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Japanese Journal of Pharmacology Jul 1984Ritodrine hydrochloride (ritodrine) is a beta 2-adrenoceptor stimulant which has been effectively prescribed for the prevention of premature labor. The present studies...
Ritodrine hydrochloride (ritodrine) is a beta 2-adrenoceptor stimulant which has been effectively prescribed for the prevention of premature labor. The present studies were carried out to investigate the effects of ritodrine on uterine motility in rats and rabbits during gestation, as compared with those of isoproterenol and isoxsuprine. The results were as follows: 1) Spontaneous movements and evoked contractile responses of isolated rat uterus (19-20th days of gestation) were suppressed by 10(-9) - 10(-6) M ritodrine. The potency of ritodrine was approximately 10 times more than that of isoxsuprine and 100 - 1,000 times less than that of isoproterenol. 2) When these drugs were administered to pregnant rats or rabbits intravenously, the tocolytic potency was in the following order: isoproterenol greater than ritodrine greater than isoxsuprine. 3) Ritodrine induced hypotension and tachycardia, but these effects were less than those of isoproterenol and isoxsuprine. 4) The effects of isoproterenol and ritodrine were almost prevented by pretreatment with propranolol, but those of isoxsuprine were only partially or not affected. These results suggest that ritodrine is effective in preventing the uterine contractions in rats and rabbits and that it has less effect on the circulatory system than isoproterenol and isoxsuprine. It is also concluded that ritodrine produces these effects through activation of beta-adrenoceptors.
Topics: Anesthesia; Animals; Blood Pressure; Female; Heart Rate; Isoproterenol; Isoxsuprine; Oxytocin; Pregnancy; Propanolamines; Rabbits; Rats; Rats, Inbred Strains; Ritodrine; Species Specificity; Uterine Contraction
PubMed: 6482092
DOI: 10.1254/jjp.35.319 -
ISRN Obstetrics and Gynecology 2013Aim. Antenatal glucocorticoid therapy (AGT) has been commonly used recently. However, this therapy has severe harmful effects such as maternal hyperglycemia. In Japan,...
Aim. Antenatal glucocorticoid therapy (AGT) has been commonly used recently. However, this therapy has severe harmful effects such as maternal hyperglycemia. In Japan, ritodrine hydrochloride has been used as a tocolytic agent. In this study, we performed retrospective casecontrol study to clarify whether concomitant use of ritodrine and glucocorticoid was safe to pregnant women without diabetes mellitus. Methods. We reviewed the computerized records of pregnant women with pregestational diabetes (n = 9) and nondiabetes (n = 45) who gave birth at our hospital between 2002 and 2011. Cases and controls received AGT. Blood glucose after the therapy was analyzed, and additional volume of insulin was compared to that before the therapy. Results. From this study, 30 units of insulin were necessary when performing AGT in diabetic pregnant women. And also, an increase in blood glucose of 40 mg/dL was seen after the therapy even in nondiabetic pregnant women. Blood glucose increased significantly in the group that also received ritodrine, and it was shown that the number of pregnant women who might develop ketoacidosis might increase 11-fold. Conclusions. Ritodrine should be carefully administered during antenatal glucocorticoid therapy. It may be necessary to adequately monitor blood glucose, when performing the therapy, even in nondiabetic pregnant women.
PubMed: 23533796
DOI: 10.1155/2013/120735 -
PloS One 2023Prematurity is the foremost cause of death in children under 5 years of age. Genetics contributes to 25-40% of all preterm births (PTB) yet we still need to identify...
