and minor risks associated with an intravenous infusion; and to the midwife who does not have to make frequent checks on the flow rate if an infusion pump is not available. The method also permits the ancillary equipment, which may well be in limited supply, to be reserved for more ‘at risk’ cases.     

米索前列醇与催产素在晚孕引产中的比较

目的 观察米索前列醇晚孕引产的效果及其临床特点。方法将１００例有引产指征的晚孕、单胎、头位无宫缩的初产妇,随机分为两组,研究组６０例,用米索胶列醇５０μｇ置阴道后穹窿,每４ｈ用药一次至有宫缩止。对照组４０例,用０．５％的催产素静滴引产。结果研究组引产成功率为９５％,明显高于对照组的７５％,用药至临产时间前为４．１７ｈ,后为８．３８ｈ,尤其是对宫颈评分≤５分,研究组优于对照组,月外,米索前列     

缩宫素和米索前列醇用于足月引产疗效观察

目的探讨小剂量缩宫素静点和小剂量米索前列醇片阴道放置用于足月妊娠引产的疗效及对母儿的影响。方法180例孕妇静滴缩宫素，200例孕妇米索前列醇片50p,g阴道后穹隆放置，条件相同、单胎头位、孕37～43周之间孕妇进行引产。结果缩宫素组和米索前列醇组的引产成功率，产程停滞、宫缩过强、剖宫产发生率差异有统计学意义。新生儿窒息、产时感染、羊水污染、胎心异常、新生儿出生评分、体重差异均无统计学意义。结论小剂量米索前列醇用于足月妊娠引产成功率高，促宫颈成熟时间短，效果优于缩宫素。     

前列腺素E2栓与缩宫素用于妊娠期糖尿病引产的对比分析

目的探讨妊娠期糖尿病采用前列腺素E2栓与缩宫素引产的效果对比。方法本次研究选择的对象共80例,均为本院2010年6月-2012年8月收治的妊娠期糖尿病行引产术者,随机按观察组和对照组各40例划分,对照组采用缩宫素治疗,观察组采用前列腺素E2栓治疗,回顾两组临床资料。结果两组用药前Bishop评分差异无统计学意义（P〉0．05）,用药后12h观察组显著高于对照组,差异有统计学意义（P〈0．05）。观察组临产时间短于对照组,阴道顺产率高于对照组,产后出血量及出生5min新生儿Apgar评分无明显差异（P〉0．05）。结论妊娠糖尿病患者引产中应用前列腺素E2栓药物,可缩短临产时间、促进宫颈成熟和引产,降低剖宫产率,为母婴安全提供了保障。     

Pharmacological,conformational and dynamic properties of cycloleucine-2 analogues of oxytocin and [1-penicillamine]oxytocin

The solid phase syntheses of [2-cycloleucine]oxytocin and [1-penicillamine, 2-cycloleucine]oxytocin are reported. [1-Penicillamine, 2-cycloleucine]oxytocin is an oxytocin antagonist exhibiting no in vitro oxytocic activity. In the in vitro oxytocic assay, [1-penicillamine, 2-cycloleucine]oxytocin has a pA₂ value of 6.70 ± 0.08. [2-Cycloleucine]-oxytocin is a full oxytocin agonist exhibiting 4.9 ± 0.5 U/mg of oxytocic activity. Neither compound possesses any measurable agonist or antagonist activity in the rat pressor assay. Carbon-13 nuclear magnetic resonance chemical shift parameters and spin-lattice relaxation times (T₁) of the antagonist, [1-penicillamine, 2-cycloleucine]oxytocin, indicate that the antagonist exhibits similar conformational and dynamic properties as other oxytocin inhibitors previously studied. The carbon-13 nuclear magnetic resonance shift parameters and spin-lattice relaxation times (T₁) of the oxytocin agonist, [2-cycloleucine] oxytocin, indicate that the agonist exhibits similar conformational and dynamic properties as oxytocin. These results are discussed in terms of the different receptor requirements for agonist and antagonist activities. It appears that there are different structural and conformational requirements at the 2-position for oxytocic agonist and antagonist activities.     

地诺前列酮与缩宫素用于足月妊娠引产效果的临床观察

目的：观察分析地诺前列酮与缩宫素用于足月妊娠引产效果的临床效果和安全性。方法选取108例足月妊娠引产产妇,随机分为观察组和对照组,各54例。分别给予地诺前列酮和缩宫素引产。观察比较两组的引产效果。结果在宫颈Bishop评分、12 h临产率、24 h临产率、总有效率、阴道分娩率方面比较,观察组明显优于对照组,差异有统计学意义。在不良反应、新生儿结局方面比较,差异无统计学意义。结论地诺前列酮用于足月妊娠引产效果的临床效果较好,安全性较高,值得推广。     