Prematurity is the foremost cause of death in children under 5 years of age. Genetics contributes to 25-40% of all preterm births (PTB) yet we still need to identify specific targets for intervention based on genetic pathways. This study involved the effect of region-specific non-synonymous variations and their transcript level mutational impact on protein functioning and stability by various in-silico tools. This investigation identifies potential therapeutic targets to manage the challenge of PTB, corresponding protein cavities and explores their binding interactions with intervening compounds. We searched 20 genes coding 55 PTB proteins from NCBI. Single Nucleotide Polymorphisms (SNPs) of concerned genes were extracted from ENSEMBL, and filtration of exonic variants (non-synonymous) was performed. Several in-silico downstream protein functional effect prediction tools were used to identify damaging variants. Rare coding variants were selected with an allele frequency of ≤1% in 1KGD, further supported by South Asian ALFA frequencies and GTEx gene/tissue expression database. CNN1, COL24A1, IQGAP2 and SLIT2 were identified with 7 rare pathogenic variants found in 17 transcript sequences. The functional impact analyses of rs532147352 (R>H) of CNN1 computed through PhD-SNP, PROVEAN, SNP&GO, PMut and MutPred2 algorithms showed impending deleterious effects, and the presence of this pathogenic mutation in CNN1 resulted in large decrease in protein structural stability (ΔΔG (kcal/mol). After structural protein identification, homology modelling of CNN1, which has been previously reported as a biomarker for the prediction of PTB, was performed, followed by the stereochemical quality checks of the 3D model. Blind docking approach were used to search the binding cavities and molecular interactions with progesterone, ranked with energetic estimations. Molecular interactions of CNN1 with progesterone were investigated through LigPlot 2D. Further, molecular docking experimentation of CNN1 showed the significant interactions at S102, L105, A106, K123, Y124 with five selected PTB-drugs, Allylestrenol (-7.56 kcal/mol), Hydroxyprogesterone caproate (-8.19 kcal/mol), Retosiban (-9.43 kcal/mol), Ritodrine (-7.39 kcal/mol) and Terbutaline (-6.87 kcal/mol). Calponin-1 gene and its molecular interaction analysis could serve as an intervention target for the prevention of PTB.
Topics: Humans; Infant, Newborn; Exons; Genes, Regulator; Molecular Docking Simulation; Premature Birth; Progesterone; Polymorphism, Single Nucleotide
PubMed: 36881567
DOI: 10.1371/journal.pone.0280305 -
Circulation Journal : Official Journal... 2013Pregnancy-related acute myocardial infarction (AMI) is uncommon, but can result in maternal and/or fetal death. This study retrospectively reviews pregnancy-related AMI... (Review)
Review
BACKGROUND
Pregnancy-related acute myocardial infarction (AMI) is uncommon, but can result in maternal and/or fetal death. This study retrospectively reviews pregnancy-related AMI reported from medical institutions in Japan.
METHODS AND RESULTS
We electronically or manually searched the literature for reports of pregnancy-related AMI between 1981 and 2011. In total, 62 patients were described and the numbers increased in accordance with the rising average age of the mothers. AMI occurred frequently in women aged 30-34 years (mean age, 33), in the third trimester and postpartum (n=11 and n=28, respectively). The prevalence of conventional risk factors was relatively low (n=21). On the other hand, 29 patients had obstetric and/or non-obstetric complications, and 24 received medication. Only 8 AMI were caused by atherosclerosis, while coronary dissection, thrombus and spasm were the cause in 14, 9 and 12 cases, respectively. All patients with atherosclerosis had conventional risk factors, and some patients with spasm had a history of smoking. Medication with ergot derivatives was associated mostly with spasm, whereas ritodrine was potentially related to dissection.
CONCLUSIONS
The prevalence of pregnancy-related AMI in Japan seems lower than in Western countries, and the etiology differs considerably. However, as the trend of later childbearing continues, more pregnant women have more risk factors, complications, and require medication. Cardiologists and obstetricians must consider the increased risk of AMI.
Topics: Adult; Atherosclerosis; Coronary Disease; Coronary Vasospasm; Disease Management; Female; Humans; Japan; Myocardial Infarction; Pregnancy; Pregnancy Complications, Cardiovascular; Prevalence; Retrospective Studies; Risk Factors; Thrombosis
PubMed: 23182760
DOI: 10.1253/circj.cj-12-1001 -
Anaesthesia Oct 1989
Topics: Adult; Drug Overdose; Female; Humans; Medication Errors; Ritodrine
PubMed: 2589616
DOI: 10.1111/j.1365-2044.1989.tb09118.x -
Reproductive Sciences (Thousand Oaks,... May 2017In recent times, additional pathways involved in the regulation of the myometrium have been suggested. This also holds true for the effect of drugs such as oxytocin (OT)...
In recent times, additional pathways involved in the regulation of the myometrium have been suggested. This also holds true for the effect of drugs such as oxytocin (OT) and β-adrenergic agonists on the myometrium. Knowledge of these additional pathways will certainly prove useful in designing better therapies for pathologies of the myometrium. This study was therefore aimed at investigating the possibility of other pathways involved in the activities of both OT and ritodrine (RIT; a β-adrenergic agonist) in the myometrium by utilizing metabolomics and bioinformatics. High-resolution Fourier transform mass spectrometry (HRFTMS) and nuclear magnetic resonance (NMR) spectroscopy coupled with functional uterine assays were used for an innovative assessment. In vitro pharmacological assay of OT (1 nmol/L) and RIT (0.1 nmol/L) on isolated mice uteri mounted in 3 mL organ baths was performed. Mice uteri, treated with OT or RIT, as well as the physiological buffer in which the uterine tissues were immersed, were rapidly collected and analyzed using HRFTMS, proton (H)-NMR, and bioinformatics. Resulting data were analyzed via pairwise chemometric comparison models, with P ≤ .05 considered statistically significant. In addition to previously known metabolites, nicotinamide adenine dinucleotide, γ-aminobutyric acid, and sphingosine were significantly associated with the activity of OT, whereas the activity of RIT was associated with a downstream involvement of prostaglandin F and phosphatidylinositol signaling. These findings add evidence to the reports on additional regulation of myometrial activity by these drugs and suggest newer pathways for therapeutic manipulation.
Topics: Adrenergic beta-2 Receptor Agonists; Animals; Computational Biology; Female; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolomics; Mice; Mice, Inbred C57BL; Myometrium; Oxytocin; Ritodrine; Signal Transduction; Uterine Contraction
PubMed: 27678101
DOI: 10.1177/1933719116667224 -
The Cochrane Database of Systematic... Jun 2014Preterm birth is a major contributor to perinatal mortality and morbidity, affecting around 9% of births in high-income countries and an estimated 13% of births in low-... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Preterm birth is a major contributor to perinatal mortality and morbidity, affecting around 9% of births in high-income countries and an estimated 13% of births in low- and middle-income countries. Tocolytics are drugs used to suppress uterine contractions for women in preterm labour. The most widely used tocolytic are the betamimetics, however, these are associated with a high frequency of unpleasant and sometimes severe maternal side effects. Calcium channel blockers (CCBs) (such as nifedipine) may have similar tocolytic efficacy with less side effects than betamimetics. Oxytocin receptor antagonists (ORAs) (e.g. atosiban) also have a low side-effect profile.
OBJECTIVES
To assess the effects on maternal, fetal and neonatal outcomes of CCBs, administered as a tocolytic agent, to women in preterm labour.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 November 2013).
SELECTION CRITERIA
All published and unpublished randomised trials in which CCBs were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility, undertook quality assessment and data extraction. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with the 95% confidence interval (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) were calculated for categorical outcomes that were statistically significantly different.
MAIN RESULTS
This update includes 26 additional trials involving 2511 women, giving a total of 38 included trials (3550 women). Thirty-five trials used nifedipine as the CCB and three trials used nicardipine. Blinding of intervention and outcome assessment was undertaken in only one of the trials (a placebo controlled trial). However, objective outcomes defined according to timing of birth and perinatal mortality were considered to have low risk of detection bias.Two small trials comparing CCBs with placebo or no treatment showed a significant reduction in birth less than 48 hours after trial entry (RR 0.30, 95% CI 0.21 to 0.43) and an increase in maternal adverse effects (RR 49.89, 95% CI 3.13 to 795.02, one trial of 89 women). Due to substantial heterogeneity, outcome data for preterm birth (less than 37 weeks) were not combined; one placebo controlled trial showed no difference (RR 0.96, 95% CI 0.89 to 1.03) while the other (non-placebo controlled trial) reported a reduction (RR 0.44, 95% CI 0.31 to 0.62). No other outcomes were reported.Comparing CCBs (mainly nifedipine) with other tocolytics by type (including betamimetics, glyceryl trinitrate (GTN) patch, non-steriodal anti inflammatories (NSAID), magnesium sulphate and ORAs), no significant reductions were shown in primary outcome measures of birth within 48 hours of treatment or perinatal mortality.Comparing CCBs with betamimetics, there were fewer maternal adverse effects (average RR 0.36, 95% CI 0.24 to 0.53) and fewer maternal adverse