妊娠中期引产228例临床效果分析

目的:探讨米非司酮配伍米索前列醇用于妊娠中期引产的临床效果.方法:对2008年1月～2010年12月来我院就诊妊娠12～24周要求引产者228例,按不同引产方式进行分组,药物组(140例)及利凡诺组(88例),对两组引产效果进行分析.药物组根据米索前列醇不同给药方式分为口服组及直肠给药组,比较引产时间及用药剂量.结果:药物组与利凡诺组胎盘胎膜残留、引产时间及出血量比较差异有显著性(P＜0.05);妊娠12～16周,口服组与直肠给药组引产时间比较差异有显著性(P＜0.05);妊娠16～24周,口服组与直肠给药组米索前列醇用量比较差异有显著性(P＜0.05).结论:米非司酮配伍米索前列醇用于中期引产具有成功率高、完全流产率高、引产时间短及阴道流血量少等优点,根据孕周不同,选择合适米索前列醇的给药方式可提高引产效率,减轻患者痛苦.     

地诺前列酮与缩宫素用于足月妊娠引产效果的临床观察

目的：探讨地诺前列酮用于足月妊娠促宫颈成熟及引产的有效性及安全性。方法：选择220例足月妊娠单胎头位、无引产禁忌的初产妇和经产妇,采用双盲对照研究的方法随机分为两组,观察组110例采用阴道后穹隆放置地诺前列酮1枚引产,对照组110例以缩宫素静滴引产,对两组宫颈成熟Bishop评分,对产程的影响,引产成功率,阴道分娩率及对胎儿和新生儿的影响进行比较。结果：观察组促宫颈成熟效果明显优于对照组（P〈0.01）;用药至临产的时间观察组显著短于对照组（P〈0.01）;观察组12h临产率为67.3%,24h临产率为87.3%,对照组12h临产率为46.4%,24h临产率为70.0%,两组比较,差异有统计学意义（P〈0.01）;观察组引产成功率高于对照组,观察组阴道分娩率为65.5%,对照阴道分娩率为51.8%,两组差异有统计学意义（P〈0.05）;对母婴的影响两组差异无统计学意义。结论：地诺前列酮用于初产妇和经产妇的促宫颈成熟及诱发宫缩作用优于缩宫素,它可以显著提高宫颈Bishop评分,从而提高阴道分娩率,促进自然分娩,临床应用简便、安全、有效,值得产科临床推广使用。     

Effective Stereoselective Total Synthesis of 16,16-Dimethyl Prostaglandin E2

The first stereoselective synthesis of the specific EP₁ receptor agonist, 16,16-dimethyl prostaglandin E₂ 1 , is described. The key intermediate 3 was obtained from the E-allyl alcohol 6 via Sharpless epoxidation followed by stereospecific transformations to the γ-iodo vinyl compound 3 . Two component coupling of 2 and 3 , using the dilithiocyanocuprate technology, gave the 1,4-addition product. Mild desilylation and enzymatic ester cleavage produced the optically pure prostaglandin 1 in high yield.     

依沙吖啶联合米非司酮治疗中期妊娠引产的临床研究

目的 探讨依沙吖啶联合米非司酮在中期妊娠引产治疗中的临床疗效。方法 选取郑州大学第三附属医院2015年1月-2019年6月产科220例中期妊娠引产患者为研究对象。根据治疗方法将患者分为对照组（80例）和观察组（140例）。对照组先口服米非司酮片,50 mg/次,2次/d,连续服用2 d后将米索前列醇片置于阴道穹窿处,妊娠24周以内400 μg/次,3 h重复,但不超过1.8 mg;妊娠24周以上200 μg/次,6 h可重复,每日给药不超过4次。观察组患者口服米非司酮片（用法同对照组）后1 h采用7号穿刺针于下腹正中、宫底下两三横指下方腹中线上进行羊膜腔穿刺,注入100 mg乳酸依沙吖啶注射液。比较两组患者的引产效果、手术情况、疼痛程度、月经恢复以及不良反应发生情况。结果 治疗后,观察组患者引产成功率与清宫率分别为98.57%与19.29%,对照组患者引产成功率与清宫率分别为85.00%与35.00%,两组比较存在统计学差异（P<0.05）。与对照组相比,观察组患者的产后2 h出血量、用药至规律宫缩时间、规律宫缩至胎儿娩出时间、产后出血时间及胎盘残留率更少（P<0.05）。治疗后,观察组患者1分疼痛的比率显著高于对照组（P<0.05）。两组患者月经复潮时间及经期持续时间比较无统计学差异。治疗期间,观察组和对照组不良反应发生率分别为8.57%、17.50%,两组比较无统计学差异。结论 依沙吖啶联合米非司酮可有效提高引产效果,引产时间短,产后恢复快,安全性高,在中期妊娠引产患者中具有较高的应用价值。     