effects requiring discontinuation of therapy (average RR 0.22, 95% CI 0.10 to 0.48). Calcium channel blockers resulted in an increase in the interval between trial entry and birth (average MD 4.38 days, 95% CI 0.25 to 8.52) and gestational age (MD 0.71 weeks, 95% CI 0.34 to 1.09), while decreasing preterm and very preterm birth (RR 0.89, 95% CI 0.80 to 0.98 and RR 0.78, 95% CI 0.66 to 0.93); respiratory distress syndrome (RR 0.64, 95% CI 0.48 to 0.86); necrotising enterocolitis (RR 0.21, 95% CI 0.05 to 0.96); intraventricular haemorrhage (RR 0.53, 95% CI 0.34 to 0.84); neonatal jaundice (RR 0.72, 95% CI 0.57 to 0.92); and admissions to neonatal intensive care unit (NICU) (average RR 0.74, 95% CI 0.63 to 0.87). No difference was shown in one trial of outcomes at nine to twelve years of age.Comparing CCBs with ORA, data from one study (which did blind the intervention) showed an increase in gestational age at birth (MD 1.20 completed weeks, 95% CI 0.25 to 2.15) and reductions in preterm birth (RR 0.64, 95% CI 0.47 to 0.89); admissions to the NICU (RR 0.59, 95% CI 0.41 to 0.85); and duration of stay in the NICU (MD -5.40 days,95% CI -10.84 to 0.04). Maternal adverse effects were increased in the CCB group (average RR 2.61, 95% CI 1.43 to 4.74).Comparing CCBs with magnesium sulphate, maternal adverse effects were reduced (average RR 0.52, 95% CI 0.40 to 0.68), as was duration of stay in the NICU (days) (MD -4.55, 95% CI -8.17 to -0.92). No differences were shown in the comparisons with GTN patch or NSAID, although numbers were small.No differences in outcomes were shown in trials comparing nicardipine with other tocolytics, although with limited data no strong conclusions can be drawn. No differences were evident in a small trial that compared higher- versus lower-dose nifedipine, though findings tended to favour a high dose on some measures of neonatal morbidity.
AUTHORS' CONCLUSIONS
Calcium channel blockers (mainly nifedipine) for women in preterm labour have benefits over placebo or no treatment in terms of postponement of birth thus, theoretically, allowing time for administration of antenatal corticosteroids and transfer to higher level care. Calcium channel blockers were shown to have benefits over betamimetics with respect to prolongation of pregnancy, serious neonatal morbidity, and maternal adverse effects. Calcium channel blockers may also have some benefits over ORAs and magnesium sulphate, although ORAs results in fewer maternal adverse effects. However, it must be noted that no difference was shown in perinatal mortality, and data on longer-term outcomes were limited. Further, the lack of blinding of the intervention diminishes the strength of this body of evidence. Further well-designed tocolytic trials are required to determine short- and longer-term infant benefit of CCBs over placebo or no treatment and other tocolytics, particularly ORAs. Another important focus for future trials is identifying optimal dosage regimens of different types of CCBs (high versus low, particularly addressing speed of onset of uterine quiescence) and formulation (capsules versus tablets). All future trials on tocolytics for women in preterm labour should employ blinding of the intervention and outcome assessment, include measurement of longer-term effects into early childhood, and also costs.
Topics: Adrenergic beta-Agonists; Calcium Channel Blockers; Female; Humans; Nifedipine; Obstetric Labor, Premature; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Tocolytic Agents
PubMed: 24901312
DOI: 10.1002/14651858.CD002255.pub2 -
Ultrasound in Obstetrics & Gynecology :... Jul 2001To evaluate the effect of ritodrine on the fetal cardiovascular system.
OBJECTIVE
To evaluate the effect of ritodrine on the fetal cardiovascular system.
METHODS
Cardiac and extracardiac Doppler waveforms were recorded in 12 fetuses prior to and during ritodrine therapy used for preterm labor. Maternal and fetal heart rates, the Doppler pulsatility indices of the umbilical artery, middle cerebral artery, descending thoracic aorta and renal artery, and time velocity integrals of the atrioventricular valves and the ductus arteriosus, were measured.
RESULTS
Ritodrine infusion caused an increase in maternal and fetal heart rates, the left cardiac output as measured by the product of time velocity integral and heart rate, and the pulsatility index of the middle cerebral artery, and a decrease in the pulsatility index of the umbilical artery.
CONCLUSIONS
Ritodrine infusion may alter placental and cerebral blood flow and may have a selective effect on the left side of the heart.
Topics: Cardiac Output; Cardiovascular System; Cerebrovascular Circulation; Female; Fetus; Heart Rate; Hemodynamics; Humans; Placenta; Pregnancy; Regional Blood Flow; Ritodrine; Sympathomimetics; Tocolytic Agents
PubMed: 11489225
DOI: 10.1046/j.1469-0705.2001.00453.x -
JA Clinical Reports 2017Since acute respiratory failure (ARF) is a life-threatening complication, particularly in the gestational period, differential diagnosis and rapid treatment are...
BACKGROUND
Since acute respiratory failure (ARF) is a life-threatening complication, particularly in the gestational period, differential diagnosis and rapid treatment are required. Among the various causes of sudden onset of ARF, thyroid storm is a rare cause in a parturient complicated with well-controlled hyperthyroidism. In this case report, we describe a parturient with hyperthyroidism in whom a thyroid storm manifesting congestive heart failure and pulmonary edema developed just before an emergency ceasarean section, even though hyperthyroidism was well-controlled with antithyroid drugs.
CASE PRESENTATION
A 36-year-old pregnant woman was diagnosed as having clinical chorioamnionitis, and an emergency cesarean section was performed at 25 weeks of pregnancy. She had a complication of hyperthyroidism accompanied by mild mitral regurgitation, and she had been treated with methimazole. She was treated with ritodrine and MgSO for the threat of premature delivery. At the preoperative consultation, her percutaneous oxygen saturation (SpO) was 98% on room air. When she was admitted to the operating room, her heart rate and blood pressure were 130 beats/min and 196/78 mmHg, respectively. SpO was 88% on room air without any symptoms; however, just after starting oxygen administration via a facemask, she complained of severe respiratory distress and became agitated. Partial pressure of arterial oxygen was 108 mmHg with an inspiratory oxygen fraction of 1.0. Chest radiography revealed pulmonary congestion, and transesophageal echocardiography revealed normal right ventricular function without an embolus and severe mitral regurgitation with preserved left ventricular function. Contrast-enhanced computed tomography after the operation revealed no pulmonary embolus but revealed a pulmonary effusion, and free triiodothyronine level was increased at the onset of dyspnea. Therefore, we diagnosed the causes of sudden onset of dyspnea as pulmonary edema and congestive heart failure induced by a thyroid storm.
CONCLUSION
Sudden onset of a thyroid storm just before a cesarean section occurred in a patient with several risk factors of thyroid storm and pulmonary edema, including pregnancy, treatment with tocolytic agents, and infection. The involvement of these multiple factors was considered to be the cause of the sudden onset of the thyroid storm and the cause of rapidly progressive pulmonary edema.
PubMed: 29457064
DOI: 10.1186/s40981-017-0088-3 -
Anesthesiology Feb 1990The purpose of this study was to determine whether prior administration ritodrine worsens maternal hypotension during epidural anesthesia in gravid ewes. Twenty-four...
The purpose of this study was to determine whether prior administration ritodrine worsens maternal hypotension during epidural anesthesia in gravid ewes. Twenty-four experiments were performed in nine chronically instrumented animals between 0.8 and 0.9 of timed gestation. The experimental sequence included the following: 1) at time-zero, intravenous (iv) administration of ritodrine, 0.004 mg.kg-1.min-1, or normal saline (NS) for 2 h; 2) at 120 min discontinuation of ritodrine, and administration of a 500 ml iv bolus of NS over 15 min; and 3) at 135 min epidural injection of 2% lidocaine or NS. There were three groups of experiments: 1) iv ritodrine-epidural lidocaine (n = 9); 2) iv NS-epidural lidocaine (n = 8); and 3) iv ritodrine-epidural NS (n =7). Epidural injection of lidocaine resulted in a median sensory level of T9 in both the ritodrine-lidocaine and NS-lidocaine groups. At 165 min (i.e., 30 min after the epidural injection of lidocaine), maternal mean arterial pressure was 19 +/- 3% below baseline (P = 0.0001) in the ritodrine-lidocaine group and 22 +/- 7% below baseline (P = 0.0001) in the NS-lidocaine group (NS between groups). At 120 min ritodrine had increased maternal cardiac output 45 +/- 6% above baseline (P = 0.0001) in the ritodrine-lidocaine group and 39 +/- 6% above baseline (P = 0.0001) in the ritodrine-NS group. Cardiac output remained above baseline (P less than 0.01) after epidural injection of lidocaine in the ritodrine-lidocaine group. In contrast, in the NS-lidocaine group cardiac output was 13 +/- 5% below baseline (P = 0.005) at 150 min. Fetal arterial pH did not change significantly in either the ritodrine-lidocaine or ritodrine-NS group.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Anesthesia, Epidural; Anesthesia, Obstetrical; Animals; Drug Interactions; Female; Heart Rate, Fetal; Hemodynamics; Hypotension; Lidocaine; Pregnancy; Ritodrine; Sheep
PubMed: 2301763
DOI: 10.1097/00000542-199002000-00018