益母草胶囊联合利凡诺应用于中期引产的价值评价

目的 探讨益母草胶囊联合利凡诺注射液在中期妊娠引产中临床治疗效果.方法 中期妊娠引产患者共200例,随机数字表法分为观察组和对照组,其中观察组110例,对照组90例.观察组采用利凡诺羊膜腔内注射引产,术后给予益母草胶囊口服;对照组采用米非司酮和米索前列醇引产,比较两组患者终止妊娠时间、阴道出血量、胎盘残留量、不良反应发生率.结果 观察组终止妊娠时间为(28.2±5.3)h,显著短于对照组的终止妊娠时间(33.4±6.8)h,差异有统计学意义(P＜0.01);观察组患者阴道出血量为(113.5±37.4) ml,明显小于对照组患者阴道出血量(159.3±49.2) ml,差异有统计学意义(P＜ 0.01);观察组胎盘残留量(23.6±11.4)g,显著少于对照组胎盘残留量(27.6±12.7)g,差异有统计学意义(P＜0.05);观察组VAS评分(6.2±2.7)分,明显小于对照组VAS评分(7.2±3.1)分,差异有统计学意义(P＜0.05).观察组发生恶心呕吐2例,皮疹、瘙痒2例,不良反应发生率为3.6％;对照组发生恶心呕吐4例,皮肤瘙痒6例,不良反应发生率为11.1％,组间比较差异具有统计学意义(P＜0.05).结论 益母草胶囊联合利凡诺用于中期妊娠引产疗效确切,同时具有不良反应发生率低等优点,值得临床推广应用.     

乳房按摩及心理诱导对促进产程进展的临床研究

目的 探讨乳房按摩及心理诱导对促进初产妇产程进展和分娩结果的影响.方法 选择无头盆不称、妊娠合并症和并发症的300例初产妇,随机分为观察组和对照组1、2,每组各100例进行比较观察.对照组1按常规护理及健康宣教,并给予静脉点滴催产素加强宫缩;对照组2按常规护理及健康宣教,正常的产程观察;而观察组除常规护理及健康宣教外给予乳头按摩及心理诱导.结果 观察组剖宫产率为4％、总产程时间平均值为5.93 h、产后2 h出血平均值为222.78 ml、新生儿窒息发生率为2％均明显低于对照组(P＜0.01或P＜0.05).结论 乳房按摩及心理诱导能明显缩短产程,减少产后2h出血量,促进自然分娩,降低剖宫产率及新生儿窒息发生率,提高产科质量和产妇满意度.     

前列腺素E1联合血浆置换治疗慢性重型肝炎的临床研究

目的 探讨前列腺素E1联合血浆置换治疗慢性重型肝炎的疗效.方法 将88例慢性重型肝炎患者完全随机分为治疗组与对照组.治疗组46例,在内科综合治疗的基础上予前列腺素E1联合血浆置换治疗;对照组42例,只予内科综合治疗.观察2组治疗前后的症状体征及相关实验室指标.结果 治疗组经治疗后症状体征均明显好转,总胆红素、ALT、总蛋白、白蛋白、胆碱酯酶、凝血酶原活动度、血氨均改善明显(P＜0.01或P＜0.05).治疗后,2组间除白蛋白水平外,其余各指标均差异有统计学意义(P＜0.05).随访3个月,治疗组总有效率69.6%(32例)、早期有效率79.3%(23例)、中期有效率64.3%(9例),均明显高于对照组的47.6%(20例)、55.6%(15例)、38.5%(5例),差异均有统计学意义(均P＜0.01).结论 前列腺素E1联合血浆置换治疗慢性重型肝炎能明显改善肝功能,明显提高疗效.

Abstract：

Objective To investigate the curative effect, timing and feasibility of prostaglandin E1 combined plasma exchange in treatment of chronic severe hepatitis. Methods Eighty-eight patients with chronic severe hepatitis were randomly divided into treatment group and control group. The treatment group was given prostaglandin E1 combined plasma exchange treatment based on the comprehensive treatment of internal medicine. Control group only had given the internal medicine comprehensive treatment. Results The symptoms and signs of the treatment group were improved after treatments, especially with total bilirubin, cholinesterase, prothrombin activity, NH3 ( P ＜ 0.01,P ＜ 0.05 ). After treatment, except for albumin, the others indicators of the two groups had significant difference ( P ＜ 0.05). Follow-up for three months, the total effective rate of the treatment group was 69.6% ( 32cases ), early effective rate was 79.3% (23 cases), mid-term effective rate was 64.3% (9 cases) were all significantly higher than those of control group [47.6% (20 cases), 55.6% ( 15 cases), 38.5% (5 cases)] (P ＜ 0. 01 ).Conclusion Prostaglandin E1 combined with plasma exchange in treatment of chronic severe hepatitis can improve the liver function and survival rate significantly.